Literatuurscan oorzaken geweld tegen kinderen en jongeren in afhankelijkheidsrelaties

Naar aanleiding van het rapport van de Commissie Seksueel misbruik van minderjarigen in de Rooms-Katholieke Kerk (Commissie Deetman), heeft de Minster van Veiligheid en Justitie, mede namens de Staatssecretaris van VWS, een onderzoek naar dieperliggende oorzaken van seksueel geweld en andere vormen van geweld in afhankelijkheidsrelaties toegezegd aan de Tweede Kamer. Dit onderzoek heeft betrekking op de eerste fase van het onderzoek. Het betreft een literatuurscan die de stand van de wetenschappelijke kennis op hoofdlijnen in kaart moet brengen met betrekking tot de etiologie van seksueel geweld en fysiek geweld tegen kinderen en jongeren, binnen afhankelijkheidsrelaties. De volgende deelvragen staan daarbij centraal: - Wat is de stand van de kennis over de etiologie van fysieke kindermishandeling en seksueel misbruik? - Waar liggen grofweg de mogelijkheden om te interveniëren? - Op welke thema's zou nader, al dan niet empirisch, onderzoek in Nederland wenselijk zijn en hoe zou dat er idealiter uitzien

Disquieting presences: the ambiguity and indeterminacy of Maurice Nio’s architecture

© The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background In recent years, Dutch architect Maurice Nio has built an array of projects in the Netherlands, which have generally been considered within the spectrum of the Superdutch phenomenon, and more broadly, within Iconic Architecture. Seemingly, to his Dutch colleagues, Nio's work is on the track of liberating architecture from the burden of cultural responsibilities (Ibelings Supermodernism: Architecture in the age of globalization: Nai Uitgevers Pub, 1998), yet it evinces significant differences from other work in that vein. Methods Nio’s projects are compared with Jencks' phenomenology of iconic architecture (Jencks The iconic building: Rizzoli New York, 2005), in order to demonstrate the importance and peculiarity of Nio’s work within the context of Iconic Architecture and the Superdutch period, and the extent to which his work can be considered different. Results This article argues that Nio’s architecture is not based on the production of outstanding shapes (Lootsma SuperDutch Afterthoughts Post. Rotterdam. Rotterdam: 010 Publisher, 2001), or the clever interpretation of a given program (Betsky Reading MVRDV: NAi 2003), but on the creation of disquieting presences in the built environment. Most of his work consists of pieces of architecture each of which has its own name, character and identity and seems to rely on disrupting the expected and disturbing the quiet. Conclusions This paper examines Nio’s work, with particular attention to three case studies, in order to generate a series of qualitative characteristics that define his idiosyncratic architecture.Peer reviewedFinal Published versio

Sensitizing thermochemotherapy with a PARP1-inhibitor

Cis-diamminedichloroplatinum(II) (cisplatin, cDDP) is an effective chemotherapeutic agent that induces DNA double strand breaks (DSBs), primarily in replicating cells. Generally, such DSBs can be repaired by the classical or backup non-homologous end joining (c-NHEJ/b-NHEJ) or homologous recombination (HR). Therefore, inhibiting these pathways in cancer cells should enhance the efficiency of cDDP treatments. Indeed, inhibition of HR by hyperthermia (HT) sensitizes cancer cells to cDDP and in the Netherlands this combination is a standard treatment option for recurrent cervical cancer after previous radiotherapy. Additionally, cDDP has been demonstrated to disrupt c-NHEJ, which likely further increases the treatment efficacy. However, if one of these pathways is blocked, DSB repair functions can be sustained by the Poly-(ADP-ribose)-polymerase1 (PARP1)-dependent b-NHEJ. Therefore, disabling b-NHEJ should, in principle, further inhibit the repair of cDDP-induced DNA lesions and enhance the toxicity of thermochemotherapy. To explore this hypothesis, we treated a panel of cancer cell lines with HT, cDDP and a PARP1-i and measured various end-point relevant in cancer treatment. Our results demonstrate that PARP1-i does not considerably increase the efficacy of HT combined with standard, commonly used cDDP concentrations. However, in the presence of a PARP1-i, ten-fold lower concentration of cDDP can be used to induce similar cytotoxic effects. PARP1 inhibition may thus permit a substantial lowering of cDDP concentrations without diminishing treatment efficacy, potentially reducing systemic side effects

Enhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia

Background: Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhibited by hyperthermia, thereby inducing synthetic lethal conditions in every tumor type. Since cisplatin is successfully used combined with hyperthermia (thermochemotherapy), we investigated the effectiveness of combining PARP1-i with thermochemotherapy. Results: The in vitro data demonstrate a decreased in cell survival after addition of PARP1-i to thermochemotherapy, which can be explained by increased DNA damage induction and less DSB repair. These in vitro findings are in line with in vivo model, in which a decreased tumor growth is observed upon addition of PARP1-i. Materials and Methods: Survival of three HR-proficient cell lines after cisplatin, hyperthermia and/or PARP1-i was studied. Cell cycle analyses, quantification of γ-H2AX foci and apoptotic assays were performed to understand these survival data. The effects of treatments were further evaluated by monitoring tumor responses in an in vivo rat model. Conclusions: Our results in HR-proficient cell lines suggest that PARP1-i combined with thermochemotherapy can be a promising clinical approach for all tumors independent of HR status

Literatuurscan oorzaken geweld tegen kinderen en jongeren in afhankelijkheidsrelaties

Violence against children committed by people placed in a position of care and trust is a topic associated with considerable social uproar. This report contains a literature review of the underlying causes of sexual violence and other forms of violence within relationships of dependency. The three main questions are: What is the current knowledge of the aetiology of child physical abuse and child sexual abuse?Are there options for intervention?Which topics require examination and which shape should future research concerning these topics take?Naar aanleiding van het rapport van de Commissie Seksueel misbruik van minderjarigen in de Rooms-Katholieke Kerk (Commissie Deetman), heeft de Minster van Veiligheid en Justitie, mede namens de Staatssecretaris van VWS,  een onderzoek naar dieperliggende oorzaken van seksueel geweld en andere vormen van geweld in afhankelijkheidsrelaties toegezegd aan de Tweede Kamer. Dit onderzoek heeft betrekking op de eerste fase van het onderzoek. Het betreft een literatuurscan die de stand van de wetenschappelijke kennis op hoofdlijnen in kaart moet brengen met betrekking tot de etiologie van seksueel geweld en fysiek geweld tegen kinderen en jongeren, binnen afhankelijkheidsrelaties. De volgende deelvragen staan daarbij centraal: Wat is de stand van de kennis over de etiologie van fysieke kindermishandeling en seksueel misbruik? Waar liggen grofweg de mogelijkheden om te interveniëren? Op welke thema's zou nader, al dan niet empirisch, onderzoek in Nederland wenselijk zijn en hoe zou dat er idealiter uitzien? INHOUD: 1. Inleiding 2. Methode 3. Fysieke mishandeling binnen het gezin 4. Seksueel misbruik binnen het gezin 5. Seksueel misbruik buiten het gezin 6. Conclusie en discussi

De mediatisering van de strafrechtspleging

Criminal Justice: Legitimacy, accountability, and effectivit