De gemeente als eerste overheid in kruiend ijs

In this issue of Bestuurskunde we deal with the claim that municipalities should be first port of call for citizens when it comes to the provision of public services. We discuss what this position means for municipalities and which challenges and dangers it brings

Receptor conversion in distant breast cancer metastases

Introduction: When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor (receptor conversion), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ER alpha), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections. Methods: A total of 233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ER alpha, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result. Results: Using a 10% threshold, receptor conversion by IHC for ER alpha, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from ER+ or PR+ to ER-/PR- and in 3.4% from ER-/PR- to ER+ or PR+ was found. Using a 1% threshold, ER alpha and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from ER+ or PR+ to ER-/PR-, and 8.2% from ER-/PR-to ER+ or PR+ occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ER alpha and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases. Conclusions: Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ER alpha and HER2, and is more frequent for PR, especially in brain, liver and gastrointestinal metastase

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

A Cape of Asia : Essays on European History

A Cape of Asia collects eighteen of Wesseling’s finest essays on European History, clustered around three concerns: The Wider View, or the historical European perspective on globalization, migration and decolonization; Europe’s Identity, reflecting the shift from Eurocentrism to Americanization and Europe’s acceptance of Japan, China and India as new key players in the global economy; and European Ideas about Education, Science, and Art. The third section includes the articles ‘Johan Huizinga and the Spirit of the Nineteen Thirties’ and ‘The Expansion of Europe and the Development of Science and Technology’. A small cape of Asia was how Paul Valéry described Europe in 1919 – a pointed summary of the new mood that came over Europe in the interbellum years. Wesseling’s essays hold to the original sense of the word: personal reflections on vast subjects written for an intellectual and interested but not necessarily specialized readership.9789400600461 (eisbn

A Cape of Asia: Essays on European History

A Cape of Asia collects eighteen of Wesseling’s finest essays on European History, clustered around three concerns: The Wider View, or the historical European perspective on globalization, migration and decolonization; Europe’s Identity, reflecting the shift from Eurocentrism to Americanization and Europe’s acceptance of Japan, China and India as new key players in the global economy; and European Ideas about Education, Science, and Art. The third section includes the articles ‘Johan Huizinga and the Spirit of the Nineteen Thirties’ and ‘The Expansion of Europe and the Development of Science and Technology’. A small cape of Asia was how Paul Valéry described Europe in 1919 – a pointed summary of the new mood that came over Europe in the interbellum years. Wesseling’s essays hold to the original sense of the word: personal reflections on vast subjects written for an intellectual and interested but not necessarily specialized readership

Primitive art, early art or no art at all?

On 20 June 2006 a new museum in Paris opened its doors for the first time, the Mus e du Quai Branly. President Jacques Chirac inaugurated the museum in front of an audience that included, among others, UN Secretary General Kofi Annan and France s most famous anthropologist Claude L vi-Strauss. The museum is another enrichment of that fabulous city, already so well endowed with museums and monuments.The Fifth Republic, founded by General de Gaulle in 1958, has been extraordinarily successful in the creation of new museums. De Gaulle himself did not feel the need to have a special museum built in order to commemorate him. He may have thought that he would be remembered anyway, and he was right. But he certainly stimulated French culture and had Paris embellished in many respects. His famous Minister of Culture Andr Malraux not only ordered the cleaning up of the blackened fa ades of many Paris monuments and other buildings, but also actively stimulated cultural activities outside Paris or, as the French say, in the provinces. Malraux also took a great interest in non-Western art and in this way helped the founding of the Quai Branly museum. De Gaulle s successor, Georges Pompidou, was of course the source of inspiration for the Museum of Modern Art, also known as the Centre Pompidou and particularly famous for its revolutionary architecture. Another less extravagant but also rightly famous building is the Institut du Monde Arabe which dates from the late 1980s and was built by Jean Nouvel, the architect who also built the Quai Branly Museum.