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This article assesses the reasons for frequent national-level administrative reforms in New Zealand and reflects on their potential consequences. It explores three potential reasons: the particularities of Wellington as a highly conducive place for ideas to be shared between decision makers and academics; the characteristics of New Zealand institutions; and the effects of innovations themselves as drivers of disappointment and more innovation. The article reflects on reforms as drivers of continuous and incremental improvements as opposed to a hyper-innovative, politically driven administrative system. It concludes by stressing the importance of incorporating experiences 'from the bottom' in reform processes, and reliance on reflective mechanisms capable of creating opportunities for incremental, piecemeal and often 'inelegant' administrative adjustments. [ABSTRACT FROM AUTHOR]

Backgorund: Quantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy.Aim: We compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm.Methods: 13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares.Results: All HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95).Conclusions: Anatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients. [ABSTRACT FROM AUTHOR]

Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [68Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([68Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [68Ga] DOTATATE, we aimed to quantitatively investigate the biodistribution of [68Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden.Procedures: Of the 44 included patients, 36/44 (82 %) patients demonstrated suspicious radiotracer uptake on [68Ga] DOTATOC positron emission tomography (PET)/X-ray computed tomography (CT). Volumes of interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUVmean) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUVmean, maximum standardized uptake value (SUVmax), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman's rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden.Results: The median SUVmean was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUVmean 6.9, SUVmax 35.5, TBM 42.6 g, and TBU 1.2 %. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUVmean increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUVmean nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3 %) vs. higher TBU (>7 %), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET.Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [68Ga] DOTATOC PET/CT. Potential implications include increased normal organ dose with [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide and decreased absolute lesion detection with [68Ga] DOTATOC in high NET burden. [ABSTRACT FROM AUTHOR]

The result and aftermath of the referendum on the UK's membership of the European Union has generated considerable attention, not just among observers of British politics. Even if some of wider context that shaped the referendum is far from unique to the UK, the road to Brexit is a product of distinct pathologies of the British state and politics that will introduce its own distinctive ways of doing policy and politics: With a state already under strain, a politics that is increasingly divided, and its people(s) discontented, the challenges confronting Britain's ways of governing are substantial. This essay considers three analytical lenses, or 'mega-trends', through which to view the decision of the Cameron government to call the referendum: (1) the electoral politics perspective that focuses on the populist-nationalist turn and fragmentation of the British party system, (2) the dominant policy paradigm perspective that points to a silent crisis of the neoliberal policy consensus that had governed Britain since the 1970s, and (3) the referendum as a side-effect of both depoliticisation and the politics of the regulatory state. Based on these perspectives, we reflect on the potential implications of Brexit for the future of the British state and liberal democracy. [ABSTRACT FROM AUTHOR]

Purpose: In this article, we discuss dynamic whole-body (DWB) positron emission tomography (PET) as an imaging tool with significant clinical potential, in relation to conventional standard uptake value (SUV) imaging. Background: DWB PET involves dynamic data acquisition over an extended axial range, capturing tracer kinetic information that is not available with conventional static acquisition protocols. The method can be performed within reasonable clinical imaging times, and enables generation of multiple types of PET images with complementary information in a single imaging session. Importantly, DWB PET can be used to produce multi-parametric images of (i) Patlak slope (influx rate) and (ii) intercept (referred to sometimes as "distribution volume"), while also providing (iii) a conventional 'SUV-equivalent' image for certain protocols. Results: We provide an overview of ongoing efforts (primarily focused on FDG PET) and discuss potential clinically relevant applications.Conclusion: Overall, the framework of DWB imaging [applicable to both PET/CT(computed tomography) and PET/MRI (magnetic resonance imaging)] generates quantitative measures that may add significant value to conventional SUV image-derived measures, with limited pitfalls as we also discuss in this work. [ABSTRACT FROM AUTHOR]

PET reveals spatially heterogeneous rifampin brain penetration, which decreases rapidly with treatment during tuberculous meningitis. TB on the brain: Children and immunodeficient individuals are especially prone to tuberculosis infections in the brain, causing tuberculous meningitis. Tucker et al. used a rabbit model of tuberculous meningitis and PET imaging to better understand drug distribution. They found that despite sufficient drug concentration in the plasma, rifampin was not penetrating the TB lesions in the brain. These findings were reflected in the imaging of a human patient with tuberculous meningitis. Pharmacokinetic modeling revealed that dosing in pediatric patients would likely need to be adjusted to allow for sufficient rifampin penetration into affected brain areas. Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Current methods to measure intralesional drug distribution rely on tissue resection, which is difficult in humans and generally limited to a single time point even in animals. In this study, we developed a multidrug treatment model in rabbits with experimentally induced TBM and performed serial noninvasive dynamic 11C-rifampin positron emission tomography (PET) over 6 weeks. Area under the curve brain/plasma ratios were calculated using PET and correlated with postmortem mass spectrometry. We demonstrate that rifampin penetration into infected brain lesions is limited, spatially heterogeneous, and decreases rapidly as early as 2 weeks into treatment. Moreover, rifampin concentrations in the cerebrospinal fluid did not correlate well with those in the brain lesions. First-in-human 11C-rifampin PET performed in a patient with TBM confirmed these findings. PK modeling predicted that rifampin doses (≥30 mg/kg) were required to achieve adequate intralesional concentrations in young children with TBM. These data demonstrate the proof of concept of PET as a clinically translatable tool to noninvasively measure intralesional antimicrobial distribution in infected tissues. [ABSTRACT FROM AUTHOR]

An analytical and a comparative perspective are taken to analyze the notion of regulatory failure in the railway domain. The contribution by literature on regulatory failure to the understanding of British and German railway regulation is discussed.

Von der Bonner zur Berliner Republik - 10 Jahre Deutsche Einheit. Edited by ROLAND CZADA and HELLMUT WOLLMANN. Opladen: Westdeutscher Verlag, 2000. Pp.738. DM 98 (paper) ISBN 3-531-13440-X. Since unification [...]

Comparative Public Policy -- Patterns of Post-war Transformation. By FRANCIS G. CASTLES. Cheltenham: Edward Elgar, 1998. Pp.368, [pound]59.95 (cloth) ISBN 1- 858989-816-0; [pound]19.95 (paper) ISBN 1-858989-823-3. The fate of the [...]

The 'Europeanisation' of domestic public policies has been among the key themes in recent reforms in EU member states. This article employs the analytical concept of 'isomorphism' to come to [...]

Purpose: Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for 18F-DCFPyL in nine patients with metastatic prostate cancer.Methods: Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8.7 ± 0.2 mCi) of18F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes.Results: The highest calculated mean AD per unit administered activity of 18F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of 18F-DCFPyL was 0.017 ± 0.002 mSv/MBq.Conclusions: 18F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models. [ABSTRACT FROM AUTHOR]

Societal security poses fundamental challenges for the doctrines of accountability and transparency in government. At least some of the national security state’s effectiveness requires a degree of non-transparency, raising questions about legitimacy. This article explores in cross-national and cross-sectoral perspective, how organizations seek to manage their reputation by accounting for their activities. This article contributes in three main ways. First, it highlights how distinct tasks facilitate and constrain certain reputation management strategies. Second, it suggests that these reputational considerations shape the way in which organizations can give account. Third, it considers three domains associated with societal security, namely intelligence, flood defense, and food safety, in five European countries with different state traditions—the United Kingdom, Germany, Denmark, Sweden, and Norway. By using a “web census,” this article investigates cross-sectoral and cross-national variation in the way organizations seek to account for their activities and manage their reputation. This article finds variation across tasks to be more dominant than national variation. [ABSTRACT FROM AUTHOR]

Purpose In longitudinal oncological and brain PET/ CT studies, it is important to understand the repeatability of quantitative PET metrics in order to assess change in tracer uptake. The present studies were performed in order to assess precision as function of PET/ CT system, reconstruction protocol, analysis method, scan duration (or image noise), and repositioning in the field of view. Methods Multiple (repeated) scans have been performed using a NEMA image quality ( IQ) phantom and a 3D Hoffman brain phantom filled with 18F solutions on two systems. Studies were performed with and without randomly (< 2 cm) repositioning the phantom and all scans (12 replicates for IQ phantom and 10 replicates for Hoffman brain phantom) were performed at equal count statistics. For the NEMA IQ phantom, we studied the recovery coefficients ( RC) of the maximum ( SUVmax), peak ( SUVpeak), and mean ( SUVmean) uptake in each sphere as a function of experimental conditions (noise level, reconstruction settings, and phantom repositioning). For the 3D Hoffman phantom, the mean activity concentration was determined within several volumes of interest and activity recovery and its precision was studied as function of experimental conditions. Results The impact of phantom repositioning on RC precision was mainly seen on the Philips Ingenuity PET/ CT, especially in the case of smaller spheres (< 17 mm diameter, P < 0.05). This effect was much smaller for the Siemens Biograph system. When exploring SUVmax, SUVpeak, or SUVmean of the spheres in the NEMA IQ phantom, it was observed that precision depended on phantom repositioning, reconstruction algorithm, and scan duration, with SUVmax being most and SUVpeak least sensitive to phantom repositioning. For the brain phantom, regional averaged SUVs were only minimally affected by phantom repositioning (< 2 cm). Conclusion The precision of quantitative PET metrics depends on the combination of reconstruction protocol, data analysis methods and scan duration (scan statistics). Moreover, precision was also affected by phantom repositioning but its impact depended on the data analysis method in combination with the reconstructed voxel size (tissue fraction effect). This study suggests that for oncological PET studies the use of SUVpeak may be preferred over SUVmax because SUVpeak is less sensitive to patient repositioning/tumor sampling. [ABSTRACT FROM AUTHOR]