Comprehensive validation of published immunohistochemical prognostic biomarkers of prostate cancer-what has gone wrong? A blueprint for the way forward in biomarker studies

BACKGROUND Treatment planning of localised prostate cancer remains challenging. Besides conventional parameters, a wealth of prognostic biomarkers has been proposed so far. None of which, however, have successfully been implemented in a routine setting so far. The aim of our study was to systematically verify a set of published prognostic markers for prostate cancer. METHODS Following an in-depth PubMed search, 28 markers were selected that have been proposed as multivariate prognostic markers for primary prostate cancer. Their prognostic validity was examined in a radical prostatectomy cohort of 238 patients with a median follow-up of 60 months and biochemical progression as endpoint of the analysis. Immunohistochemical evaluation was performed using previously published cut-off values, but allowing for optimisation if necessary. Univariate and multivariate Cox regression were used to determine the prognostic value of biomarkers included in this study. RESULTS Despite the application of various cut-offs in the analysis, only four (14%) markers were verified as independently prognostic (AKT1, stromal AR, EZH2, and PSMA) for PSA relapse following radical prostatectomy. CONCLUSIONS Apparently, many immunohistochemistry-based studies on prognostic markers seem to be over-optimistic. Codes of best practice, such as the REMARK guidelines, may facilitate the performance of conclusive and transparent future studies.

Glue Technology: A Blueprint for Cultural Integration

Despite the gargantuan stakes that mergers and acquisitions represent, global companies' success rate at integrating organizations has been dismal, incurring billions of dollars in lost shareholder value. International human resources' handling of the cultural integration process is the principal differentiator between success and failure. This Capstone project proposes a process for developing cultural integration mechanisms, known as glue technology, and provides a step-by-step process map for execution through four phases. During planning, the need for glue technology is defined. Through analysis, rewards systems are assessed, and a strategy is chosen. In implementation planning, unanimous executive commitment must be secured. Last is measurement based on the integration plan's objectives. Enabling mechanisms such as removing negative influencers, speed, and communication are discussed.

Cambridge Main St. Subway, walls and well found in 1910 while excavating for Harvard Sq. station, blueprint, 1912

Contains blueprint from the Boston Elevated Railway's construction of subway lines underneath Harvard Square. Indicates area of Harvard Yard where construction crews discovered stones likely from the foundation of Goffe College.

EU-IMF assistance to euro area countries: an early assessment. Bruegel Blueprint [No. 19?], 16 May 2013

Three years ago, in May 2010, Greece became the first euro-area country to receive financial assistance from the European Union and the International Monetary Fund in exchange for implementing an economic programme designed by the Troika of the European Commission, the European Central Bank and the IMF. Within a year, Ireland and Portugal went down the same path. This study provides an early evaluation of these assistance programmes implemented by the Troika in these three countries. The study assesses the economic impact of the programmes and the consequences of their particular institutional set-up.

Electricity without borders: a plan to make the internal market work. Bruegel Blueprint Series 20, 5 September 2013

The most straightforward European single energy market design would entail a European system operator regulated by a single European regulator. This would ensure the predictable development of rules for the entire EU, significantly reducing regulatory uncertainty for electricity sector investments. But such a first-best market design is unlikely to be politically realistic in the European context for three reasons. First, the necessary changes compared to the current situation are substantial and would produce significant redistributive effects. Second, a European solution would deprive member states of the ability to manage their energy systems nationally. And third, a single European solution might fall short of being well-tailored to consumers’ preferences, which differ substantially across the EU. To nevertheless reap significant benefits from an integrated European electricity market, we propose the following blueprint: First, we suggest adding a European system-management layer to complement national operation centres and help them to better exchange information about the status of the system, expected changes and planned modifications. The ultimate aim should be to transfer the day-to-day responsibility for the safe and economic operation of the system to the European control centre. To further increase efficiency, electricity prices should be allowed to differ between all network points between and within countries. This would enable throughput of electricity through national and international lines to be safely increased without any major investments in infrastructure. Second, to ensure the consistency of national network plans and to ensure that they contribute to providing the infrastructure for a functioning single market, the role of the European ten year network development plan (TYNDP) needs to be upgraded by obliging national regulators to only approve projects planned at European level unless they can prove that deviations are beneficial. This boosted role of the TYNDP would need to be underpinned by resolving the issues of conflicting interests and information asymmetry. Therefore, the network planning process should be opened to all affected stakeholders (generators, network owners and operators, consumers, residents and others) and enable the European Agency for the Cooperation of Energy Regulators (ACER) to act as a welfare-maximising referee. An ultimate political decision by the European Parliament on the entire plan will open a negotiation process around selecting alternatives and agreeing compensation. This ensures that all stakeholders have an interest in guaranteeing a certain degree of balance of interest in the earlier stages. In fact, transparent planning, early stakeholder involvement and democratic legitimisation are well suited for minimising as much as possible local opposition to new lines. Third, sharing the cost of network investments in Europe is a critical issue. One reason is that so far even the most sophisticated models have been unable to identify the individual long-term net benefit in an uncertain environment. A workable compromise to finance new network investments would consist of three components: (i) all easily attributable cost should be levied on the responsible party; (ii) all network users that sit at nodes that are expected to receive more imports through a line extension should be obliged to pay a share of the line extension cost through their network charges; (iii) the rest of the cost is socialised to all consumers. Such a cost-distribution scheme will involve some intra-European redistribution from the well-developed countries (infrastructure-wise) to those that are catching up. However, such a scheme would perform this redistribution in a much more efficient way than the Connecting Europe Facility’s ad-hoc disbursements to politically chosen projects, because it would provide the infrastructure that is really needed.

Japan and the European Union in the global economy. Bruegel Blueprint 22, 9 April 2014

This book is the final output of a strategic European Union-Japan research partnership, which we initiated in order to deepen our understanding of two major economies facing similar challenges and opportunities. This publication brings together scholars from Kobe University and Bruegel along with selected outside contributors from Japan and the EU from government and leading policy institutions.

Manufacturing Europe's Future. Bruegel Blueprint 21, 2 October 2013

‘Industrial policy is back!’ This is the message given in the European Commission’s October 2012 communication on industrial policy (COM (2012) 582 final), which seeks to reverse the declining role of the manufacturing industry, and increase its share of European Union GDP from about 16 percent currently to above 20 percent. Historical evidence suggests that the goal is unlikely to be achieved. Manufacturing’s share of GDP has decreased around the world over the last 30 years. Paradoxically, this relative decline has been a reflection of manufacturing’s strength. Higher productivity growth in manufacturing than in the economy overall resulted in relative decline. A strategy to reverse this trend and move to an industrial share of above 20 percent might therefore risk undermining the original strength of industry – higher productivity growth. This Blueprint therefore takes a different approach. It starts by looking in depth into the manufacturing sector and how it is developing. It emphasises the extent to which European industry has become integrated with other parts of the economy, in particular with the increasingly specialised services sector, and how both sectors depend on each other. It convincingly argues that industrial activity is increasingly spread through global value chains. As a result, employment in the sector has increasingly become highly skilled, while those parts of production for which high skill levels are not needed have been shifted to regions with lower labour costs.

Towards a new constitutional blueprint for Bosnia and Herzegovina. CEPS Commentary, 20 June 2014

Bosnia-Herzegovina's provisional constitutional system, as created by the Dayton Agreement, has outlived its purpose by more than ten years. Economic and political governance are now even more deadlocked by corruption, political recriminations and institutional failure. Fouéré and Blockmans argue the need for more robust engagement by both the EU and the US and for a constitutional convention to spur reform. This should facilitate the transition from the country’s current status as international protectorate to sustainable self-government, guided by the EU pre-accession process.

Mapping competitiveness with European data. Bruegel Blueprint 23, 6 March 2015

Europe needs improved competitiveness to escape the current economic malaise, so it might seem surprising that there is no common European definition of competitiveness, and no consensus on how to consistently measure it. To help address this situation, this Blueprint provides an inventory and an assessment of the data related to the measurement of competitiveness in Europe. It is intended as a handbook for researchers interested in measuring competiveness, and for policymakers interested in new and better measures of competitiveness. MAPCOMPETE has been designed to provide an assessment of data opportunities and requirements for the comparative analysis of competitiveness in European countries at the macro and the micro level.

Measuring competitiveness in Europe: resource allocation, granularity and trade. Bruegel Blueprint Series Volume XVIV, January 2016

One of the most important lessons learned during the 2008-09 financial crisis was that the informational toolbox on which policymakers base their decisions about competitiveness became outdated in terms of both data sources and data analysis. The toolbox is particularly outdated when it comes to tapping the potential of micro data for the analysis of competitiveness – a serious problem given that it is firms, rather than countries that compete on global markets.

SCANS blueprint for action : building community coalitions.

Shipping list no.: 92-0695-P.

Blueprint reading for the machine trades /

Includes index.

The Human resources management blueprint /

Mode of access: Internet.

Learning a living : a blueprint for high performance : a SCANS report for America 2000.

"April 1992."