Does Keck discrimination make any sense? An assessment of the non-discrimination principle within the European Single Market

The aim of this paper is to consider the approach taken by the European Court to discrimination in the post-Keck lines of cases. The previous Article 28 jurisprudence had not considered discrimination in any detail. Thus the Dassonville/Cassis case law had deliberately shunned GATT-style anti-protectionist methods in favor of a more dynamic attack on barriers to trade. However introducing discrimination analysis in Keck has presented problems as the Court has had to work out what kind of methodology to employ. The paper seeks to set out a general framework for understanding discrimination in EC internal market law more broadly. Discrimination involves treating similar situations differently. The framework consists of three types of similar situations that have been employed in the internal market case-law. These are termed market, regulatory and status equivalence. The post-Keck case-law is analyzed in this context. It is concluded that the Court has failed to employ any coherent discrimination methods in to non-product rules. It has failed to set out well-defined product markets where domestic and foreign products compete. It has also failed to establish disparate impact in these markets using convincing methods. Instead it has found ‘discrimination’ based upon judicial hunches or intuitions rather than clear criteria and objective evidence about conditions of competition in the product markets. This has caused litigation to become unpredictable and has left both the European and national courts without any clear criteria for scrutinizing non-product rules. This is reminiscent of the problems that arose in the pre-Keck case-law but now the site of uncertainty is what constitutes ‘discrimination’ rather than what amounts to a barrier to trade. In fact, the case-law exhibits a judicial sleight-of-hand which continues to lean towards the favored ‘barriers to trade’ test under the guise of discrimination analysis. It would be better either to adopt a precise GATT-style economic methodology or to find a coherent European alternative approach. This author favors the latter because the proper concern of EU internal market law since Dassonville has always been the removal of demonstrably arbitrary barriers to trade. Only where a trader can establish that a restriction is truly arbitrary should Article 28 bite. For many non-product rules this will rightly be very difficult to do because such rules pursue broad policy goals that are largely non-justiciable

Ready to Do Whatever it Takes? The Legal Mandate of the European Central Bank and the Economic Crisis

To complement the ‘no shared liability’ rule and public deficit limits, the Maastricht Treaty gave the European Central Bank (ECB) a narrow remit to focus on price stability. Crucially, as a ‘non-sovereign’ central bank, it was unclear that the ECB would act as lender of last resort in the event of market panics. The neoliberal orthodoxy at the heart of Economic and Monetary Union (EMU) held that moral hazard and inflationary risks militated against anything resembling ‘illegal monetary financing’. Following monetary union, markets under-priced risks and encouraged bubbles, but, with the onset of the crisis, sentiment overshot the other way, starving credit from banks and later sovereigns. With bailout funds limited and austerity failing to improve debt spreads, sovereigns became illiquid. ECB officials reluctantly concluded that an uncontrolled sovereign default would threaten the continuation of monetary union. The ECB was thus forced de facto to expand its mandate, first to help banks and, later, to help sovereigns facing loss of access to bond markets. Ultimately this was successful in restoring confidence, but the ECB remained uncomfortable with its role. It has continued to stress its legal limitations and has pressed for reformed governance to enforce fiscal discipline. The economic case for a lender of last resort in a crisis was always strong, but brings with it a worsening moral hazard problem that may invite leaders to avoid the deeper political changes necessary to rebalance the Eurozone

Law and the Financial Crisis: Searching for Europe's New Gold Standard

The role of law in the governance of the Eurozone confronts divergent economic and political perspectives which are reminiscent of the gold standard era. The Maastricht model sought to use to law to create a sound currency. In practice, fixed exchange rates caused large trade imbalances and risky cross-border investments resulting in a Eurozone-wide crisis of first private, and then later, public insolvency. In the face of continued political unwillingness to either pool fiscal resources or impose massive austerity and structural reform, the European Central Bank ECB has been forced to become lender of last resort to sovereigns to maintain the single currency. Ordo-liberal critics argue that the ECB has created a transfer union in breach of the Maastricht agreement. Keynesians, by contrast, argue that, just as under the gold standard, using ‘constitutionalised’ austerity to rebalance trade is neither just nor credible. The Eurozone's reliance on law and markets above developed political institutions has failed, but no democratically legitimate process has replaced it

Cytochrome P450 CYP1 metabolism of hydroxylated flavones and flavonols: Selective bioactivation of luteolin in breast cancer cells.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Natural flavonoids with methoxy substitutions are metabolized by CYP1 enzymes to yield the corresponding demethylated products. The present study aimed to characterize the metabolism and further antiproliferative activity of the hydroxylated flavonoids apigenin, luteolin, scutellarein, kaempferol and quercetin in CYP1 recombinant enzymes and in the CYP1 expressing cell lines MCF7 and MDA–MB–468, respectively. Apigenin was converted to luteolin and scutellarein, whereas kaempferol was metabolized only to quercetin by recombinant CYP1 enzymes. Luteolin metabolism yielded 6 hydroxyluteolin only by recombinant CYP1B1, whereas CYP1A1 and CYP1A2 were not capable of metabolizing this compound. Molecular modeling demonstrated that CYP1B1 favored the A ring orientation of apigenin and luteolin to the heme group compared with CYP1A1. The IC50 of the compounds luteolin, scutellarein and 6 hydroxyluteolin was significantly lower in MDA–MB–468, MCF7 and MCF10A cells compared with that of apigenin. Similarly, the IC50 of quercetin in MDA–MB–468 cells was significantly lower compared with that of kaempferol. The most potent compound was luteolin in MDA–MB–468 cells (IC50= 2±0.3 μM). In the presence of the CYP1-inhibitors α-napthoflavone and/or acacetin, luteolin activation was lessened. Taken collectively, the data demonstrate that the metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. In addition, this antiproliferative activity is attributed to the combined action of the parent compound and the corresponding CYP1 metabolites

Installation of a pilot experimental trench at the Little Forest legacy site

During 2017, a pilot experimental trench was constructed at the Little Forest Legacy Site (LFLS). The objective of installing this trench was to facilitate experimental field-work aimed at further characterising the site, in particular the hydrology of the excavated trenches and of the near-surface layers in which the trenches are located. The test trench is of similar depth to the waste disposal trenches at the legacy site (3 metres) and extends 6 m in length. However, unlike the disposal trenches, the experimental trench contains no waste materials of any kind. Instead, the trench contains a number of sampling points and other instrumentation, and is back filled with river gravel to provide a uniform composition and maintain structural stability. It is intended that the pilot trench will be followed by other trenches with specific experimental objectives. The purposes of this report are to discuss the background, rationale for, and implementation of the facility; to provide a detailed description of the pilot trench; and to compile information and photographs documenting the excavation process. Although some preliminary hydrological data and comparisons with the legacy trenches are presented, the scientific data will be fully discussed and interpreted in future scientific reports

The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkAbstract: Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objectives: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Results: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and -naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusions: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved

Service planning and delivery outcomes of home adaptations for ageing in the UK

In response to the impact of demographic change on the healthcare system, ‘ageing in place’ was introduced as a national policy to support elderly people living independently in their homes. Housing adaptation is essential for successful independent living and has been given increased political priority. However, adaptation policies and practice vary regionally, reflecting statutory limits, policy choices and local planning. This study investigated the current status of adaptation provision in different regions in the UK and assessed the effectiveness of local service planning and management. A mixed-methods sequential explanatory research strategy was employed. In the first quantitative phase, a questionnaire survey was carried out involving all 378 local authorities in England, Scotland and Wales. This was followed by a second qualitative phase involving individual interviews with five professionals and two clients and a focus group meeting with six key stakeholders. The study found that the current number of adaptations was relatively small compared with potential demands in most local areas, as was funding for adaptations. On the operational side, the adaptation process was fragmented, involving different service groups in many local authorities. There were disconnections between these groups, which often caused inefficiencies and poor effectiveness. Moving forward, local authorities need to have a clear vision of the overall need for adaptations and allocate sufficient resources. Practical guidelines are also needed for better integrated working and performance management