The impact of trust on private equity contracts

This paper adresses the impact of trust on private equity contracts. Trust between investor and entrepreneur is essential to help overcome control problems, especially in an environment with severe agency risks and incomplete contracts. In this study, information about the effects of trust is collected using a simulation with 144 entrepreneurs and investors. We find that trust has an impact on the desired contracts of entrepreneurs, but not on that of investors. Our findings suggest that for parties, faced with potentially large agency problems (investors), trust and control seem to play complementary roles. On the other hand, for parties faced with smaller agency problems (entrepreneurs), trust seems to be a substitute for control

De integratie van de IDAA in de handelingsgerichte diagnostiek van dyslexie bij 16+

Om een gefundeerde en wetenschappelijk onderbouwde diagnose van dyslexie te stellen bij jongvolwassenen, is het noodzakelijk om beroep te doen op goed genormeerde testinstrumenten. Het klassieke testinstrumentarium richt zich echter niet primair op de leeftijdscategorie 16+. Bovendien ontbreken vaak geschikte Vlaamse normen (Depessemier & Andries, 2009). Naast een tekort aan wetenschappelijk genormeerde testinstrumenten is er nood aan diagnostiek in een handelingsgericht kader. De handelingsgerichte diagnostiek vertrekt vanuit een totaalprofiel, waarbij de diagnosticus leerproblemen onderkent, analyseert en zoekt naar mogelijke verklaringen. Het begin is de hulpvraag van de cliënt, het eindproduct is een verantwoord en bruikbaar advies dat gericht is op het oplossen van die problemen (Pameijer & van Beukering, 2004). Ook de Stichting Dyslexie Nederland (2008) stuurt aan op het onderzoeken van leerproblemen in hun totaliteit. In het handelingsgericht kader zijn drie vormen van diagnostiek noodzakelijk: de onderkennende, verklarende en indicerende diagnostiek. Het huidige onderzoeksproject, de ontwikkeling en normering van de Interactieve Dyslexietest Amsterdam-Antwerpen (IDAA), komt hieraan tegemoet voor de diagnostiek van dyslexie bij jongvolwassenen. De IDAA, ontwikkeld door de Universiteit van Amsterdam en het Multidisciplinair Diagnostisch Centrum voor Leerstoornissen in samenwerking met Muiswerk Educatief, is een wetenschappelijk en voor Nederland en Vlaanderen genormeerd diagnostisch instrumentarium. Het is een computergestuurde test die zich richt op het basisfenomeen van dyslexie: ernstige lees- en/of spellingproblemen op woordniveau t.o.v. een relatieve normgroep (Van den Broeck, 2002). Het doel van de IDAA is drieledig: 1. Informatie geven over de ernst van lees- en spelproblemen met het oog op het onderkennen van dyslexie; 2. Informatie geven die bijdraagt tot de verklaring van dyslexie; 3. Inzicht geven in relatief sterke en zwakke punten in het beheersingsprofiel en een bijdrage leveren tot de indicerende diagnose van dyslexie. De verschillende subtests meten zowel de geautomatiseerde woordherkenning, het fonologisch decoderen, de orthografische en de fonologische competentie. Dit gebeurt aan de hand van flitstaken waarin woorden (zowel Nederlandse als Engelse) en pseudowoorden voor korte tijd worden aangeboden en zo beroep doen op geautomatiseerde processen. Deze methode vormt een meerwaarde ten aanzien van de klassieke testen omdat in talen met een transparant schrift zoals het Nederlands, dyslexie bij 16+ veeleer wordt gekenmerkt door een gebrek aan snelheid bij het maken van klanktekenkoppelingen (De Jong & van der Leij, 2003; Geudens, 2006). Onderzoek toont aan dat het probleem van dyslectici met de verwerkingssnelheid (‘speed-of-processing’) door flitsaanbieding prominent op de voorgrond komt en dat het probleem zicht het sterkst manifesteert wanneer het geflitste woord onbekend is (Yap & van der Leij, 1993). Reactietijd en accuratesse worden bovendien ook op itemniveau gemeten. Het normeringsonderzoek, uitgevoerd bij 1307 jongeren uit de onderwijstypes ASO, TSO en BSO, toont het belang aan van de vergelijking van de testresultaten met een relatieve normgroep. Eerste analyses tonen aan dat de scores voor leerlingen van het ASO hoger liggen dan deze voor het TSO en BSO. Ook de resultaten van het TSO en BSO verschillen van elkaar, in het voordeel van het TSO. Het instrument toont een goede test-hertestbetrouwbaarheid. De criteriumvaliditeit werd onderzocht bij 81 jongvolwassenen met en 52 jongvolwassenen zonder dyslexie. Binaire logistische regressies tonen aan dat de IDAA-subtests de aanwezigheid van problemen in geautomatiseerde woordherkenning, fonologische decoderen, orthografische competentie en fonologische competentie adequaat voorspellen. Klassieke tests (zoals EMT en Klepel) en IDAA-subtests correleren significant op de vier componenten van het lees- en schrijfproces. De resultaten zullen in de poster verder worden uitgediept. Aan de hand van de IDAA kan een sterkte-zwakte profiel opgesteld worden. Er wordt een analyse gemaakt van de scores op elk van de vier componenten van het lees- en schrijfproces. Binnen de subtests wordt bekeken of er significante verschillen zijn tussen woorden met verschillende woordlengte, tussen bestaande woorden en pseudowoorden en tussen leenwoorden en Nederlandse woorden. Bijkomende factoren zoals cognitieve vaardigheden, compensatiemogelijkheden, het sociaal-emotioneel functioneren en metacognitieve vaardigheden hebben eveneens een invloed op de ervaren problematiek. Deze factoren kunnen aan de hand van observatie, intakegegevens en verder onderzoek in kaart gebracht worden en dienen mee geïntegreerd te worden in de sterkte-zwakte analyse. Zodoende vormt deze analyse een uitgangspunt voor adviezen die betrekking hebben op onderwijs- en examenfaciliteiten, remediëring, compensatiehulpmiddelen en eventueel studiemethode. We kunnen besluiten dat de IDAA een geschikt diagnostisch instrument is dat binnen de handelingsgerichte diagnostiek kan worden aangewend, teneinde vanuit een totaalbeeld handvatten aan te reiken voor begeleiding en ondersteuning van jongvolwassenen met dyslexie.status: publishe

Combined effect of polymorphisms in Rad51 and XRCC3 on breast cancer risk and chromosomal radiosensitivity

Enhanced in vitro chromosomal radiosensitivity (CRS) has been proposed as a marker for low-penetrance gene mutations predisposing to breast cancer (BC). Since the double strand break (DSB) is the most detrimental form of DNA damage induced by ionizing radiation, it is possible that mutations in genes encoding proteins involved in DSB repair affect breast cancer risk. The purpose of the present study was to examine whether five single nucleotide polymorphisms (SNPs) in Rad51 and Xrcc3 (rs1801320, rs1801321, rs1799796, rs861539 and rs1799794) exhibited an association with breast cancer susceptibility in a Belgian population of BC patients with a known or putative genetic predisposition. We also ascertained whether a relationship exists between the occurrence of the 'variant' alleles of these variations and in vitro CRS. Blood samples were obtained from BC patients and from healthy female individuals. Variations in the 5' UTR of Rad51 and Xrcc3 were genotyped, and statistical analysis was performed. The results showed that low-penetrant variations in Rad51 and Xrcc3, two proteins belonging to the homologous recombination DSB repair pathway, may modify BC risk in patients already carrying a pathological mutation in the highly penetrant BC genes BRCA1 and BRCA2. Combined risk genotype analysis revealed that Rad51 SNPs enhance BC risk in BRCA2 patients, whereas Xrcc3 SNPs significantly enhance BC risk in carriers of BRCA1 mutations and in patients with hereditary BC. When four putative risk genotypes of Rad51 and Xrcc3 were combined, positive significant odds ratios were obtained in the entire patient population and in patients with a hereditary history of disease. Although obtained from a limited number of patients, our data are supportive of a polygenic model whereby combinations of weak variations are responsible for an enhanced BC risk by acting jointly with high-penetrant mutations in BRCA1 or BRCA2

Chromosomal radiosensitivity of triple negative breast cancer patients

Purpose: Based on clinical and molecular data, breast cancer is a heterogeneous disease. Breast cancers that have no expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are defined as triple negative breast cancers (TNBCs); luminal cancers have different expressions of ER, PR and/or HER2. TNBCs are frequently linked with advanced disease, poor prognosis and occurrence in young African women, and about 15% of the cases are associated with germline BRCA1/2 mutations. Since radiotherapy is utilized as a principle treatment in the management of TNBC, we aimed to investigate the chromosomal instability and radiosensitivity of lymphocytes in TNBC patients compared to luminal breast cancer patients and healthy controls using the micronucleus (MN) assay. The effect of mutations in breast cancer susceptibility genes on chromosomal radiosensitivity was also evaluated. Methods: Chromosomal radiosensitivity was evaluated in the G0 (83 patients and 90 controls) and S/G2 (34 patients and 17 controls) phase of the cell cycle by exposing blood samples from all patients and controls to 2 and 4 Gy ionizing radiation (IR). Results: In the G0 MN assay, the combined cohort of all breast cancer, TNBC and luminal patients' exhibit significantly elevated spontaneous MN values compared to controls indicating chromosomal instability. Chromosomal radiosensitivity is also significantly elevated in the combined cohort of all breast cancer patients compared to controls. The TNBC patients, however, do not exhibit enhanced chromosomal radiosensitivity. Similarly, in the S/G2 phase, 76% of TNBC patients do not show enhanced chromosomal radiosensitivity compared to the controls. In both the G0 and S/G2 phase, luminal breast cancer patients demonstrate a shift toward chromosomal radiosensitivity compared to TNBC patients and controls. Conclusions: The observations of the MN assay suggest increased chromosomal instability and chromosomal radiosensitivity in South African breast cancer patients. However, in TNBC patients, the irradiated MN values are not elevated. Our results suggest that the healthy lymphocytes in TNBC patients could handle higher doses of IR

Radiosensitivity analysis in patients with a primary immunodeficiency disease

Primary Immune Deficiency Diseases (PIDs) are life-threatening genetic disorders of the immune system. A subset of PIDs is caused by mutations in genes involved in the repair of DNA double-strand breaks, by which affected patients may also be radiosensitive. For many reasons PID patients can be exposed to radiation (bone marrow transplantation, radiotherapy, diagnostic imaging), but this may pose serious risks to radiosensitive subjects. Surprisingly, radiosensitivity testing is currently not included in the workup of PIDs in most European countries. The main goal of our study is to translate radiosensitivity analysis in the diagnostic workup for PIDs in Belgium. To this aim, two cell-cycle specific in vitro radiosensitivity assays will be included in the standard diagnostic procedures in patients with suspected PID at the Ghent University Hospital (reference center for Belgium): (1) the G0 cytokinesis-block micronucleus assay (CBMN) which is about to be translated into the clinical practice, (2) the S/G2 CBMN which has been developed in our labs with positive proof-of-concept but which must be further optimized before translation. Both assays will be performed on peripheral blood lymphocytes of the patients. Furthermore, radiosensitivity assays will also be optimized for fibroblasts, obtained from skin biopsies of patients. In our study design, radiosensitivity analysis will be the central core of two innovative diagnostic and therapeutic algorithms, which will include immunophentyping, direct subsequent genetic analysis and guide optimal patient care. Micronucleus analysis in lymphocytes of patients is currently ongoing and first results will be presented. We believe that inclusion of radiosensitivity testing will represent a major improvement in the timely diagnosis and management of patients affected by these life-threatening, heterogeneous and difficult-to-diagnose diseases

Assessment of radiation sensitivity in patients with a primary immunodeficiency disease

Primary Immune Deficiency Diseases (PIDs) are life-threatening genetic disorders of the immune system. A subset of PIDs is caused by mutations in genes involved in the repair of DNA double-strand breaks, by which affected patients may also be radiosensitive. For many reasons PID patients can be exposed to radiation (bone marrow transplantation, radiotherapy, diagnostic imaging), but this may pose serious risks to radiosensitive subjects. Surprisingly, radiosensitivity testing is currently not included in the workup of PIDs in most European countries. The main goal of our study is to translate radiosensitivity analysis in the diagnostic workup for PIDs in Belgium. To this aim, two cell-cycle specific in vitro radiosensitivity assays will be included in the standard diagnostic procedures in patients with suspected PID at the Ghent University Hospital (reference center for Belgium): (1) the G0 cytokinesis-block micronucleus assay (CBMN) which is about to be translated into the clinical practice, (2) the S/G2 CBMN which has been developed in our labs with positive proof-of-concept but which must be further optimized before translation. Both assays will be performed on peripheral blood lymphocytes of the patients. Furthermore, radiosensitivity assays will also be optimized for fibroblasts, obtained from skin biopsies of patients. In our study design, radiosensitivity analysis will be the central core of two innovative diagnostic and therapeutic algorithms, which will include immunophentyping, direct subsequent genetic analysis and guide optimal patient care. Micronucleus analysis in lymphocytes of patients is currently ongoing and first results will be presented. We believe that inclusion of radiosensitivity testing will represent a major improvement in the timely diagnosis and management of patients affected by these life-threatening, heterogeneous and difficult-to-diagnose diseases

Mild Social Stress in Mice Produces Opioid-Mediated Analgesia in Visceral but Not Somatic Pain States.

Visceral pain has a greater emotional component than somatic pain. To determine if the stress-induced analgesic response is differentially expressed in visceral versus somatic pain states, we studied the effects of a mild social stressor in either acute visceral or somatic pain states in mice. We show that the presence of an unfamiliar conspecific mouse (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared with mice tested alone, suggesting that the mere presence of a stranger is stressful. We then observed noxious visceral or somatic stimulation-induced nociceptive behavior in mice tested alone or in mildly stressful conditions (ie, beside an unfamiliar stranger). Compared with mice tested alone, the presence of a stranger produced a dramatic opioid-dependent reduction in pain behavior associated with visceral but not somatic pain. This social stress-induced reduction of visceral pain behavior relied on visual but not auditory/olfactory cues. These findings suggest that visceral pain states may provoke heightened responsiveness to mild stressors, an effect that could interfere with testing outcomes during simultaneous behavioral testing of multiple rodents. In mice, mild social stress due to the presence of an unfamiliar conspecific mouse reduces pain behavior associated with noxious visceral but not somatic stimulation, suggesting that stress responsiveness may be enhanced in visceral pain versus somatic pain states