Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Design Issues for General-Purpose Adaptive Hypermedia Systems

A hypermedia application offers its users much freedom to navigate through a large hyperspace. For authors finding a good compromise between offering navigational freedom and offering guidance is difficult, especially in applications that target a broad audience. Adaptive hypermedia (AH) offers (automatically generated) personalized content and navigation support, so the choice between freedom and guidance can be made on an individual basis. Many adaptive hypermedia systems (AHS) are tightly integrated with one specific application. In this paper we study design issues for general-purpose adaptive hypermedia systems, built according to an application-independent architecture. We use the Dexter-based AHAM reference model for adaptive hypermedia [7] to describe the functionality of such systems at the conceptual level. We concentrate on the architecture and behavior of a general-purpose adaptive engine. Such an engine performs adaptation and updates the user model according to a set of adaptation rules specified in an adaptation model. In our study of the behavior of such a system we concentrate on the issues of termination and confluence, which are important to detect potential problems in an adaptive hypermedia application. We draw parallels with static rule analysis in active database systems [1,2]. By using common properties of AHS we are able to obtain more precise (less conservative) results for AHS than for active databases in general, especially for the problem of termination

Modellen voor marketing-insights: uit de beroepspraktijk van consumentengedrag, marktonderzoek en analytics

Modellen voor Marketing-Insights is het eerste overzicht van de belangrijkste modellen voor consumentengedrag, marktonderzoek en digital analytics in Nederland. Dankzij die modellen kunnen we bij complexe marketingvraagstukken snel tot de kern van een probleem komen en slagvaardig advies geven, of gericht onderzoek opzetten voor de ontwikkeling van effectief beleid. Aan de hand van Kotlers planningsproces en op basis van echte vragen uit de marketingpraktijk, kunt u snel doorbladeren naar een specifieke marketingvraag en inzicht krijgen in het model dat antwoord geeft op die vraag en de context waarin het model wordt gebruikt. Zo kunt u een gefundeerde keuze maken, gesteund door praktische tips & tricks voor de toepassing. Meer informatie is te vinden op www.mi-modellen.nl. Door het overzicht, de structuur en samenhang die dit boek biedt, vormt. De auteurs, Anita Cox, Erik de Kort en Norbert Scholl, hebben alledrie jarenlange beroepservaring in de marktonderzoekpraktijk aan bureauzijde en in het HBO-onderwijs. Ze zijn actief binnen de MOA, Expertise Center voor Marketing-Insights, Onderzoek & Analytic

Capacité de liaison du calcium des orthophosphates et polyphosphates organiques et inorganiques.

The aim of this research was to determine the calcium-binding capacity of inorganic and organic ortho- and polyphosphates. This calcium-binding capacity can be used to influence the stability of, for example, casein micelles in dairy systems. Four phosphates were selected: disodium uridine monophosphate (Na$_2$UMP, organic orthophosphate), disodium hydrogen phosphate (Na$_2$HPO$_4$, inorganic orthophosphate), sodium phytate (SP, organic polyphosphate), and sodium hexametaphosphate (SHMP, inorganic polyphosphate). Concentrations of up to 100 mmol$\cdot$L$^{-1}$ phosphate were added to a 50 mmol$\cdot$L$^{-1}$ CaCl$_2$ solution. The samples were prepared at pH 8.0 and were analyzed before and after sterilization for calcium-ion activity, conductivity, pH, sediment, and turbidity. Both SHMP and SP are strong chelators, as calcium ions bind to these phosphates in the ratio of 3:1 and 6:1, respectively. Calcium ions also strongly bind to Na$_2$HPO$_4$, but in a ratio of 3:2 with insoluble Ca$_3$(PO$_4$)$_2$ complexes as result. The equilibrium position of Na$_2$UMP is not strong towards the chelated complex, and significant levels of free calcium and free phosphate can exist. An equilibrium constant of $0.29 \pm 0.08$ L$\cdot$mol$^{-1}$ was determined for calcium uridine monophosphate (CaUMP) complexes. Both calculation of the equilibrium constant and analysis on the CaUMP precipitate confirmed a reactivity of 1:1 between calcium and Na$_2$UMP. The CaUMP complexes are well soluble at ambient temperature, and insoluble complexes appear after sterilization, because the solubility of CaUMP decreases during heating. Finally, we concluded that the structure of phosphate molecules determines their calcium-binding capacity rather than organic or inorganic origin of phosphates.Le but de cette recherche était de déterminer la capacité de liaison du calcium des orthophosphates et polyphosphates inorganiques et organiques. Cette capacité de liaison du calcium peut être utilisée pour influencer la stabilité des micelles de caséine dans les systèmes laitiers. Quatre phosphates ont été sélectionnés : l'uridine monophosphate disodique (Na$_2$UMP, orthophosphate organique), l'hydrogenophosphate disodique (Na$_2$HPO$_4$, orthophosphate inorganique), le phytate de sodium (SP, polyphosphate organique) et l'hexametaphosphate de sodium (SHMP, polyphosphate inorganique). Des concentrations de phosphate allant jusqu'à 100 mmol$\cdot$L$^{-1}$ ont été ajoutées à une solution contenant 50 mmol$\cdot$L$^{-1}$ de calcium. Les échantillons préparés à pH 8,0 ont été analysés avant et après stérilisation pour l'activité de l'ion calcium, la conductivité, le pH, le sédiment et la turbidité. SHMP et SP sont tous les deux des chélateurs forts, puisque les ions calcium sont liés à ces phosphates dans un ratio 3:1 et 6:1 respectivement. Les ions calcium sont aussi fortement liés au Na$_2$HPO$_4$, mais dans un ratio de 3:2, résultant dans la formation de complexes insolubles de Ca$_3$(PO$_4$)$_2$. Le Na$_2$UMP n'est pas aussi fortement complexé et des taux significatifs de calcium libre et de phosphate libre peuvent exister. Une constante d'équilibre de $0,29 \pm 0,08$ L$\cdot$mol$^{-1}$ a été déterminée pour les complexes d'uridine monophosphate de calcium (CaUMP). Le calcul de la constante d'équilibre et l'analyse du précipité deCaUMPont confirmé l'un et l'autre une réactivité de 1:1 entre le calcium et le Na$_2$UMP. Les complexes CaUMP sont bien solubles à température ambiante mais des complexes insolubles apparaissent après stérilisation parce que la solubilité du CaUMP diminue au cours du chauffage. Finalement, nous pouvons conclure que la structure des molécules de phosphate détermine leur aptitude à lier le calcium plus que l'origine organique ou inorganique des phosphates

An alternative ventilation system for operating theatres:an experimental and CFD study on the performance of a local ventilation device

A local operating theatre ventilation device which ventilates the wound area only, was investigated applying a parameter study. The ventilation device is combined with a blanket which lies over the patient during the operation. Two configurations were studied: configuration 1 where HEPA-filtered air was supplied around and parallel to the wound area and configuration 2 where HEPA-filtered air was supplied from the top surface of the blanket, perpendicular to the wound area. The objective of the parameter study was to identify critical parameters. A simplified setup, which consisted of a sideways contaminated airflow and a HEPA-filtered airflow, was studied by experiments and CFD simulations. Particle concentrations (≥0.5µm) were measured at the wound, relative to a non-ventilated situation with only sideways contaminated airflow (N=30 per series; expressed in %). The effect of supply velocity, temperature and contaminant velocity were investigated. In isothermal conditions relative particle concentrations of 0-11% and 0-1% were measured for configuration 1 and 2 with a supply velocity of 0.40m/s and 0.30m/s respectively. However, differences between both configurations were not significant. Furthermore, configuration 1 was more sensitive to lower supply velocities (P&lt;0.04) and higher supply temperatures (P&lt;0.04). CFD simulations showed similar trends, although absolute values were more positive.</p