Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting

Regarding: ‘Explorative study to identify novel candidate genes related to oxaliplatin efficacy and toxicity using a DNA repair array'

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Precurved non-tunnelled catheters for haemodialysis are comparable in terms of infections and malfunction as compared to tunnelled catheters: A retrospective cohort study

Background: The main limitations of central venous catheters for haemodialysis access are infections and catheter malfunction. Our objective was to assess whether precurved non-tunnelled central venous catheters are comparable to tunnelled central venous catheters in terms of infection and catheter malfunction and to assess whether precurved non-tunnelled catheters are superior to straight catheters. Materials and methods: In this retrospective, observational cohort study, adult patients in whom a central venous catheter for haemodialysis was inserted between 2012 and 2016 were included. The primary endpoint was a combined endpoint consisting of the first occurrence of either an infection or catheter malfunction. The secondary endpoint was a combined endpoint of the removal of the central venous catheter due to either an infection or a catheter malfunction. Using multivariable analysis, cause-specific hazard ratios for endpoints were calculated for tunnelled catheter versus precurved non-tunnelled catheter, tunnelled catheter versus non-tunnelled catheter, and precurved versus straight nontunnelled catheter. Results: A total of 1603 patients were included. No difference in reaching the primary endpoint was seen between tunnelled catheters, compared to precurved non-tunnelled catheters (hazard ratio, 0.91; 95% confidence interval, 0.70– 1.19, p=0.48). Tunnelled catheters were removed less often, compared to precurved non-tunnelled catheters (hazard ratio, 0.65; 9

Explaining variability in ciclosporin exposure in adult kidney transplant recipients

International audienc

Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib

Objectives Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. This explorative study aims to identify possible relationships between single nucleotide polymorphisms in genes coding for drug metabolizing enzymes and transporter proteins and clearance of danusertib, to clarify the interpatient variability in exposure. In addition, this study explores the relationship between target receptor polymorphisms and toxicity of danusertib. Methods For associations with clearance, 48 cancer patients treated in a phase I study were analyzed for ABCB1, ABCG2 and FMO3 polymorphisms. Association analyses between neutropenia and drug target receptors, including KDR, RET, FLT3, FLT4, AURKB and AURKA, were performed in 30 patients treated at recommended phase II dose-levels in three danusertib phase I or phase II trials. Results No relationships between danusertib clearance and drug metabolizing enzymes and transporter protein polymorphisms were found. Only, for the one patient with FMO3 18281AA polymorphism, a significantly higher clearance was noticed, compared to patients carrying at least 1 wild type allele. No effect of target receptor genotypes or haplotypes on neutropenia was observed. Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity, it is unlikely that danusertib is highly susceptible for pharmacogenetic variation. Therefore, no dosing alterations of danusertib are expected in the future, based on the polymorphisms studied. However, the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research, as we could study only a small group of patients

Gender differences in respiratory symptoms in 19-year-old adults born preterm

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Open Space in Cities The costs and benefits of providing open space in cities

Abstract Although many researchers have investigated the value of open space in cities, few of them have compared them to the costs of providing this amenity. In this paper, we use the monocentric model of a city to derive a simple cost-benefit rule for the optimal provision of open space. The rule is essentially the Samuelson-condition for the optimal provision of a public good, with the price of land as the appropriate indicator for its cost. The condition is made operational by computing the willingness to pay for public and private space on the basis of empirical hedonic price functions for three Dutch cities. The conclusions with respect to the optimal provision of open space differ between the three cities. Further investigation reveals that willingness to pay for parks and public gardens increases with income, although not as fast as that for private residential space. Key words: spatial planning, provision of public goods, cost-benefit analysis JEL code: R52, H41, D61 The authors would like to thank Paul Cheshire, Carel Eijgenraam, Martin Koning, Piet Rietveld and Wouter Vermeulen for very useful comments and Jelte Haagsma for research assistance. The authors would also like to thank the Dutch Association of Real Estate Agents (NVM) for using their data. Introduction It is generally recognized that market failures and external effects abound in urban economics (see, for instance, Anas, Arnott and Small, 1998), but it is often not completely clear how effective various possible measures are in improving resource allocation. A specific example is the evaluation of spatial planning policy, which is an almost universally an important part of urban policy. Although economists have paid attention to various aspects of spatial planning (see, for instance, Fischel (1985) on zoning) much remains to be learned. This paper focuses on one aspect of spatial planning within cities: the provision of open space in the form of parks and public gardens. These are generally considered to be important amenities and many studies have confirmed their significance for the well being of urban residents, usually on the basis of hedonic price studies. A glance at the literature suggests that most studies stop after having established that statistically significant benefits are present. However, for a complete cost-benefit analysis we also need to assess the costs of these amenities. In this paper we make an attempt to introduce the cost side into the analysis by deriving a cost-benefit rule that can be made operational by means of hedonic analysis. We apply this result to the provision of open space in three large cities of the Netherlands. In the densely populated Netherlands, spatial planning imposes tight restrictions on land use throughout the country, but especially on the western part, which is the economic centre. Probably the best known feature of Dutch physical planning is the prolonged attempt to preserve the polder landscape in the so-called Green Heart of the country's economic core region, the Randstad. As a consequence, the cities in that part of the country are more compact than they would otherwise probably have been. A framework for cost-benefit analysis In this section, we develop a model for a monocentric city in which a benevolent planner provides open space by means of spatial planning policy. The model is outlined in 2.1 and the policy evaluation question is considered in 2.2. Section 2.3 discusses the suggested cost-benefit rule and its operationalization and applicability in real world circumstances. The model We consider the demand for open space in a monocentric city, which is the workhorse of urban The utility function of the household is: (2.1) and the budget restriction: with y denoting household income, p i the price of land in neighbourhood i, t the commuting cost per unit t of distance, and x i the distance between neighbourhood i and the city centre. We have normalized the price of the composite good to 1. Households maximize their utility by choosing a neighbourhood i and thereby determining their optimal consumption of housing and the composite good. The price for land in the neighbourhoods adjusts in such a way that in every neighbourhood the same level of utility is reached. It is well known that the equilibrium rent level in the city can be described by a bid rent function. A bid rent function gives the maximum amount of money a household is willing to pay for one unit of land when it has to reach utility level u* and income, unit commuting cost and the available amount of open space are given. Formally, the bid rent function ψ is defined for each neighbourhood i as: where ( ) ⋅ C denotes the amount of the composite good that a household must consume in order to reach utility u* conditional on housing consumption h i and open space i S . 2 The first order condition of the maximization in (2.3) implies: This equation states that the value of the bid rent function equals the household's marginal willingness to pay for land. In a market equilibrium all households have the same gross income and reach the same utility level and are therefore on the same bid rent curve. The value of this bid rent curve is then equal to the price of land i p . Optimal provision of open space The amount of land available for residential purposes (R i ) and parks or public gardens (S i ) in neighbourhood i is L i . For simplicity we take this amount to be equal in all neighbourhoods. (At the end of the next section we will relax this assumption.) To study the optimal provision of open space in the city, we introduce a planner who maximizes the value of the social surplus generated by the city. This surplus is defined as the difference between the total amount of income earned in the city and the costs that have to be made to enable its inhabitants to reach a given utility level u*. The social planner chooses h i , R i and S i such that the value of the social surplus of each neighbourhood i (SS i ) is maximized, while taking into account the constraint: The social surplus SS of the city is the sum of the social surpluses of all neighbourhoods: In these equations i µ is the Lagrange multiplier associated with constraint (2.6). We can easily remove it by combining the last two conditions as: We assume that a neighbourhood will be developed whenever it contributes to the total surplus of the city, that is, whenever the value of the land in residential use (the provision of the appropriate amount of open space included) exceeds its value in agricultural use. This is similar to the way the boundary of the city is determined in monocentric models where no neighbourhoods are distinguished. A cost-benefit rule The derivations of the previous subsection suggest a relatively straightforward cost-benefit rule for the provision of open space. Open space should be provided until the sum of the marginal willingness to pay of all the inhabitants of a neighbourhood is equal to the market value of residential land in the neighbourhood: It should, of course, immediately be noted that neither the willingness to pay for open space nor the market value of residential land is directly observable. Open space is a public good for which no market price exists and urban residential land is in practice almost always traded jointly with the houses constructed on it. Fortunately, both problems can be solved by the hedonic method. To see this, observe that in a market equilibrium every household must reach the equilibrium utility level u*. This requires that a hedonic price function ( ) emerges that facilitates such an equilibrium. The budget restriction of a household can then be written as , and we can substitute it in the utility function to write the condition for a market equilibrium as: (2.12) Even though this hedonic price function is only defined in our model for a finite number of neighbourhoods, we may reasonably conjecture that a smooth function exists that takes on the same values as the actual hedonic function for all neighbourhoods and is also defined for other possible combinations of h, S, and x. Since small changes in h, S and x should not change utility, this more general smooth hedonic price function must have: It follows immediately from (2.13) that the partial derivative of the hedonic price function with respect to h is the marginal willingness to pay for residential land, and from (2.14) that the partial derivative of the hedonic price function with respect to S is the marginal willingness to pay for open space. Equation (2.15) shows the familiar property that the house price should contain a compensation for commuting cost. The version of the cost-benefit rule (2.11) that will be used in our empirical work is therefore: Existing literature The value of open space has been studied intensively over the past decades. For instance, an early study by Since a recent survey of the international literature on the valuation of open space is available, we will only briefly discuss a few studies for the Netherlands, to which our empirical work refers. Luttik (2000) studied a limited number of relatively small areas and found that a view on open space increases the value of a house with 6 to 12 percent. However, she reported that it was much more difficult to demonstrate any effect of a park or a recreational area bordering the residential area. For only two of the eight areas she examined significant coefficients for these variables were found. Visser and van Dam (2005) for distances well below the 500 m used in the Dutch white paper mentioned in the introduction