Wesley Thevathasan Fracp

Patrick Schweder Mbchb

PhD Carole Joint

Nicola Ray Dphil

Pieter Pretorius Frcr

FRCP Ralph Gregory

Tipu Aziz Frcs

Dr Wesley Thevathasan
email: wesley.thevathasan@nds.ox.ac.uk

Permanent tremor reduction during thalamic stimulation in Multiple Sclerosis

Keywords: Multiple sclerosis, Demyelination, Tremor, Thalamic, Stimulation

Background: Unlike thalamic lesioning, thalamic stimulation is considered a reversible treatment for tremor. However, tremor in Multiple Sclerosis (MS) can sometimes permanently improve during thalamic stimulation. Such 'permanent tremor reduction' (PTR) has been attributed to limb weakness preventing tremor expression.

In this study, eleven consecutive patients with MS tremor treated with thalamic stimulation were assessed for PTR. Eighteen upper limbs had tremor, of which sixteen received contralateral stimulation.

Methods:

Tremor severity and limb strength were assessed preoperatively, early postoperatively (within one year) and late postoperatively (after three years). Tremor severity was rated using validated clinical scales both on and off stimulation. Following explantation, the parenchyma surrounding three electrode tracts was examined with MRI.

Results: At final review (mean 5.2 years) PTR was evident in eleven of the eighteen upper limbs with tremor. PTR often rendered stimulation redundant. PTR could occur when limb strength was conserved and could arise remotely from the initial surgery. PTR was significant (and universal) in limbs that received long term (>2 years), effective (tremor suppressing) stimulation. PTR was not a significant finding in limbs that had not received long term, effective stimulation. Contralateral to a limb with PTR, MRI revealed a thalamic lesion adjacent to the electrode tract. Thalamic lesions were not identified contralateral to two limbs without PTR.

Conclusions: MS tremor often permanently improves during thalamic stimulation, even when limb strength is conserved. PTR may simply reflect natural history. Alternatively, our Thevathasan 3 findings appear consistent with the recent proposal that thalamic stimulation in MS might promote local "demyelinative lesioning".

Introduction

Thalamic lesioning and thalamic deep brain stimulation (DBS) are therapeutic options for severe, medication refractory tremor in multiple sclerosis (MS). [START_REF] Brice | Suppression of intention tremor by contingent deep-brain stimulation[END_REF][START_REF] Alusi | Stereotactic lesional surgery for the treatment of tremor in multiple sclerosis: a prospective case-controlled study[END_REF] Whereas lesioning is permanent, stimulation is acutely reversible. For example, switching off thalamic stimulation should result in 'rebound' of tremor to pre-stimulation amplitudes.

However, it has been observed that tremor in MS can sometimes permanently reduce during the course of chronic thalamic stimulation. [START_REF] Moringlane | Improvement of upper limb ataxia and intention tremor allowing cessation of thalamic electrostimulation after four years[END_REF][START_REF] Hyam | Post-deep brain stimulation--gradual non-stimulation dependent decrease in strength with attenuation of multiple sclerosis tremor[END_REF] Hitherto, this permanent tremor reduction (PTR) has been attributed to limb weakness (occurring with MS disease progression) preventing the expression of tremor. [START_REF] Hyam | Post-deep brain stimulation--gradual non-stimulation dependent decrease in strength with attenuation of multiple sclerosis tremor[END_REF] In this study, we assessed a consecutive cohort of patients with MS tremor treated with long term thalamic stimulation. Tremor severity was rated both on and off stimulation over time.

Tremor scores were correlated with limb strength and the duration and effectiveness of stimulation.

Methods

Subjects

The study group comprised sixteen consecutive upper limbs with MS tremor treated with contralateral thalamic stimulation in eleven patients. Additionally there were two upper limbs Thevathasan 4 with tremor that did not receive stimulation (two patients had bilateral tremor but received only unilateral stimulation). Surgery was performed by the same surgeon (TA) at least three years previously (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)) at a single centre (Oxford).

All patients met diagnostic criteria for MS and had severe medication refractory tremor.

Baseline clinical features were as follows (Mean±SD).; Age 38.7±11 years; 8 female, 3 male; MS duration 12.2±7.4 years; Extended Disability Status Score (EDSS) 7.2±1.1 . In all cases, tremor was predominant in the upper limbs and occurred with posture and action. No patient had rest tremor. Seven patients had bilateral tremor and four unilateral.

Under local anaesthesia, quadripolar electrodes (Model 3387, Medtronic) were inserted into the ventral oralis posterior (VOP) nucleus of the thalamus and zona incerta (ZI), as described previously. [START_REF] Nandi | Deep brain stimulation in the management of neuropathic pain and multiple sclerosis tremor[END_REF] Positioning was confirmed on postoperative CT fused with preoperative MRI.

Stimulation parameters were as follows (Mean±SD); frequency 130Hz or 180Hz, pulse width 216±99 usec, voltage 3.8±1.2v. There were no acute infective or haemorrhagic complications. In one patient, the DBS system was removed due to persistent scalp erosion over the extension cables. One patient experienced self limited focal seizures in the immediate postoperative period without an identifiable structural lesion on imaging.

Clinical assessments

Tremor severity was assessed preoperatively, early postoperatively (within twelve months) and late postoperatively (after at least 3 years).

Assessments were performed both on and off stimulation using clinical scoring methods specifically validated for MS tremor; the Clinical Rating Scale (CRS) and grading an Thevathasan 5 Archimedes spiral drawing. [START_REF] Alusi | Evaluation of three different ways of assessing tremor in multiple sclerosis[END_REF] CRS was rated during posture (P-CRS, score/10) and movement (M-CRS, score/10) then summated to yield the total CRS score (T-CRS, score/20). Discriminating between action and intention components of movement related tremor is poorly reliable and was therefore not performed. [START_REF] Alusi | Evaluation of three different ways of assessing tremor in multiple sclerosis[END_REF] Archimedes spiral drawings (by the dominant hand, if stimulated) were graded (score/10), with higher scores indicating a worse spiral. Tremor was assessed unblinded from videotape recordings by a neurologist specialised in movement disorders (WT). Off stimulation assessments occurred at least 20 minutes after stopping stimulation, a period shown to be sufficient for >90% of Parkinsonian tremor to return following cessation of stimulation. [START_REF] Temperli | How do parkinsonian signs return after discontinuation of subthalamic DBS?[END_REF] Upper limb strength was scored using the Medical Research Council (MRC) scale (score/5).

The average of the MRC scores for shoulder abduction and finger extension was calculated for each upper limb. This method was used to capture weakness relevant to the expression of proximal and distal upper limb tremor, as utilised previously in the assessment of MS tremor during DBS. [START_REF] Hyam | Post-deep brain stimulation--gradual non-stimulation dependent decrease in strength with attenuation of multiple sclerosis tremor[END_REF] Local ethics committee approval was obtained and participants gave informed consent.

Radiological assessments

MRI was performed to assess the parenchyma adjacent to electrode tracts. In subjects with DBS systems in situ, the artefact associated with the electrodes prevented useful assessment of the immediately surrounding parenchyma. We therefore limited MRI assessments to those where DBS systems had been explanted.

The imaging protocol included axial fluid attenuated inversion recovery (FLAIR) and T2weighted sequences acquired on a Philips Achieva® 1.5 Tesla Magnet (see supplementary Thevathasan 6 material). Electrode tracts were identified in cross section on axial views and if required, longitudinally on coronal and sagittal reconstructions of the axial images.

The distal 12mm of the Medtronic 3387 electrode contains the 1.5mm inactive tip and four 1.5mm contacts (spaced 1.5mm apart) through which stimulation can be delivered. However, termination of the tract signal on MRI could not be assumed to reflect the position of the electrode tip during stimulation as electrode depth was often adjusted in theatre before securing the final position. We therefore conservatively estimated that stimulation could have been delivered up to 30mm proximal to tract termination.

Lesion localisation was performed if appropriate using stereotactic planning software (Radionics, MS, USA) to calculate Cartesian coordinates relative to the Anterior Commissure-Posterior Commissure (AC-PC) plane and referencing to the histological Schaltenbrand-Wahren atlas.

Results

Clinical assessments

Early (<1 year) postoperative outcomes

For the sixteen limbs that received contralateral stimulators, the mean T-CRS improved by 44% with stimulation (14.8 to 8.3, Wilcoxon p=0.002, z =-3.063) (table 2). However, the response to stimulation was variable and improvements in T-CRS ranged from 0-86%. In four upper limbs (of two patients), T-CRS and spiral scores did not improve with stimulation, however stimulation was continued due to subjective benefits. Six patients regained the ability to drink from a cup or beaker from a tremulous limb.

Thevathasan 7

In the early postoperative period, tremor severity was also assessed in five upper limbs after switching stimulation off. In four of these, the T-CRS scores 'off stimulation' were identical to preoperative scores. In one limb, the off stimulation T-CRS score was lower than the preoperative score, but stimulation remained beneficial.

Late (> 3 years) postoperative outcomes

By final review (5.2±1.8 years), PTR had developed in ten of the sixteen upper limbs that received contralateral stimulation. In eight, T-CRS scores 'off stimulation' were even less than their previous 'on stimulation' scores (from the early postoperative period). PTR was often not recognised. In many cases, stimulation had become redundant and batteries had depleted without the patient noticing. In six limbs PTR was observed despite stimulation having ceased over a year previously (a finding inconsistent with PTR being simply due to delayed 'washout' of stimulation).

All ten upper limbs that developed PTR during DBS had received long term (>2 years) and effective (tremor score suppressing) stimulation. In two, it was possible that severe weakness (MRC=2) was preventing tremor expression. However, PTR remained a significant finding in the remaining eight limbs where limb strength had been conserved (MRC≥4), (mean T-CRS 13.6 Vs 5.2, Wilcoxon p=0.012, z=-2.527) (table 2, figure 1a).

Six upper limbs that received contralateral stimulation did not develop PTR. However, none of these six limbs had received effective, long term stimulation. In four (two patients), stimulation had been ineffective (could not suppress tremor scores). Two upper limbs (one patient) had received effective stimulation but after a year the DBS system had to be removed (due to scalp erosion over the extension cables) and tremor rebounded to preoperative levels Thevathasan 8 and persisted to final follow up (at 5 years). Additionally, there were two upper limbs with tremor that did not receive a contralateral stimulator (in patients with bilateral tremor but unilateral stimulators) -tremor reduced in one and worsened in the other. There were, therefore, a total of eight limbs with tremor that did not receive long term, effective stimulation (table 2, figure 1b). For this group, off stimulation T-CRS scores were not significantly different to preoperatively (mean 13.8 Vs 13.4, Wilcoxon p=0.593, z= -0.535).

Of the five limbs that were assessed 'off stimulation' in the first postoperative year, PTR ultimately developed in three. In two, PTR had developed wholly after that first assessment.

In one limb, PTR had progressed since the first assessment.

Radiological assessments

DBS hardware was removed following thalamic stimulation in two patients (patients 3 and 6), permitting MRI assessment of three electrode tracts (figure 2). In both cases, MRI disclosed extensive (>30) white matter lesions with morphology, signal characteristics and distribution consistent with MS. Patient 3 had left thalamic stimulation for unilateral right sided tremor. Monopolar stimulation was applied through the lowest contact at 130Hz/2.7Volts/90usec. After 3.8 years, PTR developed and stimulation became unnecessary. The DBS system was explanted on the patient's request. On MRI, the electrode tract could not be definitively identified along its course through white matter. However tract signal was identified in the thalamus as a discrete, sharply demarcated hyperintensity of approximately 1.5mm diameter on T2 and FLAIR images. Cartesian coordinates for this location corresponded to the motor thalamus (at the junction of VIM and VOP) on the Schaltenbrand-Wahren atlas. Directly adjacent to, Thevathasan 9 and partially surrounding the tract, a small area of slightly less markedly elevated signal was evident on both T2 and FLAIR images (fig 2a andb). This lesion measured 5mm x 4mm x 6mm in XYZ planes. The lesion was not present on preoperative imaging. Patient 6 had bilateral tremor successfully suppressed with bilateral DBS. Bipolar stimulation had been applied at 130Hz/330usec bilaterally, left 3.2volts and right 3.4volts. After 1 year the DBS system was removed due to hardware complications and tremor recurred. On T2 and FLAIR, electrode tracts appeared as well defined hypointense signal intensities passing from frontal gyral cortex through white matter and lateral thalami. Due to severe ventricular dilatation and substantial atrophy, atlas based localisation was not appropriate. Inspection of brain parenchyma surrounding the distal 30mm of the tract (including the thalami) did not reveal any neighbouring focal white matter lesions (figure 2c). Elsewhere, both electrodes did traverse regions of widespread demyelination, however discrete focal demyelination adjacent to tract signal was not observed.

Discussion

In this study, we found that it is common for MS tremor to permanently improve during long term thalamic stimulation. Permanent tremor reduction occurred even when limb strength had been conserved. This suggests that tremor itself diminished rather than the expression of tremor being prevented by severe weakness, as had been suggested previously. [START_REF] Hyam | Post-deep brain stimulation--gradual non-stimulation dependent decrease in strength with attenuation of multiple sclerosis tremor[END_REF] Permanent reduction of MS tremor during DBS may simply reflect natural history. For example, we observed PTR in a limb that had not received any contralateral stimulation.

However, spontaneous remission of MS tremor is not reported to be common. For example, in a study of 100 outpatients with MS, 31 had tremor and none reported tremor remission. [START_REF] Alusi | A study of tremor in multiple sclerosis[END_REF] Thevathasan 10

Another possibility is that DBS promotes PTR. For example, electrode implantation can cause a 'persistent microthalamotomy'. However, we observed PTR to begin or progress after the first postoperative assessment. This leaves open the possibility that chronic DBS elements may promote PTR, such as the presence of implanted electrodes or the electrical stimulation.

Accordingly, PTR was found to be significant following long term, effective stimulation but not with short term or ineffective stimulation.

The first pathological study of a patient with MS tremor treated with thalamic stimulation has recently been reported. [START_REF] Moore | Thalamic stimulation in multiple sclerosis: evidence for a 'demyelinative thalamotomy[END_REF] In the thalamus on post mortem, focal demyelination was detected between the electrode cathode and anode, diminishing with distance from the centre of the electrical field. The authors postulated that electrical stimulation could have contributed to demyelination at that site, causing a thalamotomy. This lesioning hypothesis would be consistent with the time course of PTR that we observed. Additionally, it would explain why PTR occurred when stimulation had been effective (suppressed tremor), as tremor reduction from lesioning can be predicted by tremor suppression from stimulation. [START_REF] Hassler | The influence of stimulations and coagulations in the human thalamus on the tremor at rest and its physiopathologic mechanism[END_REF] In MS tremor, there is a variable contribution of ataxia to the overall tremor phenotype. [START_REF] Liu | Frequency analysis of involuntary movements during wrist tracking: a way to identify ms patients with tremor who benefit from thalamotomy[END_REF][START_REF] Liu | Analysis of action tremor and impaired control of movement velocity in multiple sclerosis during visually guided wrist-tracking tasks[END_REF]Ataxic tremor responds poorly to both stimulation and lesioning -potentially explaining why MS tremor responds so variably to stimulation and why four limbs failed to achieve tremor suppression with DBS and subsequently failed to develop PTR. [START_REF] Liu | Frequency analysis of involuntary movements during wrist tracking: a way to identify ms patients with tremor who benefit from thalamotomy[END_REF][START_REF] Liu | Analysis of action tremor and impaired control of movement velocity in multiple sclerosis during visually guided wrist-tracking tasks[END_REF] In the absence of pathological findings from patients in this study, we assessed the parenchyma surrounding electrode tracts with MRI (in cases where DBS systems had been explanted). We caution that the MRI findings are not conclusive. However the findings do appear consistent with stimulation associated lesioning. Two limbs had not developed PTR and contralateral thalamic lesions were not seen. One limb had developed PTR and a lesion was evident in the contralateral motor thalamus, adjacent to the tract of the stimulating Thevathasan 11 portion of the electrode. Thalamic demyelination is known to occur spontaneously in MS. [START_REF] Vercellino | Grey matter pathology in multiple sclerosis[END_REF] Whether such lesioning might be further promoted by DBS needs further research.

Clinically, the PTR phenomenon is important to recognise. We would recommend that the persistence of tremor 'off stimulation' should be determined, to avoid unnecessary replacement of batteries nearing depletion.

Ethical approval Ethical approval was obtained from the local ethics committee and patient consent was obtained.

Funding No external funding

Competing Interests: TA has received research funding and honoraria from Medtronic and St Jude's Medical.

Licence for Publication:

The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article (if accepted) to be published in the Journal of Neurology, Neurosurgery & Psychiatry editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence (http://jnnp .bmjjournals.com/ifora/licence.pdf).

Figure 2 :

 2 Figure 2: Axial MRI images of patient 3 (2a and 2b) and patient 6 (2c) following

Table 1 :

 1 Early 'on stimulation' outcomes for the sixteen upper limbs of eleven patients that received contralateral DBS. Mean±SD(range). ** Dominant hand unless only the non dominant hand received contralateral DBS. * P<0.05; ⁺P<0.01

				Able to drink from a
		T-CRS score /20	Spiral score /10
		(stimulated limbs)	(dominant hand)**	beaker	EDSS /10
		N=16	N=11	(from limb receiving DBS)
				N/11
	Preoperative	14.8 ± 2.5 (9-18)	8.6 ± 2.1 (5-10)	0/11	7.2 ± 1.1 (6-9)
	Early Postoperative
		8.3 ± 4.9 (2-17)⁺	6.4 ± 2.5 (4-10)*	6/11*	7.0 ± 1.0 (5.5-8.5)
	(On Stim)

Table 2 :

 2 Comparison of tremulous upper limbs with preserved strength that received long term effective stimulation and those that did not. Mean±SD(range). Differences between final and initial cores *P<0.05 (Wilcoxon). There were no significant differences in mean follow up, initial or final MRC scores or initial T-CRS scores between the two groups (independent samples t test). T-CRS scores of the 18 upper limbs with MS tremor (16 received contralateral stimulators and 2 did not). Timepoints are; preoperative baseline, one year postoperatively (on contralateral stimulation, if present) and long term follow up (off stimulation). 1a; Upper limbs with tremor that received effective, long term stimulation. 1b; Upper limbs with tremor that did not receive effective, long term stimulation.

	Thevathasan 14

Acknowledgements: This work was supported by: The Oxford Biomedical Research Centre, The Medical Research Council, UK, The Charles Wolfson Charitable Foundation and the Norman Collisson Foundation. Thevathasan 12


M.D Juergen Brunner
email: juergen.brunner@uki.at

Martin Herrmann

Markus Metzler

Udo Gaipl

Gert Reuter

Johannes-Peter Haas

The turnover of synovial T cells in persistent oligoarticular Juvenile Idiopathic Arthritis is higher than in T cells in the peripheral blood

Keywords: cell cycle, juvenile idiopathic arthritis, S-phase, proliferation Cell cycle of T cells

Introduction: Juvenile idiopathic arthritis (JIA) summarizes a group of inflammatory diseases of childhood. The etiology remains still unclear. In JIA T cells have been demonstrated to play key roles in the pathogenesis. T-cell proliferation in JIA may be different in the peripheral blood (PB) and the synovial fluid (SF). The aim of this study is to demonstrate the turnover of T-cells in the PB and SF of patients with persistent oligoarticular JIA (oJIA) compared to controls.

PATIENTS AND METHODS

Matched pairs of samples were investigated derived from PB and synovial fluid SF of 9 patients with persistent oJIA. The cells from PB and SF were determined by flow cytometry.

RESULTS

The majority of the PBMC and IAMC were in phase G0/G1, with fewer than 1% in S phase. In the SF the percentage of cells in the S phase is higher than in the PB. The percentage of cells in the S phase in SF is equal to the result in the control group. In conclusion the turnover of synovial T-cells in persistent oJIA is higher than in the PB.

INTRODUCTION

Juvenile idiopathic arthritis (JIA) summarizes a group of phenotypically heterogeneous chronic inflammatory diseases of childhood involving joints as well as extraarticular tissues. There are seven subtypes of JIA defined according to clinical classification criteria (9;10). Genetic factors, especially certain HLA-alleles have been shown to contribute to the susceptibility and have been additionally proposed to be involved in the pathogenesis of JIA [START_REF] Haas | Susceptible and protective major histocompatibility complex class II alleles in early-onset pauciarticular juvenile chronic arthritis[END_REF]. It has been supposed that HLA-alleles might present certain peptides thus shaping an autoreactive T-cell repertoire. The trimolecular complex of the MHC-molecule, the presented peptide and the T cell receptor (TCR) is one of the most important molecular interactions in the activation cascade leading to specific immunity (5;18). Stimulation with an antigen via the HLA presenting cell leads to stimulation of T-cells carrying a TCR specific for the peptide/HLA combination. These T cells will subsequently proceed to expansion (1;16). In JIA T cells have been demonstrated to play key roles, both for induction and maintenance of the chronic inflammation (4;17). Diminished mechanisms of Tcell homeostasis and premature aging of the immune system may play a role in the pathogenesis and perpetuation of chronic inflammation in JIA [START_REF] Prelog | Premature aging of the immune system in children with juvenile idiopathic arthritis[END_REF][START_REF] Prelog | Indications for a disturbed peripheral T-cell homeostasis in juvenile idiopathic arthritis (JIA): absent expansion of CD28 T-cells and no decrease of naive T-cells in cytomegalovirus-positive patients with JIA[END_REF][START_REF] Prelog | Quantitative alterations of Cell cycle of T cells in in JIA Rheumatology International January 2010 10 CD8(+) T cells in juvenile idiopathic arthritis patients in remission[END_REF]. T-cells in the peripheral blood (PB) and the synovial fluid (SF) of patients with rheumatoid arthritis (RA) have a higher proportion of actively synthesizing DNA (S-phase) cells than the T-cells in controls [START_REF] Russell | Activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis[END_REF]. The aim of this study is to demonstrate the turnover of T-cells in the PB and SF of patients with persistent oligoarticular JIA (oJIA) compared to controls.

PATIENTS AND METHODS

Matched pairs of samples were investigated derived from PB and synovial fluid SF of 9 patients (3 males, 6 females, mean age 8.6 years) with persistent oJIA with active arthritis (table 1). Diagnosis of JIA was based on the revised ILAR criteria [START_REF] Petty | Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997[END_REF]. Other causes of arthritis as infections or malignancy have been excluded. All patients diagnosed with persistent oJIA were seen at two tertiary care centers and underwent clinical standardized assessment [START_REF] Petty | Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997[END_REF] Cell cycle of T cells in in JIA Rheumatology International January 2010

6

RESULTS

The majority of the PBMC and IAMC were in phase G0/G1, with fewer than 1% in S phase (figure 1). In the SF the percentage of cells in the S phase is higher than in the PB (in promille) (p < 0.05) of oJIA patients and NHD (table 2). The percentage of cells in the S phase in SF is equal to the result in the control group. The percentage of cells in the G2 phase is higher in the PB of patients with persistent oJIA than in NHD (p>< 0.0936).

DISCUSSION

This is the first study investigating the cell cycle analysis of T-cells in the PB and SF

of patients with persistent oJIA. The turnover of T-cells in the SF is higher than in the PB of oJIA patients (p < 0.05) and similar to the turnover of T-cells in NHD. Therefore a local proliferation in the SF may be considered. Other results were contradictory: Tcell proliferation was no greater in SF than in PB (2;3). Regarding the observation of expression of activation markers the findings suggest that SF T-cells in JIA are activated without proliferation [START_REF] Black | T-cell activation without proliferation in juvenile idiopathic arthritis[END_REF]. In RA the PB and SF has a higher proportion of Sphase cells compared to controls (8;14). However, regarding our own results, it may be possible, that small numbers of SF T-cells are driving an intraarticular inflammatory process due to an expansion of antigen-specific T cells within the joint [START_REF] Sieper | T cells are responsible for the enhanced synovial cellular immune response to triggering antigen in reactive arthritis[END_REF]. The proliferation in the PB in oJIA is reduced. Medical treatment may decrease the percentage of S-phase cells [START_REF] Julis | DNA microfluorometry of synovial effusion cells in rheumatic diseases[END_REF]. In conclusion the turnover of synovial T-cells in persistent oJIA is higher than in PB. Considering the small number of patients, further studies are necessary to correlate cell cycle analysis with T-cell activation markers.

  . Joint punctions have been performed for diagnostic and/or therapeutic reasons exclusively. The study was performed according to the declaration of Helsinki 2000 and approved by the local ethics committee, Friedrich-Alexander University Erlangen Nuremberg. All patients and/or their parents had been given their written informed consent. The controls are from adult normal healthy donors (NHD). Laboratory analyses included blood cell count and C-reactive protein. All results were in normal range. All patients were treated with non steroidal anti-inflammatory drugs (NSAID) and/or methotrexate. Peripheral blood mononuclear cells (PBMC) from peripheral blood (5-10ml, heparinized blood) and intraarticular mononuclear cells (IAMC) from SF (10ml anticoagulated with heparine) were prepared according to standard procedures (Lymphoprep, Nycomed Pharma AS, Asker, Norway). SF was filtered through a 100nm nylon filter and centrifuged. The cell pellet was resuspended in RPMI-1640 medium. Cell-cycle analysis on CD3+ T-cells was performed by propidium iodid staining. Immunofluorescence was determined by flow cytometry (Beckman-Coulter EPICS Elite ESP Sorter, Canada). Dead cells were excluded by gating on forward/side scatter and T cells were selected by gating CD3+ cells. Results were Cell cycle of T cells in in JIA Rheumatology International January 2010 5 expressed as the percentage of gated lymphocytes. The t-test for independent variables was used to compare results in PB and SF (SPSS version 15.0; SPSS,Chicago, IL).

Figure 1 :

 1 Figure 1: Cell cycle analysis of intraarticular mononuclear cells (IAMC) from a

Table 1 :

 1 Characteristics of the investigated patients with persistent oligoarticular juvenile idiopathic arthritis (oJIA). Most of the patients had antinuclear antibodies (ANAs).

	no	sex	age (y)	diagnosis	ANA	uveitis	medication
	1	f	2	oJIA	positive	no	NSAID
	2	m	12	oJIA	positive	no	NSAID
	3	m	5	oJIA	negative	no	NSAID
	4	f	4	oJIA	positive	no	NSAID
	5	f	8	oJIA	positive	no	NSAID
	6	f	16	oJIA	positive	no	NSAID
	7	m	12	oJIA	positive	no	NSAID
	8	f	10	oJIA	positive	no	NSAID, MTX
	9	f	8	oJIA	positive	no	NSAID

Table 2 :

 2 Cell cycle analysis of T cells of the peripheral blood (PB) and from the synovial fluid (SF) of patients with persistent ologoarticular juvenile idiopathic arthritis (oJIA). Most of the T-cells are in G0/G1 phase. In the SF the percentage of cells in the S phase is higher than in the PB (in promille) (p < 0.05). The two numbers in bold mark the most relevant results.

			all	apoptosis	apoptosis	S phase	S phase	G0/G1 phase	G0/G1 phase
	Patient sample	events	(cells)	(o/oo)	(cells)	(o/oo)	(cells)	(o/oo)
	1	PB	18315	100	5,48	113	6,19	17996	986,35
	1	SF	25142	228	9,14	196	7,86	24370	976,99
	1	SF	25552	125	4,98	193	7,69	24465	975,17
	2	PB	40826	129	3,16	278	6,80	40303	986,54
	2	SF	33540	43	1,28	65	1,94	33394	995,53
	3	PB	33983	612	18,07	81	2,39	33081	976,85
	3	SF	16072	353	21,81	102	6,30	15656	967,49
	4	PB	15639	198	12,66	34	2,17	15372	982,80
	4	SF	21863	209	9,56	214	9,79	21389	978,10
	5	PB	24544	902	36,87	126	5,15	23381	955,65
	5	SF	4710	269	59,19	15	3,30	4254	935,97
	6	PB	18042	408	22,52	37	2,04	17629	973,23
	6	SF	17158	183	10,64	97	5,64	16880	981,34
	7	PB	13869	386	27,57	50	3,57	13523	965,93
	7	SF	24811	322	12,95	232	9,33	24246	975,11
	7	SF	23035	138	6,00	75	3,26	22728	988,86
	8	PB	21071	64	3,06	5	0,24	20285	970,71
	8	SF	33128	290	8,94	89	2,74	31811	980,28
	9	PB	21411	426	20,84	28	1,37	19479	952,98
	9	SF	23840	721	31,76	103	4,54	21115	930,01
	Mean	PB	23077	358	16,69	83,56	3,32	22338	972,33
	Mean	SF	22622	261	16,02	125,55	5,67	21846	971,35
	Mean	NHD	19546	456	24,40	108	7,72	18944	966,00

ACKNOWLEDGEMENT

The authors declare that they have no conflict of interest.


Monique Koemans

The war on street 'terror'. Why tackle anti-social behaviour?

This article examines the rationales of Dutch politicians for tackling the perceived pressing problem of 'anti-social behaviour' (ASB) and the question did they copy the British approach? The first part will describe in short the concept of policy transfer and the recent British fight against ASB. The focus will be on the introduction of the Anti-social Behaviour Order. The second part is an empirical study into the Dutch retreat from 'condoning' ASB, consisting of interviews with Dutch politicians focusing on their ideas for tackling ASB. Those are compared with the British's rationales. This kind of comparative elite ethnography is not common in criminology, but this article aims at providing evidence of its benefits. By answering the research question an insight into the origins of policy in the sphere of criminal justice can be obtained.

Introduction

On September 14, 2008 the problem of anti-social behaviour (henceforth ASB) became front-page news in the Netherlands. In Gouda1 several bus drivers refused to drive through a certain neighbourhood any longer, because of the ASB they encountered on their daily rounds. Especially young Moroccans were accused of terrorising the public transport routes. Their ASB in the form of yelling, spitting at other passengers and intimidating the bus drivers was no longer tolerated. The situation escalated when television journalists were threatened by the youngsters. A Dutch politician claimed the neighbourhood had turned into a 'no-go area'. 2As a result an emergency debate in Dutch parliament on the problem of ASB was called. During the heated political discussion, nuisance in the public domain 3 was labelled an 'acute problem' that pressed for 'a quick and harsh response'. This Gouda-debate generated some remarkable media quotes; 'ASO-terror damages public transport', 'Send the army', 'tough actions needed against street terror', 'tackle street terror today, not tomorrow', and 'anti-social behaviour wreaks serious havoc in many Dutch cities'. 4 Although the perceived problem of ASB by Moroccan youth has been on the Dutch societal agenda for the last six to eight years, now (after recent incidents like Gouda) it appears more acute.

Of course ASB is hardly a new phenomenon [START_REF] Ramsay | Vulnerability, sovereignty and police power: A theory of the ASBO[END_REF][START_REF] Van Weringh | Onrust is van alle tijden. Opstellen over criminaliteit in Nederland[END_REF]. Twenty years ago nuisance in the public domain was a reality as well. But in those days, the byword was to condone (turning a blind eye) [START_REF] Devroe | The policy approach of nuisance problems in public space in Belgium and the Netherlands[END_REF]. But nowadays ASB has become a major policy preoccupation and it is directly connected to the problems of young immigrants from Morocco [START_REF] Punch | Paradigm lost: the Dutch dilemma[END_REF]. For many Dutch politicians it is now self-evident that the government should act firm against ASB [START_REF] Koemans | Ten strijde tegen overlast[END_REF][START_REF] Pakes | De Britse aanpak van antisociaal gedrag[END_REF][START_REF] Van Stokkom | Regulering van antisociaal gedrag. Aanpak van persistent overlastgevende jongeren in Engeland en Nederland[END_REF][START_REF] Van Swaaningen | Sweeping the street: civil society and community safety in Rotterdam[END_REF].

In this article the Dutch retreat from 'condoning' ASB is examined by identifying the underlying principles offered by politicians for tackling this kind of behaviour. These Dutch rationales are compared to the British ones.

First stage of the empirical study consists of a content analysis of British and Dutch key government and parliamentary documents (debates, votes, reports). 5 In order to produce a brief narrative of the process of policymaking, the focus will be on the development of the Anti-social Behaviour Order (henceforth ASBO). The ASBO as a case study is an easy choice because of its political attraction. Dutch politicians often cite this English measure and refer to the ASBO as a recipe for success [START_REF] Huisman | Administrative measures in crime control[END_REF]. It will be interesting to find out why the ASBO is so appealing for Dutch politicians.

The second stage consists of a series of interviews with key participants in the policy process. 6 The actors involved are Dutch elected officials, Dutch spokesman of political parties and British and Dutch civil servants. The Dutch political landscape is quite diverse. In total eleven different political parties are represented in parliament. Interviews were conducted with the nine biggest. Furthermore four members of city councils of Amsterdam and Rotterdam and five high ranking policymakers were interviewed. 7 The interviews resulted in rich first hand-accounts of the Dutch policy process and of the perceptions of key actors. 8 Why is this kind of elite comparative ethnography useful for the study of policymaking in the sphere of criminal justice?

Policy in the making

There are different macro views on the international component of the origins of crime policies. Some scholars stress the differences in policy interventions between countries [START_REF] Melossi | The cultural embeddedness of social control: reflections on the comparison of Italian and North-American cultures concerning punishment[END_REF][START_REF] Tonry | Symbol, substance and severity in western penal policies[END_REF]. A strong theme within this body of work is the focus upon the socalled American distinctiveness in the area of crime control [START_REF] Jones | Policy transfer and criminal justice. Exploring US influence over British crime control policy[END_REF]. One of the limitations of this approach is that some highly important globalising effects in policy making are overlooked.

On the other hand, there is a substantial body of academic work that stresses the similarities of criminal justice policies [START_REF] Ericson | Crime in an insecure world[END_REF][START_REF] Edwards | Comparing the governance of safety in Europe: a geo-historical approach[END_REF][START_REF] Furedi | Politics of fear. Beyond left and right[END_REF][START_REF] Garland | The culture of control: Crime and social order in contemporary society[END_REF][START_REF] Hudson | Justice in the risk society: challenging and re-affirming justice in late modernity[END_REF][START_REF] Pieterman | De voorzorg cultuur: Streven naar veiligheid in een wereld vol risico en onzekerheid[END_REF]. These academic works argue that the spread of democratic institutions and parallel social and economic forces have shaped related public policies. They highlight the emergence of a common risk society or a culture of control. To illustrate, Garland [START_REF] Garland | The culture of control: Crime and social order in contemporary society[END_REF] argues that crime policies in the UK and USA have become increasingly similar.

Indeed there is much in the Western cultures of control that appears to be in common. But again there are limitations to these studies. 9 In general there is a tendency to overemphasize the trends that confirm this thesis and to downplay divergent developments.

The point of this article is not to deny a general trend of a culture of control or to suggest that differences between countries do not exist. This study does not focus on identifying macro developments. It aims at providing an additional perspective by means of exploring the process of policymaking on a meso-level. 10Policy represents the outcome of a complex set of processes. It is acknowledged that copying or (consciously) overlooking polices from abroad is part of this. But the significance of individual decisions and actions of political actors in this process is often underrated. That is why in this article their views will be studied.

The concept of policy transfer can be useful in this study because it concerns individual political decisions. Policy transfer is defined as a process by which knowledge of policies, administrative measures, institutions and ideas in one political system, are consciously used in the development of policies, administrative measures, institutions and ideas in another political system [START_REF] Dolowitz | A policy-makers guide to policymaking[END_REF].

It is interesting to see whether policy transfer between the UK and the Netherlands has taken place or not. Thereby establishing a difference between soft transfer (including ideas, concepts, lessons and attitudes) and hard transfer (including actual policy instruments and legislation) [START_REF] Evans | Policy transfer in global perspective[END_REF].

Of course with this approach there are limitations as well. For example over emphasizing the degree of individual rationality in policymaking process. The respondents can be rationalising their choices after they were made, but during the process of policymaking they perhaps were less conscious of them.

Furthermore it is difficult to separate external influences from domestic policy developments and external examples can simply serve to confirm an already decided approach. Pollit [START_REF] Pollit | Convergence: the useful myth?[END_REF] points out that labels are frequently borrowed (because of their legitimating power) but in actual action, policy can differ. And there is a tendency of exaggerated claims, assumed from similarities in policy rhetoric. Therefore it is important to look for evidence of non-transfer as well.

English measures and rationales in short

In 1998 the ASBO was introduced in England and Wales. 11 The then Prime minister, Tony Blair, stated that if traditional criminal law processes in cases of antisocial behaviour continued to abide, the rights of victims would be allowed to be routinely trampled upon and would leave courts fighting 21st century crime with 20th century methods. He claimed that the use of control orders was the best available means for protecting the public from ASB. 12 ASBOs have a minimum duration of two years, can last indefinitely, and contain prohibitions considered necessary to prevent the repetition of a person's anti-social behaviour [START_REF] Brown | Anti-social behaviour, crime control and social control[END_REF]. In the law, the conduct is defined as 'behaviour which caused or was likely to cause alarm, harassment, or distress to one or more persons not of the same household as him or herself' [START_REF]A guide to anti-social behaviour tools and powers[END_REF].

In most cases an acceptable behaviour contract (ABC) is issued first. It's a written agreement made between a person who has been involved in ASB and their local authority/landlord or police. ABCs are not legally binding and there does not have to be an ABC in place before an ASBO application is made [START_REF]A guide to anti-social behaviour tools and powers[END_REF]. Then when the agreement is breached in most cases it can be followed up with an ASBO [START_REF] Burney | Making people behave. Anti-social behaviour, politics and policy[END_REF].

The ASBO is a civil order. Restraints of certain behaviour are imposed by a civil court and breaching is a criminal offence [START_REF] Ashworth | Social control and 'anti-social behaviour': the subversion of human rights?[END_REF]. It is a multi step prohibition, a civil order backed up by a criminal penalty [START_REF] Crawford | Dispersal powers and the symbolic role of anti-social behaviour legislation[END_REF]. 13 As Millie [START_REF] Millie | Anti-social behaviour, behavioural expectations and an urban aesthetic[END_REF] pointed out, within a relatively short period of time, the ASBO became in regular usage and is now part of the common lexicon.

In the UK, the government is clear on the question why ASB should be tackled; "Anti-social behaviour ruins lives: It does not just make life unpleasant; it prevents the renewal of disadvantaged areas and creates an environment where more serious crime can take hold," as can be read in several governmental documents [START_REF]Defining and measuring anti-social behaviour[END_REF].

So much is said in one sentence. Jacobson [START_REF] Jacobson | ASBO nation. The criminalisation of nuisance[END_REF] spotted three answers in this single sentence. They argued that this alone may suggest that there is 'room to take a critical view of the different rationales for tackling ASB'. 14 Their study combined empirical research with a review of policy and research literature. They identified among others, the following rationales; -Quality of life; ASB should be tackled because it is a serious problem that makes people miserable and fearful. -Broken windows rationale; ASB should be tackled because if left unattended, it leads to serious crime. 11 The crime and disorder act (1998) introduced ASBOs. 12 <http://www.pm.gov.uk/output/Page11769.asp>. 13 The two-step prohibition structure can be placed in the tradition of the Statutory Nuisance Abatement Notice. It dates back into the 19th Century and would have been a familiar power to the local housing managers who invented the original proposal for the Community Safety Order [START_REF] Ramsay | Vulnerability, sovereignty and police power: A theory of the ASBO[END_REF]. 14 Page 37

-Regeneration rationale; action on ASB should contribute to the social and economic regeneration of local areas.

These British findings formed the starting point of this study. By comparing the English rationales with the underlying reasons of Dutch politicians it will become clear whether policy transfer has taken place or not.

Dutch measures

Recently, as was described in the introduction, Dutch authorities have stepped up their focus of attention for the problem of ASB. Nuisance in the public domain is coupled with war rhetoric and addressed with strong measures. But not so long ago the Dutch were famous for crime policies with a strong 'social'-character [START_REF] Punch | Paradigm lost: the Dutch dilemma[END_REF]. This was combined with the earlier mentioned Dutch practice of condoning (gedogen) also defined as regulated tolerance [START_REF] Brants | Criminologie en politiek[END_REF][START_REF] Buruma | Dutch tolerance: On drugs, prostitution, and euthanasia[END_REF].

But this history of tolerance was one of the first in 21st century Europe to collide with the on-street realities of young Muslim immigrants [START_REF] Vinocur | On Dutch left, a retreat from tolerance of old[END_REF]. In particular around the rise of the populist politician Pim Fortuyn in 2001 there was an increasingly critical public reaction towards this idea of regulated tolerance especially towards young Muslims [START_REF] Pakes | De Britse aanpak van antisociaal gedrag[END_REF]. The general view was that gedogen had gone too far and that authority has lost authority [START_REF] Punch | From 'anything goes' to 'zero tolerance[END_REF].

The Dutch government reacted with the publication of the paper To a safer society [START_REF] Ministerie Van Bzk | Naar een veiliger samenleving[END_REF]. This document appears as also Pakes [START_REF] Pakes | De Britse aanpak van antisociaal gedrag[END_REF] argues, to be the formal beginning of the tougher approach on ASB. It was for the first time that ASB was directly linked to crime and feelings of unsafety. In brief, the government aimed at more police on the street, tougher enforcement of existing rules and where necessary introducing new measures [START_REF] Ministerie Van Bzk | Naar een veiliger samenleving[END_REF].

Later on in October 2004, the Dutch Government was further pressurized to address the problems in the public domain. This heat developed due to a widely publicised case in which a couple had been 'forced out' of their house by harassment from a group of Moroccan youths [START_REF] Koemans | Ten strijde tegen overlast[END_REF]. In short, the couple no longer felt safe in the Diamantbuurt in Amsterdam because they were tormented and called all sorts of names by these youngsters [START_REF] Van Stokkom | Regulering van antisociaal gedrag. Aanpak van persistent overlastgevende jongeren in Engeland en Nederland[END_REF][START_REF] Van Swaaningen | Sweeping the street: civil society and community safety in Rotterdam[END_REF]. The group had ended up throwing stones through the couple's window, and the two moved out of the area. In a reaction several politicians called for tougher measures to tackle 'street terror'. 15 The Minister for Justice considered adopting the ASBO, but after counter-advise from the chief prosecutor the Minister decided against it [START_REF] Burney | Making people behave. Anti-social behaviour, politics and policy[END_REF]. In stead the later discussed ABC-pilot in Rotterdam was introduced.

In 2007 after more incidents of ASB by young Moroccans, 16 discussions in the Dutch parliament of addressing ASB were rekindled. In June of that year, two chairpersons representing local boroughs in Amsterdam 17 suggested introducing the ASBO in the Netherlands. They stated that in the UK it was successful in reducing ASB in inner-city areas. "The ASBO helps in the fight against young people terrorising the streets, before criminal law comes into the picture," said local council chairman Arco Verburg. 18 He referred to the new British laws 'as the best way to respond to problems in the public domain'. 19 In the last three years, there have been several pilots in Rotterdam, Utrecht and Amsterdam copying the ideas of the ASBO. For example the ABC-project in Rotterdam called, 'knock off 20 '. This pilot was based, just like the ASBO, on a multi step approach. The first is an intervention in the form of a contract, issued by a welfare officer or street warden (stadsmarinier) and signed on a voluntary basis by the problem maker. When the contract is breached, an order is issued by the mayor. As soon as this order is violated the culprit will be brought before a criminal court. This is in line with the already existing article 184 Sr (penal code) that prescribes ignoring an official order constitutes a criminal offence and may lead to a penal sanction. During one case in the pilot, a police court judge issued a fine, because a youngster breached a restraining order. 21 The ASBO was a direct inspiration for this pilot, as can be read in the evaluation report. 22 Some high ranking policymakers traveled to the UK and visited the Home Office to get information on the ASBO.

In addition to this pilot, the Dutch government is preparing to enact new administrative legislation that provides local authorities with more legal instruments (often called administrative sanctions) to react to and prevent ASB [START_REF] Lippens | The end of the social: ASBOs in England and Wales[END_REF]. For instance there is a new law in the making; titled severe anti-social behaviour that in many ways is similar to the ASBO. 23 The proposed law 24 gives more power to local authorities. Mayors can issue restraining orders to people who have displayed antisocial behaviour without the interference of a judge and for a longer period of time than the current law allows.

This new law is designed so that the mayor can act quickly when he considers the ASB to be a serious problem. A precise definition of ASB is not given in the proposal, but it declares that the behaviour should be 'persistent and grave'. Information on the case can come from partners in the judicial system, like the police, but also from administrative authorities, like social services and the local Department of Education. The restraining order can be issued for a year and must be revised every 3 months. 25 If the order is breached, it becomes a criminal act (on the basis of the already existing article 184 Sr) and the case can be brought before a criminal court. 26 Although the ASBOs are measures under civil law (with a local judge issuing the order) and the Dutch proposal is based within administrative law (mayor can issue order), the ideas behind it are very similar. Like the English counterpart this 18 <http://www.nicis.nl/nicis/dossiers/Zorgenwelzijn/Jeugdzorg/verrijktdossier/Jongerenoverlast_1132. html> (accessed May 30, 2008). 19 As stated in the Volkskrant (June 13, 2007). 20 Translated as "ff kappe". 21 The evaluation rapport concluded that the effects of the Pilot could not be measured (Letter to parliament Evaluatie Doe-Normaal pilot, Ministerie van Justitie and Minister van BZK, (5554663/08)). 22 See notes in the Letter to parliament Evaluatie Doe-Normaal pilot, Ministry of Justice and the Home Office (5554663/08). 23 Others are, the 'minor nuisance at municipal level act' (still in draft), and 'the public prosecution service settlement act' [START_REF] Devroe | The policy approach of nuisance problems in public space in Belgium and the Netherlands[END_REF]. 24 Official title in Dutch; 'Maatregelen bestrijding voetbalvandalisme en ernstige overlast (31 467).' 25 Or one can be ordered to report at certain times. 26 A prison sentence up to three months or a fine can be the end result.

proposed Dutch law is a multi-stage approach, containing of two different elements (contract and order). Furthermore, breaches of the orders constitute a criminal offence and may lead to penal sanctions (including prison sentences).

In the Netherlands, mayors have more power in this respect than their British counterparts. According to current law, they can also issue restraining orders, but with the new law they can prolong this period and couple it to 'a duty to report'. In addition, the public prosecutor has more authority as well. 27So one can conclude by the measures taken that the English approach appears enormously attractive for Dutch politicians. Although this is not entirely a one-way traffic. In Britain the earlier discussed Dutch-style street wardens were copied [START_REF] Burney | Making people behave. Anti-social behaviour, politics and policy[END_REF]. But still the attraction is for the most part one-sided. Especially the ASBO is seductive. This is remarkable because British scholars regularly criticise the ASBO [START_REF] Garret | Making 'anti-social behaviour': a fragment of the evolution of 'ASBO politics' in Britain[END_REF][START_REF] Von Hirsch | Incivilities: Regulating offensive behaviour[END_REF]. For instance, it has been condemned for potentially criminalising more dayto-day behaviour (the so called net-widening effect) [START_REF] Ashworth | Social control and 'anti-social behaviour': the subversion of human rights?[END_REF][START_REF] Brown | Anti-social behaviour, crime control and social control[END_REF][START_REF] Cobb | Governance through publicity: anti-social behaviour orders, young people and the problematization of the right to anonymity[END_REF][START_REF] Donoghue | Anti-social behaviour orders (ASBOs) in Britain. Contextualizing risk and reflexive modernization[END_REF][START_REF] Hudson | Justice in the risk society: challenging and re-affirming justice in late modernity[END_REF]. Furthermore because it has become a so-called badge of honour. Some teenagers are proud of their cool ASBOs [START_REF] Matthews | Assessing the use and impact of anti-social behaviour orders[END_REF].

Tonry [START_REF] Tonry | Thinking about crime[END_REF] also criticised the ASBO sharply; 'by making ASB into a major social policy problem, and giving it sustained high visibility attention, Labour has made a small problem larger' ( [START_REF] Tonry | Thinking about crime[END_REF]:57).

Also outside the academic world, there is criticism [START_REF] Macdonald | The nature of the Anti-social behaviour order-R (McCann and others) v Crown Court at Manchester[END_REF]. For instance the European commissioner for Human rights expressed his great concern. 28 In Great Brittan ASBOs can be imposed on children as young as ten. The European commissioner feared young children can be detained for breaching ASBOs and can incur a criminal record without actually having committed any recognisable offence [START_REF] Bakalis | ASBOs, preventative orders and the European court of human rights European rights[END_REF][START_REF] Crawford | Dispersal powers and the symbolic role of anti-social behaviour legislation[END_REF].

Another point of interest is the sharp decline in the use of ASBOs in England and Wales in 2006 [START_REF] Burney | Making people behave. Anti-social behaviour[END_REF]. There appears to be a growing disillusion, on a political and practitioners level, with the measure.

It will be interesting to figure out why these negative effects of the ASBO, academic criticism and recent developments appear not to be relevant for Dutch politicians and what the rationales are for the retreat from regulated tolerance.

Dutch political rationales

To get a picture of the underlying reasons for tackling ASB, members of parliament (MPs) and members of the city councils of Amsterdam and Rotterdam 29 were interviewed. They were questioned on the basis of a topic list. 30 Addressing issues like the definition of ASB, the enforcement of current and new measures and reasons for tackling ASB. Subsequent to analysing the results, five rationalities for addressing the problem of ASB have been identified.

the assumed link between disorder and crime

The often cited idea by the respondents is that ASB should be tackled because left unattended it leads to crime. Many respondents state that if minor incidents of ASB are left untouched, disorder can provoke fear, and fear in itself helps to create the physical and social environment in which real crime can develop. 'When people observe that ASB is not addressed, people will feel afraid and withdraw from public spaces; "they will not intervene when they observe crime", as one MP stated.'

The idea of a cycle of ASB, fear and crime is often mentioned. The Broken Window Theory is mentioned as the theoretical idea behind this. One of the MPs directly referred to this theory; "The Broken Window Theory has proven that minor nuisances in the public domain should be addressed by the government to prevent things from getting worse".

Other respondents, upon being asked, say they are familiar with this theory but appear unaware that there is only a weak amount of evidence for this effect. They often state 'this idea is very logical'. So the Broken Window Theory has a very intuitive appeal. In general ASB is perceived as a seedbed of a persistent criminal career; "If politicians do not treat ASB seriously this will definitely lead to problems in the future".

Although some MPs state that the current arsenal of measures is enough to address the problems, the ASBO-approach of New Labour is often (85%) mentioned as the best way forward. One MP directly cited Labour's vision; 'tough on crime, tough on the causes of crime'. He claimed that; 'We can learn from Labour's ideas, because they have the same problems but on a larger scale. So if the ASBO works there it will definitely work here.' Four politicians underlined the idea of the ASBO but argued that it should be coupled with existing social policies addressing the roots of the problems.

economic reasons

The general idea among the respondents is that by tackling ASB, the cycles of economic and social decline in a neighbourhood can be reversed. Some MPs suggest that ASB threatens house prices and discourages investment. They argue that social disorganization and the associated lack of informal social control can lead to a spiral of neighbourhood decline. "Social cohesion is declining, that is a cause of the increasing problem of ASB."

It is not surprising that politicians mention this reason for tackling ASB. The economic theme is an important political issue for the current Dutch administration; they want to turn around the so called 'deprived Neighbourhoods' into 'better-to-do' areas. 31 This urban renewal project is known as the 40 districts approach. 32 Over a thousand million Euro is invested to establish this turnaround. 33 31 Translated in Dutch as 'prachtwijken'or 'Vogelaar-wijken'. 32 Objectives of GSB Urban Policy Programs are • To improve objective and perceived security • To improve the quality of the built environment • To improve social cohesion within society as a whole • Bind middle and higher income groups to the cities • Enhance the economic performance of Dutch cities see http://www.nicis.nl/ kenniscentrum/binaries/nicis/bulk/publicaties/2008/10/engelstalige-factsheet-gsb3-en-krachtwijken.pdf. 33 Kamerstukken II 2007-2008, 28 684, nr. 130, te vinden op <www.minbzk.nl//onderwerpen/veiligheid/ veilige-samenleving/nieuws-en/110943/kabinet-en-gemeenten>.

The ideas of collective efficacy and its close relative the concept of social capital are of importance here. "People must feel connected to their neighbourhood. Tackling ASB will help in restoring community feelings," as a respondent explained. The ASBO is mentioned in this context although several respondents explicitly state that new measures for addressing ASB should be coupled with a social approach as well.

The ideas of Robert Putman appear especially alluring for the Christen Democrats; they often emphasize the importance of social cohesion in relation to ASB. One MP cited from Putmans book Bowling alone [START_REF] Putman | Bowling alone[END_REF]; "Social capital can help to mitigate the dangerous effects of socioeconomic disadvantage".

the idea of the quality of life

All respondents state that ASB is a serious problem that makes people miserable and fearful. Regardless of their political background the politicians say that ASB makes people feel unhappy and unsafe. Quotes like 'security is a necessity of life' and 'ASB can make people feel threatened' are mentioned more than once. So ASB has to be addressed because of the unhappiness it causes. "Even small incidents of ASB can spark a general feeling of insecurity. These incidents have signal value," as one respondent reacted.

Although this is generally a popular theme, some MPs question the feelings of unsafety, suggesting that maybe the attention for ASB is increasing and not so much the actual problem itself. And that the complaints of people are only evidence of an increasing intolerance of young people and minorities. This more sceptical idea is not restricted to one political party, but is mentioned by left wing as well as right wing MPs.

ASB is closely linked to the problem of minorities

The politicians generally emphasize that in inner city areas mostly young immigrants from Morocco are responsible for the nuisance in the public domain. It cannot be a big surprise that especially far right wing parties mentioned this problem, claiming that 'young Moroccans make the streets of big cities unliveable'. And that harsh measures like 'sending them back to Morocco' are the best solution.

However these ideas are not restricted to conservative politicians. All political parties link ASB in some way to the problem of minorities. A number of the MPs argue that because of low levels of social integration young Moroccans terrorise the streets. "Addressing their behaviour with strong measures like restraining orders, a curfew, or behavioural contracts could break the cycle of isolation and alienation of young immigrants," as one respondent suggested.

Also the respondent of one of the country's biggest left-wing party stated that politicians had for too long failed to acknowledge the problems of the integration process. "We focused too long only on welfare. Now is the time to introduce effective punishment for trouble-making young people."

Other politicians approached this subject in a more subtle way and raised the issue of enforcing morals. They state that concepts like responsibility, respect and tolerance and shared understanding of what kind of behaviour is and is not acceptable in Dutch society, should be promoted in general.

Among the different parties there is a universal belief that ASB is getting worse by the day. And that this kind of behaviour is starting at a younger age now, even 12-miners. "Above all, young Moroccans are a large part of this younger group. We have to tackle their ASB with for example contracts coupled with orders, at an early age to prevent things from getting worse. They have to be told that this kind of behaviour is not accepted in the Netherlands," as a member of the government party reasoned.

Legitimacy of the government

Broadly cited by politicians is the idea that ignoring the rising problem of ASB would undermine the credibility of the government. One MP described this idea as follows; "ASB must be addressed, otherwise people will ask; 'Why is this kind of behaviour accepted? And if the police do not act, people will'".

Different respondents refer to the ideas of Pim Fortuyn and claim that after his murder people lost their faith in the government. 34 That is why it is believed the government has to act firmly when confronted with problems in society. It is generally accepted among the respondents that ignoring the problem of ASB can eventually lead to vigilantism. So tackling ASB is deemed necessary in order to keep the confidence of the people. Some MPs question the reasoning that Dutch citizens only want hasher measures to address ASB. They are familiar with the results from recent research that once people were asked what there biggest ASB concern was, 35% stated dog dirt. 35 But the MPs still thought that addressing ASB more firmly was a right route to follow. "No harm done when making the streets safer," as one respondent reasoned. "From my own experience I know that stronger measures help," reacted another.

Three politicians were familiar with a recent report on the effects of punishment. It concluded that there was no proof for the assumption that harsher measures will reduce levels of ASB [START_REF] Wittebrood | Sociale veiligheid ontsleuteld: Veronderstelde en werkelijke effecten van veiligheidsbeleid[END_REF]. These MPs stressed the importance of social policy. "The government cannot act on every form of nuisance in the public domain. We must not create the expectations that we will. It is more important that the root problems of the troublemakers, like truancy are addressed."

However in the end almost all respondents said that they still believed it to be true that harsher measures will tackle ABS. "I just know that addressing ASB is necessary and that the government should act firmly. I do not need scientific arguments to back up these facts," as a respondent ended his interview.

Discussing results

To sum up, the interviews confirm the earlier observation that the ASBO is extremely attractive for Dutch politicians. The same reasoning (measures are needed, ASB is increasing), the same ideas (quality of life, broken window, economic reasons) and the same solutions (behavioural contracts) are used in political arguments. In combination with the earlier described exchange of ideas (Dutch policymakers traveled to the UK to get information on the ASBO) and references to the ASBO in policy documents, it can be concluded that undeniably a soft transfer of policy took place.

Also the intention for hard transfer appears apparent. Both the pilot in Rotterdam as well as the new law in the making (severe anti-social behaviour), refer to the example of the ASBO and the supposed success of the English approach. Although a milder version of the ASBO has been adopted (the ABC in the pilot), at least a form of hard policy transfer indeed did take place [START_REF] Burney | Making people behave. Anti-social behaviour, politics and policy[END_REF].

These results appear to confirm the idea of a common culture of control or risk society [START_REF] Ericson | Crime in an insecure world[END_REF][START_REF] Furedi | Politics of fear. Beyond left and right[END_REF][START_REF] Garland | The culture of control: Crime and social order in contemporary society[END_REF][START_REF] Hudson | Justice in the risk society: challenging and re-affirming justice in late modernity[END_REF][START_REF] Pieterman | De voorzorg cultuur: Streven naar veiligheid in een wereld vol risico en onzekerheid[END_REF]. In short, indeed the two countries faced comparable problems that gave rise to similar (partly copied) solutions and politicians argued along the same lines (see rationales 1, 2, 3).

However these analyses can be misleading. As I stated earlier, in comparative research there is tendency of exaggerated claims, assumed from similarities in policy rhetoric. Therefore in order to get a complete picture, it is important to look for evidence of non-transfer as well. In the sense that dissimilarities in the policy rationales can be identified. 36 In contrast with the parallels, the empirical data also illustrate that Dutch society faces its own particular problems (see rationales 4 and 5). These own rationales can elucidate the Dutch retreat from the policy of turning a blind eye. All respondents coupled young Moroccans with the problems of ASB in inner city areas.

In Dutch inner cities there are troubled community relations with youngsters from minority groups. Especially the Moroccan youth groups are believed to behave in an anti-social manner. Ethnographic fieldwork in Amsterdam showed that this often concerns intimidating group behaviour. De Jong 2007 [START_REF] Jong | Kapot moeilijk[END_REF] who followed a group of Moroccan youngsters over several years stresses their harsh street culture. Being part of a so-called 'Moroccan' street culture stresses their identity and their position in society, which is in turn reinforced by media attention and political worries. In the UK ASB is less coupled with the immigration issue. Perhaps this is not so surprising considering the English class society. The social problems in British inner cities are of a different order. On the notorious housing estates unemployment, crime and ASB trouble all sections of the population; British and immigrants alike. As also Lippens [START_REF] Lippens | The end of the social: ASBOs in England and Wales[END_REF] points out, the Dutch problems are not that severe as in the UK. Most Dutch politicians agreed that the British situation in British cities is worse. "But if the ASBO works even there, it certainly will here," as a city councilor argued.

Furthermore this comparative research shows that Dutch politicians stress 'legitimacy of the government' as a reason for tackling ASB. For the UK this appears a less acute problem. This difference is interesting because in their statements the respondents often use the ASBO as a legitimating power. The supposed success 37 of the ASBO operates as a useful myth that can work in the advantage of the politicians [START_REF] Pakes | De Britse aanpak van antisociaal gedrag[END_REF]. The fact that up until now there has been no objective evaluation report on the introduction of the ASBO available does not seem to influence the ideas of the Dutch policymakers. Parliament recently agreed to prolong the pilot in Rotterdam. 38 36 Besides the most apparent that there are two different judicial systems. 37 There is not yet prove of positive effects of the ASBO. Ipsos MORI a research company will publish an evaluation at the beginning of 2009. 38 Vote on motie Anker, 11-11-2008 (Tcm118-175522).

It is often debated that after the 'Pim-Fortuyn' revolt there is tendency among Dutch politicians to swiftly pick up new trends and catchphrases from abroad [START_REF] Pakes | De Britse aanpak van antisociaal gedrag[END_REF][START_REF] Punch | Paradigm lost: the Dutch dilemma[END_REF][START_REF] Van Swaaningen | Sweeping the street: civil society and community safety in Rotterdam[END_REF]. Almost all the interviewees confirmed this idea of following trends in crime control. They feel that in order to keep (or restore) the faith of the people, new actions against crime and ASB are vital. This could be an explanation for the popularity of the ASBO as well. The British measure functions like a sort of policy umbrella that promises something new and effective. It furthermore legitimises the shift in Dutch policies from social to more repressive measures.

The ASBO is interpreted by the respondents the way they see fit. For instance some describe the ASBO as a preventive measure for 'avoiding things getting worse' or for 'the problems of immigration', others see it as a repressive measure for 'teaching them a lesson'. It is remarkable to see that the 'soft' practices of a strong social policy in neighbourhoods is not completely abandoned. The more left-wing politicians attempt to combine the ASBO with more 'social community work', stressing that the ASBO can only work when social agencies work together to address the root problems as well.

Equally striking is that most politicians do not need real evidence for the effectiveness of the ASBO. The myth of its success is enough. An explanation for this line of reasoning can be the idea of precautionary logic. As also [START_REF] Squires | ASBO nation. The criminalisation of nuisance[END_REF] points out, the zero tolerance approach of ASB appears to be inspired by a precautionary principle, 39 where the lack of scientific evidence is not an excuse of inaction. Also [START_REF] Pieterman | De voorzorg cultuur: Streven naar veiligheid in een wereld vol risico en onzekerheid[END_REF] advocates such a view, arguing that the precautionary principle has become a governmental rationality in many Dutch policy processes. It is a perfect way of doing politics because you do not have to prove anything. Just as [START_REF] Squires | ASBO nation. The criminalisation of nuisance[END_REF] argues, the success of the ASBO is not influenced by scientific research but is more an instinctive response. 40The data presented in this article indeed suggest that the ASBO has in essence an emotive appeal for Dutch politicians as well. But does this confirm the idea of the precautionary principle as a dominant governmental rationality? It could be, but is it not equally true that the policy processes were never really backed up by scientific evidence? Tony Blair himself reflected upon the use of scientific research. "You can argue about statistics until the cows come home and there is usually a very great credibility gap between whatever the statistics put out and whatever people actually think is happening, but the real point is not about statistics, it is about what people feel." 41Also the interviewees confirmed the preference for action above thorough scientific research. In general they argued that tackling ASB both embodies a common-sense understanding and an appeal to popular sentiments. And that there was no time left for inaction. "Something has to be done to tackle street-terror," as a MP stated. "And science is often inconclusive, so we cannot wait." Furthermore, the ASBO has simply a practical appeal. Some respondents claimed it basically fits the already existing set of instruments. For example if the proposed behavioural order is breached, it becomes a criminal act on the basis of the already existing article 184 Sr.

So the established policy transfer of the ASBO can be explained by many different factors. Ranking from the need for symbolic communication with the Dutch people after the populist revolt, being a convenient policy umbrella, to economic reasoning and problems with minorities. A common culture of control is just one of them.

Conclusion

This article empirically tested how much proximity in Dutch and UK policies towards ASB can be explained by intentional efforts to follow the UK Model. And after analyzing the results indeed it can be concluded that a form of policy transfer between the UK and the Netherlands occurred. But what does this mean? What is the relevance of the origins of policy ideas? Why should it matter if inspiration is drawn from another jurisdiction?

As concluded earlier, in criminology there is not much focus on the process of policymaking. This lack in policy research on a meso-level does sometimes lead to assumptions on a macro-level that are not empirically founded. For example in our era of globalisation it is often assumed that similar circumstances will almost inevitably lead to similar outcomes, and that similar policies have their roots in similar rationales.

But this article did not only look at the surface of apparent similarities, it also investigated potential for dissimilarities. By identifying elements of non transfer it illustrated that the human agency is an important element in explanations of contemporary crime control trends.

This research showed translation of policies is not so straightforward and that it is embedded in a cultural context. It demonstrated that policy-making is a messy result of intuitive appeal, traveling myths and unintended consequences. This approach of policymaking is also known as the policy of 'muddling through' [START_REF] Colander | From muddling through to the economics of control: View of applied policy from J.N. Keynes to Abba Lerner[END_REF][START_REF] Hogwood | Beyond muddling through-can analysis assist in designing policies that deliver? Appendix 1, modern policy making[END_REF][START_REF] Parsons | From muddling through to Muddling up. Evidence based policy-making and the modernisation of British government[END_REF].

Although politicians often call for evidence-based policies, in this article it becomes clear that research evidence is often not a base for policies. More often assumed positive effects from abroad, assumed feelings of citizens and assumed proven crime theories form the basis of the policy. Policy transfer appears to be more a form of gaining inspiration, rather than real lesson drawing. This makes the policy making process, unpredictable and not evidence based. This article identifies a form of hyper activity of the Dutch government in creating new measures to tackle ASB. The question is, is such a messy policymaking process a bad thing for society?

The research shows that pilots and laws have advanced in such a frenetic pace as to leave too little space for considered reflection. I would like to argue that more time is needed to reflect on the normative and social implications of legal reforms and their effectiveness in regulating behaviour. The evidence from the UK suggests that the ASBO may end up being counterproductive, alienating young people who feel unfairly treated and stigmatised by such measures. A hard policy transfer of the ASBO can have a boomerang-effect; alienating young Moroccans from Dutch society. This could and should not be the desired result of new Dutch crime policies.

A small city of 70.845 inhabitants (www.gouda.nl)

MP Mark Rutte in the Telegraaf (October

[START_REF] Brants | Criminologie en politiek[END_REF] 2008). M. Koemans (*) University of Leiden, Leiden, the Netherlands e-mail: m.l.koemans@law.leidenuniv.nl

Both 'anti-social behaviour' and 'nuisance in the public domain' are contested concepts. Defining what is currently meant by them is not straightforward and is context-specific. In this article the concepts refer to persistent, un-acceptable non-criminal or minor criminal behaviour of young people in a public order context.

Debate on the 25th of September 2008, after incidents of anti-social behaviour in the city of Gouda lead to widespread public outcry (AD, Telegraaf, NRC).

Key documents are those papers that concern the tackling of ASB after the publication of the Dutch government paper To a safer society[START_REF] Ministerie Van Bzk | Naar een veiliger samenleving[END_REF]. This document has been chosen as a point of departure because as also Pakes[START_REF] Pakes | De Britse aanpak van antisociaal gedrag[END_REF] argues, this appears the formal beginning of the tougher approach on ASB.

The research has been conducted from July till November 2008.

In general I was successful in gaining access to senior politicians and policy-makers. Nonetheless at their request, their quotes have been impersonalized.

In total N=18.

Most writers are aware of the problems of a broad perspective but aimed at understanding macro trends in penal policy[START_REF] Jones | Policy transfer and criminal justice. Exploring US influence over British crime control policy[END_REF].

In this article the meso-level concerns the role of political actors in the policy make-up of their countries crime policies.The war on street 'terror'. Why tackle anti-social behaviour?

0405tkkvr381. Tweede Kamer, vergaderjaar 2004-2005 (vraag 381).

In Amsterdam neighbourhoods (Slovervaart) in Utrecht (Kanaleneiland) and the Hague (Transvaal).

Resp. Slovervaart and de Baarsjes.

For example; Restraining order, duty to report, contact injunction.

Report by Mr Alvaro Gil-Robles, Commissioner for Human Rights, on his visit to the United Kingdom, 4th-12th November 2004, The Office of the Commissioner for Human Rights, Council of Europe, 8 June 2005, pp. 34-37.

The respondents represent various political parties, only when there are notable political differences between the statements is this mentioned.

Topics on the list were; ASB definition, current measures, causes of ASB, reasons for tackling ASB, future, extent of ASB etc.

Thereafter a so-called revolt of the voters.

Veiligheidsmonitor Rijk 2007.

This is based on the precautionary principle used in environmental policies "Where there are threats of serious irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation (United Nations Conference on Environment and Development 1992: principle 15)".

[START_REF] Pollit | Convergence: the useful myth?[END_REF] Earlier Morris[START_REF] Morris | Rethinking risk and the precautionary principle[END_REF] also argued that scientific research is often not the bases for new

policies.[START_REF] Punch | From 'anything goes' to 'zero tolerance[END_REF] Speech at a conference 10 February 2006, available at www.number10.gov.uk (last visited 15 December 2008).

The war on street 'terror'. Why tackle anti-social behaviour?