In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice.

The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence microscopy and two-dimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from 100 microm to 300 microm. Two morphometric parameters - the percentage of intervascular distances larger than 200 microm (ivd200) and the non-perfused area fraction at a distance larger than 100 microm from a nearest perfused vessel (area100), - were deduced from these experiments and related to the P(i)/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly with the percentage of ivd200 and the area100

Q-Curves with Complex Multiplication

The Hecke character of an abelian variety A/F is an isogeny invariant and the Galois action is such that A is isogenous to its Galois conjugate A^σ if and only if the corresponding Hecke character is fixed by σ. The quadratic twist of A by an extension L/F corresponds to multiplication of the associated Hecke characters. This leads us to investigate the Galois groups of families of quadratic extensions L/F with restricted ramification which are normal over a given subfield k of F. Our most detailed results are given for the case where k is the field of rational numbers and F is a field of definition for an elliptic curve with complex multiplication by K. In this case the groups which occur as Gal(L/K) are closely related to the 4-torsion of the class group of K. We analyze the structure of the local unit groups of quadratic fields to find conditions for the existence of curves with good reduction everywhere. After discussing the question of finding models for curves of a given Hecke character, we use twists by 3-torsion points to give an algorithm for constructing models of curves with known Hecke character and good reduction outside 3. The endomorphism algebra of the Weil restriction of an abelian variety A may be determined from the Grössencharacter of A. We describe the computation of these algebras and give examples in which A has dimension 1 or 2 and its Weil restriction has simple abelian subvarieties of dimension ranging between 2 and 24

Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection

Item does not contain fulltextIn C6 rat brain glioma, we have investigated the relation between hypoxia and the presence of lipid droplets in the cytoplasm of viable cells adjacent to necrosis. For this purpose, rats were stereotaxically implanted with C6 cells. Experiments were carried out by the end of the tumour development. A multifluorescence staining protocol combined with digital image analysis was used to quantitatively study the spatial distribution of hypoxic cells (pimonidazole), blood perfusion (Hoechst 33342), total vascular bed (collagen type IV) and lipid droplets (Red Oil) in single frozen sections. All tumours (n=6) showed necrosis, pimonidazole binding and lipid droplets. Pimonidazole binding occurred at a mean distance of 114 microm from perfused vessels mainly around necrosis. Lipid droplets were principally located in the necrotic tissue. Some smaller droplets were also observed in part of the pimonidazole-binding cells surrounding necrosis. Hence, lipid droplets appeared only in hypoxic cells adjacent to necrosis, at an approximate distance of 181 microm from perfused vessels. In conclusion, our results show that severe hypoxic cells accumulated small lipid droplets. However, a 100% colocalisation of hypoxia and lipid droplets does not exist. Thus, lipid droplets cannot be considered as a surrogate marker of hypoxia, but rather of severe, prenecrotic hypoxia

Breast cancer risk among first-generation migrants in the Netherlands

We investigated breast cancer incidence in migrants in the Netherlands in 1988-1998. The standardised incidence ratio for breast cancer in Northwest-Netherlands was statistically significantly reduced for women born in Surinam (0.56), Turkey (0.29) and Morocco (0.22). The proportion of women with advanced stages (III and IV) did not differ significantly between migrants and women born in the Netherlands

Compositional specification of functionality and timing of manufacturing systems

In this paper, a formal modeling approach is introduced for compositional specification of both functionality and timing of manufacturing systems. Functionality aspects can be considered orthogonally to the timing. The functional aspects are specified using two abstraction levels; high-level activities and lower level actions. Design of a functionally correct controller is possible by looking only at the activity level, abstracting from the different execution orders of actions. Furthermore, the specific timing of actions is not needed. As a result, controller designcan be performed on a much smaller state space compared to an explicit model where timing and actions are present. The performance of the controller can be analyzed and optimizedby taking into account the timing characteristics. Since formal semantics are given in terms of a (max, +) state space, various existing performance analysis techniques can be used. Weillustrate the approach, including performance analysis, on an example manufacturing system

Symptoms of depression are associated with physical inactivity but not modified by gender or the presence of a cardiovascular disease; a cross-sectional study

Background: Depressive symptomatology may act as a barrier to enhance physical activity. This phenomenon is predominantly found in patients with an established cardiovascular disease (CVD) and in female patients. This cross-sectional study investigated (1) the association between symptoms of depression and physical inactivity, and (2) whether this association is different between primary and secondary prevention patients, and between men and women. Methods: The study design concerns a secondary analysis of baseline data from a randomized clinical trial, including primary and secondary prevention patients (n = 2184; mean age 71.6 ± 8.94), from 34 general practitioner panels. The Rapid Assessment of Physical Activity questionnaire (RAPA) was used to measure patient reported activity levels. Symptoms of depression were determined using the Patient Health Questionnaire (PHQ-9). Multilevel linear regression analysis was used to explore the association between symptoms of depression and physical activity while adjusting for confounders. Gender and whether or not having a CVD were considered as potential effect modifiers for the association between symptoms of depression and inactivity. Results: Symptoms of depression were associated with lower levels of physical activity. This association was neither different for men and women nor for primary and secondary prevention patients. Conclusion: In primary care patients’ symptoms of depression were associated with physical inactivity. This association was not modified by gender or the presence of a CVD. Future research should focus on lifestyle interventions aiming at the increase of physical activity levels, while emphasizing on improving symptoms of depression in men, women, and patients both with and without a history of CVD

Motor performance in five-year-old extracorporeal membrane oxygenation survivors: a population-based study

Contains fulltext : 79690.pdf (publisher's version ) (Open Access)INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a cardio-pulmonary bypass technique to provide life support in acute reversible cardio-respiratory failure when conventional management is not successful. Most neonates receiving ECMO suffer from meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), sepsis or persistent pulmonary hypertension (PPH). In five-year-old children who underwent VA-ECMO therapy as neonates, we assessed motor performance related to growth, intelligence and behaviour, and the association with the primary diagnosis. METHODS: In a prospective population-based study (n = 224) 174 five-year-old survivors born between 1993 and 2000 and treated in the two designated ECMO centres in the Netherlands (Radboud University Medical Centre Nijmegen and Sophia Children's Hospital, Erasmus MC - University Medical Center Rotterdam) were invited to undergo follow-up assessment including a paediatric assessment, the movement assessment battery for children (MABC), the revised Amsterdam intelligence test (RAKIT) and the child behaviour checklist (CBCL). RESULTS: Twenty-two percent of the children died before the age of five, 86% (n = 149) of the survivors were assessed. Normal development in all domains was found in 49% of children. Severe disabilities were present in 13%, and another 9% had impaired motor development combined with cognitive and/or behavioural problems. Chi-squared tests showed adverse outcome in MABC scores (P < 0.001) compared with the reference population in children with CDH, sepsis and PPH, but not in children with MAS. Compared with the Dutch population height, body mass index (BMI) and weight for height were lower in the CDH group (P < 0.001). RAKIT and CBCL scores did not differ from the reference population. Total MABC scores, socio-economic status, growth and CBCL scores were not related to each other, but negative motor outcome was related to lower intelligence quotient (IQ) scores (r = 0.48, P < 0.001). CONCLUSIONS: The ECMO population is highly at risk for developmental problems, most prominently in the motor domain. Adverse outcome differs between the primary diagnosis groups. Objective evaluation of long-term developmental problems associated with this highly invasive technology is necessary to determine best evidence-based practice. The ideal follow-up programme requires an interdisciplinary team, the use of normal-referenced tests and an international consensus on timing and actual outcome measurements

Motor performance in five-year-old extracorporeal membrane oxygenation survivors: a population-based study

Contains fulltext : 79690.pdf (publisher's version ) (Open Access)INTRODUCTION: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a cardio-pulmonary bypass technique to provide life support in acute reversible cardio-respiratory failure when conventional management is not successful. Most neonates receiving ECMO suffer from meconium aspiration syndrome (MAS), congenital diaphragmatic hernia (CDH), sepsis or persistent pulmonary hypertension (PPH). In five-year-old children who underwent VA-ECMO therapy as neonates, we assessed motor performance related to growth, intelligence and behaviour, and the association with the primary diagnosis. METHODS: In a prospective population-based study (n = 224) 174 five-year-old survivors born between 1993 and 2000 and treated in the two designated ECMO centres in the Netherlands (Radboud University Medical Centre Nijmegen and Sophia Children's Hospital, Erasmus MC - University Medical Center Rotterdam) were invited to undergo follow-up assessment including a paediatric assessment, the movement assessment battery for children (MABC), the revised Amsterdam intelligence test (RAKIT) and the child behaviour checklist (CBCL). RESULTS: Twenty-two percent of the children died before the age of five, 86% (n = 149) of the survivors were assessed. Normal development in all domains was found in 49% of children. Severe disabilities were present in 13%, and another 9% had impaired motor development combined with cognitive and/or behavioural problems. Chi-squared tests showed adverse outcome in MABC scores (P < 0.001) compared with the reference population in children with CDH, sepsis and PPH, but not in children with MAS. Compared with the Dutch population height, body mass index (BMI) and weight for height were lower in the CDH group (P < 0.001). RAKIT and CBCL scores did not differ from the reference population. Total MABC scores, socio-economic status, growth and CBCL scores were not related to each other, but negative motor outcome was related to lower intelligence quotient (IQ) scores (r = 0.48, P < 0.001). CONCLUSIONS: The ECMO population is highly at risk for developmental problems, most prominently in the motor domain. Adverse outcome differs between the primary diagnosis groups. Objective evaluation of long-term developmental problems associated with this highly invasive technology is necessary to determine best evidence-based practice. The ideal follow-up programme requires an interdisciplinary team, the use of normal-referenced tests and an international consensus on timing and actual outcome measurements