Dimethyl N-Aryl phosphoramidates : structural effects on bonding and solvolytic reactivity

Bibliography: p. 84-86.The acid catalysed hydrolysis of a number of ring alkyl substituted dimethyl N-aryl phosphoramidates, (MeO)2P(0)NHAr, has been studied by measuring the rates of hyd~olysis with the aid of a UV spectrophotometer. These rates have been correlated with the pKa values of the corresponding ani I inium iOhs and the slope of this reactivitybasicity relationship for phosphoramidate with ortho substituents (6 = 0~85) is found to differ from that for substrates with meta and para substituents (S = 0,36). Determination of the thermodynamic parameters indicates that the entropy of activation is approximately constant for the substrates studied and the strongly negative values ~ -I -I (~S = 155,4 - 17,5 J mole K ) are consistent with an A2 type mechanism

Brachytherapy for rectal cancer

This thesis describes the use of high-dose-rate endorectal brachytherapy as a boost to external beam radiotherapy in patients with rectal cancer. With 60% clinical complete response in the HERBERT study, this treatment is very promising for use in organ preservation studies. Both toxicity of external beam radiotherapy as toxicity of brachytherapy are addressed and further improvements to the brachytherapy technique are suggested to increase tumor control while limiting toxicity. The work presented in this thesis was financially supported by the Dutch Cancer Society/Alpe d’HuZes Fund (grant number UL2013-6311) and Leiden University Fund (LUF)/Nypels-van der Zee Fonds (grant 3217/28-3-13/NZ). Nucletron/Elekta contributed to the applicators used in the HERBERT study. Cook Medical fiducials were provided without cost for use in the REMARK study.LUMC / Geneeskund

Диалог культур – парадигма современного социокультурного процесса

To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60. μM. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180. μM. For ETH, all endpoints showed similar sensitivity (6.6. mM), whereas MA was the most sensitive parameter for LEV (40. mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET

Environmental factors associated with biological use and surgery in inflammatory bowel disease

Background and Aim: While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. Methods: Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. Results: No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P < 0.05. Two factors were associated with course of CD and ulcerative colitis (UC): beer (CD OR0.3/UC OR0.3) and cannabis (0.5/2.2). While in CD, carpet flooring (0.5) was associated with biological use, and four factors were associated with surgery: working shifts (1.8), appendectomy (2.4), frequent tooth brushing (2.8), and large household size (0.1). For UC, migrants more often required biologicals (10.2). Childhood underweight (3.4), amphetamine use (6.2), and cocaine use (4.8) were associated with surgery. Five factors were replicated. Conclusions: We identified 16 environmental factors nominally associated with biological use and surgery in established IBD. These new insights form an important stepping stone to guide research on biological pathways involved, risk stratification, tailor-made interventions, and preventive strategies in IBD

Predictive factors for response and toxicity after brachytherapy for rectal cancer; results from the HERBERT study

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Brachytherapy for locally advanced cervical cancer: A survey of UK provision of care and support

Background and purpose: Gynaecological brachytherapy can cause anxiety, distress and discomfort. It is not known how variation in delivery impacts women's experiences. To inform future research an online survey was carried out to identify variations in brachytherapy and support available to women receiving treatment for locally advanced cervical cancer (LACC). Materials and methods: An online survey was sent to 44 UK brachytherapy centres using the Qualtrics® survey platform. It included questions about brachytherapy scheduling, inpatient/day case treatment, anaesthetic/analgesia, non-pharmacological support and health professionals’ opinions regarding holistic care. A mixture of closed questions with pre-specified options and open questions were employed. Descriptive statistics were generated to identify variance in UK practice. Free text responses were analysed using inductive content analysis. Results: Responses were received from 39/43 eligible centres (91% response rate). Brachytherapy was predominantly given on an inpatient basis at 65% and day case at 35% of centres. Eleven scheduling regimes were reported with typical duration of brachytherapy ranging from three to 52 h. The main categories identified in response to what worked well were: ‘consistency of staff’; ‘good information provision’ and ‘experienced/skilled/senior staff’. The main categories identified as needing improvement were: ‘training of different staff groups’ and ‘follow up and support’ with many suggestions for service improvements. Conclusion: The survey provided a comprehensive overview of brachytherapy services for LACC demonstrating wide variability in scheduling regimes, duration of treatment and holistic care. The findings support the need to explore women's experiences with a range of treatment regimes and anaesthesia and analgesia techniques to inform improvements to future clinical care