Prenatal screening for congenital heart defects:-the results of the standard anomaly scan in the Netherlands-

Groot, C.J.M. de [Promotor]Blom, N.A. [Promotor]Bax, C.J. [Copromotor]Haak, M.C. [Copromotor

Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case‒control study

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case‒control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case‒control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2–40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma-derived FVIII concentrates (adjusted odds ratio 0·96, 95% confidence interval (CI) 0·36–2·52) or for specific types of FVIII concentrates

Enforcing Security and Safety with Proof-Carrying Code

AbstractIn an environment where more and more code cannot be trusted to behave safety it is becoming necessary to employ mechanisms for detecting and preventing unsafe program behavior. This paper first reviews various such mechanisms and then focuses on static mechanisms with an emphasis on Proof-Carrying Code and its expressiveness.Proof-Carrying Code is a technique that allows a code receiver to verify statically that the code has certain required properties, which are stated in the form of a safety policy. To make this possible the code is accompanied by a representation of an easily checkable formal proof of compliance with the safety policy. This paper discusses first the general properties of the Proof-Carrying Code technique and then explores a particular implementation of the idea using verification condition generators. As a surprising result we prove that by adopting such an implementation choice we limit ourselves to safety properties, which constitute but a subset (albeit a very important one) of all the interesting program properties. We further speculate on what it takes to extend Proof-Carrying Code to handle more that safety properties

Treatment-related risk factors for inhibitor development in non-severe hemophilia A after 50 cumulative exposure days: a case-control study

Background Non-severe hemophilia A patients have a life-long inhibitor risk. Yet, no studies have analyzed risk factors for inhibitor development after 50 factor VIII (FVIII) exposure days (EDs). Objectives This case-control study investigated treatment-related risk factors for inhibitor development in non-severe hemophilia A and assessed whether these risk factors were different for early versus late inhibitor development. Patients/Methods Non-severe hemophilia A patients (FVIII:C 2%-40%) were selected from the INSIGHT study. Inhibitor-positive patients were defined as early (50EDs) cases and matched to 1-4 inhibitor-negative controls by year of birth, cumulative number of EDs, and center/country. We investigated treatment intensity during the last 10 EDs prior to inhibitor development. Intensive treatment was defined as: surgery, peak treatment (10 consecutive EDs), and high mean FVIII dose (>45 IU/kg/ED). Odds ratios (OR) were calculated by logistic regression. Results Of 2709 patients, we analyzed 63 early and 26 late cases and 195 and 71 respectively matched controls. Peak treatment was associated with early and late inhibitor risk (crude OR 1.8, 95% confidence interval [CI] 1.0-3.4; 4.0, 95%CI 1.1-14.3). This association was slightly less pronounced after adjustment for mean FVIII dose. High mean FVIII dose was also associated with early and late inhibitor risk (crude OR 2.8, 95%CI 1.5-5.1; 4.5, 95%CI 1.2-16.6). Surgery increased inhibitor risk for early cases. This was less pronounced for late cases. Conclusions Our findings suggest that intensive FVIII treatment remains a risk factor for inhibitor development in non-severe hemophilia A after more than 50 EDs. Therefore, persistent caution is required throughout the life-time treatment course.Clinical epidemiolog

Menus for Feeding Black Holes

Black holes are the ultimate prisons of the Universe, regions of spacetime where the enormous gravity prohibits matter or even light to escape to infinity. Yet, matter falling toward the black holes may shine spectacularly, generating the strongest source of radiation. These sources provide us with astrophysical laboratories of extreme physical conditions that cannot be realized on Earth. This chapter offers a review of the basic menus for feeding matter onto black holes and discusses their observational implications.Comment: 27 pages. Accepted for publication in Space Science Reviews. Also to appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher

Dissecting intensive treatment as risk factor for inhibitor development in haemophilia

Clinical epidemiolog

Systematic review and meta-analysis of the performance of second-trimester screening for prenatal detection of congenital heart defects

Research into fetal development and medicin

Re: Prenatal detection of congenital heart disease-results of a national screening programme Reply

Research into fetal development and medicin

Head growth in fetuses with isolated congenital heart defects: lack of influence of aortic arch flow and ascending aorta oxygen saturation

Research into fetal development and medicin