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Patients with hepatocellular carcinoma (HCC) face a common type of cancer, which is amongst the most deadly types of cancer worldwide. The therapeutic options range from curative resection or ablation to loco regional therapies in palliative setting and last but not least, systemic treatment. The latter group underwent major changes in the last decade and a half. Since the introduction of sorafenib in 2007, many other systemic treatments have been investigated. Most without success. It took more than ten years before lenvatinib could be added as alternative first-line treatment option. Just recently a new form of systemic treatment, immunotherapy, entered the field of therapeutic options in patients with HCC. Immune checkpoint inhibitors are becoming the new standard of care in patients with HCC. Several reviews reported on the latest phase 1/2 studies and discussed the higher response rates and better tolerability when compared to current standard of care therapies. This review will focus on elaborating the working mechanism of these checkpoint inhibitors, give an elaborate update of the therapeutic agents that are currently available or under research, and will give an overview of the latest trials, as well as ongoing and upcoming trials.

Bayesian inference for rank-order problems is frustrated by the absence of an explicit likelihood function. This hurdle can be overcome by assuming a latent normal representation that is consistent with the ordinal information in the data: the observed ranks are conceptualized as an impoverished reflection of an underlying continuous scale, and inference concerns the parameters that govern the latent representation. We apply this generic data-augmentation method to obtain Bayes factors for three popular rank-based tests: the rank sum test, the signed rank test, and Spearman’s ρs.

Contains fulltext : 226717.pdf (Publisher’s version ) (Closed access) Despite an ongoing stream of lamentations, many empirical disciplines still treat the p value as the sole arbiter to separate the scientific wheat from the chaff. The continued reign of the p value is arguably due in part to a perceived lack of workable alternatives. In order to be workable, any alternative methodology must be (1) relevant: it has to address the practitioners' research question, which - for better or for worse- most often concerns the test of a hypothesis, and less often concerns the estimation of a parameter; (2) available: it must have a concrete implementation for practitioners' statistical workhorses such as the t test, regression, and ANOVA; and (3) easy to use: methods that demand practitioners switch to the theoreticians' programming tools will face an uphill struggle for adoption. The above desiderata are fulfilled by Harold Jeffreys's Bayes factor methodology as implemented in the open-source software JASP. We explain Jeffreys's methodology and showcase its practical relevance with two examples. 9 p.

International audience; During the filtration of colloidal dispersions by a membrane, pores often get clogged by the suspended particles. Knowing the shape and size of the particles that cause this clog would be a great help to membrane users since they could then choose the ideal filtering device. Microfluidic technology enables the fabrication of model membranes or filters that are transparent, which allows for measuring the particle geometrical features that deposit either at the surface of the pores or on top of the fouling layer that has already formed. However, the use of microfluidic filters have been confined to the study of clog formation at the pore scale, overlooking the influence of the dynamics of the particle deposition on the clogging process. We have recently shown that looking precisely at what is deposited and how this is captured inside the pore provides new insight into the clogging process. In particular, we have found that a minute concentration of aggregates in a supposedly monodisperse dispersions are mainly responsible for pore fouling. In this paper, we use the same imaging technique to determine the entire clogging process for different types of monodisperses dispersions under various flow conditions, DLVO interactions with the pore walls, and confinements. We show that the way clogs form is appear complex but is also quite systematic in the fact that aggregates are the building blocks of the clog. Pores are clogged by progressive accumulation of aggregates with the average size of the aggregate required to cause the blockage increasing with increasing flow velocity. This work demonstrates that particle size and shape distributions of the feeding dispersion must be determined to understand which physical mechanisms are at play during the clogging process.

A forensic mental health report is requested in about 30% of more serious cases presented to the criminal court. These reports can be used at sentencing and advise the judge on criminal responsibility, recidivism risk, and possible treatment measures, but is not a formal factor in decisions about guilt. The current study focuses on the (unwarranted) effect of forensic mental health information on conviction decisions. Using an experimental vignette study among 155 criminology students, results show that when a mental disorder is present, conviction rates are higher than when such information is absent. In line with the story model of judicial decision-making, additional analyses showed that this effect was mediated by the evaluation of guilt rather than by the evaluation of other physical evidence. Implications for further research and practice are discussed.

Against a background of the pluralisation of policing in contemporary city spaces, and sustained interests in the assessment of policing in the criminology and criminal justice literatures, the current study seeks to draw a comparative analysis in trust between policing actors, as experienced by nightlife consumers. While studies on trust in the police are numerous, this is much less the case for other actors involved in policing urban (nightlife) spaces. Neither is it very well understood how trust is distributed between policing actors. It is important to investigate this, taking into consideration the privatisation and technologisation of safety provision in contemporary cities, and the legitimacy of the actors involved. Using a survey, 894 youths enrolled in education were asked to evaluate their trust in actors involved in the policing of urban nightlife areas: the police, door staff, and CCTV. Results showed that people tend to trust human policing agents more compared to technological agents. A cluster analysis further indicated that alongside this general pattern, four additional groups can be found in the data: two groups that display the highest trust in either the police or door staff with intermediate trust in CCTV, and two groups expressing either overall low trust or overall high trust, independent of the policing actor. Employing logistic regression analyses, we find that demographic, victimisation, and contextual variables predict cluster membership. We end with suggestions for future research and reflect on whether the privatisation and technologisation of (nightlife) policing are desirable from a nightlife consumer point of view.

People are often confronted with injustice that is done to others. In such cases, observers (i.e. third-parties) of injustice can restore justice by punishing the perpetrator, as shown by a vast amount of research. However, this focus on punishment has led to the neglect of another behavioural option: compensation of the victim. The current review focuses on this latter behavioural option. More specifically, it is argued that third-parties are more compensation-oriented than previous literature appears to demonstrate. To support this argument, previous research is discussed and the factors that might explain observers’ preference for compensation are outlined. To conclude, suggestions for future research are presented.

This review covers the research and industrial activities on mainly Ga- and Zn-promoted ZSM-5 catalysts for the production of bio-aromatics in the thermochemical conversion of biomass and waste. The promoted ZSM-5 catalysts currently favoured in biomass aromatization have not initially been designed for biomass processing, but for the conversion of petrochemical feeds. In biomass pyrolysis, however, aromatization catalysts have to perform additional tasks to aromatization, such as cracking, reforming, decarboxylation, decarbonylation and the water-gas shift reaction. In addition, catalysts in biomass processing may have to operate with feeds containing acids, sulphur, nitrogen and minerals. Nevertheless, there is great similarity between the optimum catalysts for both petrochemical and biomass aromatization. The preferred aromatization catalysts for both gasification and pyrolysis are Ga- and Zn-promoted ZSM-5 catalysts that synergistically combine a dehydrogenation and an acidic function. Reduced extra-framework Ga cations residing at ZSM-5 exchange positions in close proximity to Bronsted acid sites are the likely active sites for aromatization. For Ga a reduction/oxidation activation procedure to form these sites is beneficial. For Zn/ZSM-5 catalysts ZnOH+ species appear to be the active sites. For these catalysts no reduction/oxidation activation is required. The key process parameters for aromatization are a temperature of 400–550 °C and a low space velocity of 0.5–1.0 h−1. In agreement with the bifunctional nature of Ga/ZSM-5 there exists an optimal Ga loading for each SAR. Best results were obtained with a molar ratio Ga/H+ or Zn/H+ close to 1.0. These catalysts also show the best stability

Nous abordons ici l’etude de la phenomenologie des objets visuels a partir de comptes rendus verbaux, de reponses a des questions ou de descriptions spontanees, ainsi que d’associations libres. Nous demandons meme parfois aux sujets de realiser de simples croquis. Cet eventail de methodes permet de sonder la structure profonde de la conscience visuelle. Celle-ci est avant tout revelee par ce qui n’est pas spontanement mentionne par des qualites accidentelles ou encore par des changements induits lors de variations ou ajouts mineurs. Nous avons trouve une concordance remarquable parmi un grand nombre de participants. Ceci demonte que les comptes-rendus verbaux permettent d’explorer puissamment la structure de la conscience visuelle. Tout comme le langage, les « objets visuels simples » ont des racines profondes dans la conscience. Ces fondations « invisibles » servent a definir des figures simples, un « carre » par exemple, comme des objets prototypiques et uniques. La nature des « objets visuels » implique ainsi l’existence d’un « vaste domaine invisible ». Sans une telle prise en compte, la comprehension correcte de la nature de l’objet visuel n’est pas possible. Cette decouverte devrait permettre de mener a une theorie de la syntaxe formelle des formes visuelles fondamentales.

We consider techniques used in the articulation of pictorial relief. The related ‘cue’ best known to vision science is ‘shading’. It is discussed in terms of an inverse optics algorithm known as ‘shape from shading’. However, the familiar techniques of the visual arts count many alternative cues for the articulation of pictorial relief. From an art technical perspective these cues are well known. Although serving a similar purpose as shading proper, they allow a much flatter value scale, making it easier to retain the picture plane, or major tonal areas. Vision research has generally ignored such methods, possibly because they lack an obvious basis in ecological optics. We attempt to rate the power of various techniques on a common ‘shading scale’. We find that naive observers spontaneously use a variety of cues, and that several of these easily equal, or beat, conventional shading. This is of some conceptual interest to vision science, because shading has a generally acknowledged ecological basis, whereas the alternative methods lack this.

“Exocentric pointing in the visual field” involves the setting of a pointer so as to visually point to a target, where both pointer and target are objects in the visual field. Phenomenologically,such pointings show systematic deviations from veridicality of several degrees. The errors are very small in the vertical and horizontal directions, but appreciable in oblique directions. The magnitude of the error is largely independent of the distance between pointer and target for stretches in the range 2–27º. A general conclusion is that the visual field cannot be described in terms of one of the classical homogeneous spaces, or, alternatively, that the results from pointing involve mechanisms that come after geometry proper has been established. ispartof: i-Perception vol:4 issue:8 pages:532-542 ispartof: location:United States status: published

When a light source moves, the isophotes of the illuminance field (observed as “shading” in the case of Lambertian surfaces) move over the surfaces of illuminated objects. The sense of rotation of the isophotes relative to the sense of rotation of the “surface illuminance flow,” that is the tangential component of the illumination direction over the surface, depends on the Gaussian curvature of the surface. The temporal change of orientation, the “shading twist,” reveals this purely surface related quality. Since the shading twist depends only on the local curvature of the surface it doesn’t matter at all how the light source moves or where the light sources are, the “shading twist” is a pure surface property, that is to say, it behaves as being painted upon the surface. The formal relations pertaining to the shading twist are analyzed and a numerical simulation is presented that fully corroborates the conclusions from the formal study. The algorithm is also tested on a real scene.

SFS (Shape From Shading) theory is based upon the Lambertian paradigm. Our visual demonstrations imply that this paradigm fails to apply to the conventional stimuli used to probe vision. ispartof: i-Perception vol:4 issue:5 pages:299-302 ispartof: location:United States status: published

We study the “color weight” for a number of rather different paradigms. In well researched heterochromatic photometry methods we find that the “weights” determined by settings of naive observers are closely determined by the CIE luminance functional. This is very different for tasks that involve mid- and high-level aspects of perception. In several cases we find equipollence for the display red, green and blue channels. Moreover, in such cases the very nonlinear maximum-rule fits the data rather better than a linear functional. These findings are of interest when photometry needs to be applied for stimuli that are different from the high temporal and low spatial frequency gratings typical for flicker photometry. These results are relevant for science, ergonomics and art.

Cartoon-style line drawings contain very condensed information, after all most of the page stays blank. Yet, they constrain the contents of immediate visual awareness to an extraordinary extent. This is true even for drawings that are - though nominally "representational" - not even in central projection. Moreover, the strokes used in a drawing may stand for a bewildering variety of entities in the world. We studied Picasso drawings from the 1940s in which the artist famously combined multiple viewpoints. We find that the pictorial reliefs obtained from various observers agree to a large extent, and that the differences are of a very specific nature, typically involving variations in the mutual spatial attitudes of rigid body parts in figure studies. Although the purely planar layout of the drawings accounts for much of visual awareness, observers also use the sparse depth cues provided by the artist to evoke volumetric impressions. Observers also freely insert "template knowledge" about the structure of familiar generic objects. ispartof: Cognition vol:125 issue:3 pages:394-412 ispartof: location:Netherlands status: published

The shading cue is supposed to be a major factor in monocular stereopsis. However, the hypothesis is hardly corroborated by available data. For instance, the conventional stimulus used in perception research, which involves a circular disk with monotonic luminance gradient on a uniform surround, is theoretically 'explained' by any quadric surface, including spherical caps or cups (the conventional response categories), cylindrical ruts or ridges, and saddle surfaces. Whereas cylindrical ruts or ridges are reported when the outline is changed from circular to square, saddle surfaces are never reported. We introduce a method that allows us to differentiate between such possible responses. We report observations on a number of variations of the conventional stimulus, including variations of shape and quality of the boundary, and contexts that allow the observer to infer illumination direction. We find strong and expected influences of outline shape, but, perhaps surprisingly, we fail to find any influence of context, and only partial influence of outline quality. Moreover, we report appreciable differences within the generic population. We trace some of the idiosyncrasies (as compared to shape from shading algorithms) of the human observer to generic properties of the environment, in particular the fact that many objects are limited in size and elliptically convex over most of their boundaries. ispartof: i-Perception vol:1 issue:3 pages:159-178 ispartof: location:United States status: published

The issue of the existence of planes-understood as the carriers of a nexus of straight lines-in the monocular visual space of a stationary human observer has never been addressed. The most recent empirical data apply to binocular visual space and date from the 1960s (Foley, 1964). This appears to be both the first and the last time this basic issue was addressed empirically. Yet the question is of considerable conceptual interest. Here we report on a direct empirical test of the existence of planes in monocular visual space for a group of sixteen experienced observers. For the majority of these observers monocular visual space lacks a projective structure, albeit in qualitatively different ways. This greatly reduces the set of viable geometrical models. For example, it rules out all the classical homogeneous spaces (the Cayley-Klein geometries) such as the familiar Luneburg model. The qualitatively different behavior of experienced observers implies that the generic population might well be inhomogeneous with respect to the structure of visual space.

Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer.

Background: Increased insulin-like growth factor (IGF)-I and IGF-II concentrations are related to increased colorectal cancer risk. Isoflavones have been associated with reduced colorectal cancer risk, and may affect the IGF system because of their weak estrogenic activity. The aim of the study was to investigate the effect of isolated isoflavones on serum concentrations of IGF system components.Materials and Methods: We conducted a randomized, placebo-controlled, double-blinded, crossover trial in four hospitals in the Netherlands to investigate the effect of an 8-week supplementation with red clover–derived isoflavones (84 mg/d) on serum IGF-I concentrations. In addition, serum concentrations of IGF-II and IGF binding proteins (IGFBP)-1, IGFBP-2, and IGFBP-3 were assessed. Normal colorectal tissue biopsies were obtained after the first intervention period and mRNA expression of IGF-I, IGF-II, IGFBP-3, and IGF-IR was evaluated. Our study population consisted of 34 postmenopausal women with a family history of colorectal cancer or a personal history of colorectal adenomas.Results: Isoflavone supplementation did not significantly affect serum concentrations of total IGF-I (mean relative within-person difference; IGF-I, −2.0%; 95% confidence interval, −8.0% to 3.9%). IGF-II and IGFBPs were also not significantly altered after isoflavone supplementation. Colorectal tissue mRNA expression of IGF system components did not significantly differ between individuals on isoflavone supplementation and those who received placebo.Conclusions: The results of our trial, supported by a qualitative review of soy trials published to date, suggest that isoflavones do not significantly affect circulating levels of IGF system components. Increased levels of IGF-I, as observed in most of these trials, are likely due to simultaneous protein supplementation. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2585–93)

Background: Drotrecogin alfa activated (DrotAA) is licensed for treatment of patients with severe sepsis and organ failure. Among the latter, acute kidney injury (AKI), defined as the persistence of oligo-anuria following adequate resuscitation, is one of the most apprehended. We conducted a prospective, observational, and controlled study to test the hypothesis that DrotAA beneficially affected the evolution and outcome of AKI, complicating acute sepsis-induced cardiopulmonary failure. Methods: Forty-six patients were studied. Thirty subjects received standard treatment for sepsis without DrotAA. In the remaining 16 patients, DrotAA was added as a continuous infusion of 24 mg/kg/h for 96 h. Results: Mean age, causes of sepsis, and severity/organ failure scores were comparable between patients treated with or without DrotAA. Mortality at 28 days was high and comparable between both treatment groups (56% vs. 69%, DrotAA vs. no DrotAA; P 5 0.5). When oligo-anuria was present at the start of the study, it persisted during treatment in all patients, with no significant difference between groups. Both treatment groups presented with baseline mean daily fractional excretion of sodium values 42% that remained high during the observation period, regardless of whether DrotAA was given or not. Kidney histology showed a preserved renal architecture with tubular necrosis in all specimens. Similar glomerular, tubulo-interstitial, and vascular alterations were present in both treatment groups. Conclusion: In this small cohort of patients with severe sepsis who received adjuvant DrotAA treatment, no effect on urine output, tubular function, or mortality could be demonstrated.

An exocentric pointing task was used to compare the indicated pointing directions under exchange of target and pointer. Such a pair of pointing directions, together with the pointer and target locations, specifies a unique cubic arc. Such an arc may assume one of two qualitatively different shapes, namely a ‘‘C-arc’’ (constant sign of curvature) or an ‘‘S-arc’’ (containing a point of inflection between the endpoints). We show that human observers most often produce S-curves. This is of fundamental importance, since—in case one interprets the curve as an empirically determined ‘‘pregeodesic’’ (‘‘shortest connection’’, or ‘‘straight’’ connection in visual space)—it would imply that ‘‘visual space’’ in the strict geometrical sense is a non-entity. The experiments were performed in the outside environment, under normal daylight conditions, for distances ranging from one to over thirty meters. The implications of these data are discussed and possible ways to extend the restricted notion of ‘‘visual space’’ (e.g., as advocated by Luneburg) such as to allow one to account for the present results are suggested. Such extensions of the visual space concept include the local adjustment of geometrical structure in regions adjacent to the fixation direction.

ContextAcid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown.ObjectiveTo investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers.SubjectsThree short Kurdish brothers and their relatives.ResultsThe index cases presented with short stature, microcephaly, and low circulating IGF-I and IGF-binding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives.ConclusionsThe clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect.

What are "natural parts" of pictorial reliefs? Intuitively, and suggested by common lore from the visual arts, they are the bulges that stick out toward the observer. Each such bulge contains a (locally) nearest point and is bounded by one or (usually) more curvilinear ruts. The latter meet in "passes" or saddle points. This divides the relief into "natural districts". From a formal analysis one knows that reliefs can be divided into "hill districts" or "dale districts", these two "natural" parcellations being fully distinct. We report empirical results that strongly suggest that visual awareness is based on a partition in bulges, which are mutually only weakly connected. Such a notion immediately explains why inverted reliefs or surfaces illuminated from below appear so different as to be mutually not recognizable. ispartof: i-Perception vol:6 issue:6 pages:1-21 ispartof: location:United States status: published

We report final event-driven analysis data on the immunogenicity and efficacy of the human papillomavirus 16 and 18 ((HPV-16/18) AS04-adjuvanted vaccine in young women aged 15 to 25 years from the PApilloma TRIal against Cancer In young Adults (PATRICIA). The total vaccinated cohort (TVC) included all randomized participants who received at least one vaccine dose (vaccine, n = 9,319; control, n = 9,325) at months 0, 1, and/or 6. The TVC-naive (vaccine, n = 5,822; control, n = 5,819) had no evidence of high-risk HPV infection at baseline, approximating adolescent girls targeted by most HPV vaccination programs. Mean follow-up was approximately 39 months after the first vaccine dose in each cohort. At baseline, 26% of women in the TVC had evidence of past and/or current HPV-16/18 infection. HPV-16 and HPV-18 antibody titers postvaccination tended to be higher among 15- to 17-year-olds than among 18- to 25-year-olds. In the TVC, vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or greater (CIN1+), CIN2+, and CIN3+ associated with HPV-16/18 was 55.5% (96.1% confidence interval [CI], 43.2, 65.3), 52.8% (37.5, 64.7), and 33.6% (−1.1, 56.9). VE against CIN1+, CIN2+, and CIN3+ irrespective of HPV DNA was 21.7% (10.7, 31.4), 30.4% (16.4, 42.1), and 33.4% (9.1, 51.5) and was consistently significant only in 15- to 17-year-old women (27.4% [10.8, 40.9], 41.8% [22.3, 56.7], and 55.8% [19.2, 76.9]). In the TVC-naive, VE against CIN1+, CIN2+, and CIN3+ associated with HPV-16/18 was 96.5% (89.0, 99.4), 98.4% (90.4, 100), and 100% (64.7, 100), and irrespective of HPV DNA it was 50.1% (35.9, 61.4), 70.2% (54.7, 80.9), and 87.0% (54.9, 97.7). VE against 12-month persistent infection with HPV-16/18 was 89.9% (84.0, 94.0), and that against HPV-31/33/45/51 was 49.0% (34.7, 60.3). In conclusion, vaccinating adolescents before sexual debut has a substantial impact on the overall incidence of high-grade cervical abnormalities, and catch-up vaccination up to 18 years of age is most likely effective. (This study has been registered at ClinicalTrials.gov under registration no. NCT001226810.)

Context: Children with Prader-Willi syndrome (PWS) attain high-serum immunoreactive IGF-1 levels during a standard-dose GH treatment, which leads to concern, but lowering the dose deteriorates their body composition. Objective: The objective of the study was to evaluate serum IGF-1, IGF binding protein (IGFBP)-3, and acid-labile subunit (ALS) levels, complex formation, and IGF bioactivity in GH-treated PWS children. Design: This was a cross-sectional study. Setting: The setting of the study was a Dutch PWS cohort. Participants: Forty GH-treated PWS children compared with 41 age- and sex-matched healthy controls participated in the study. Interventions: Interventions included GH treatment (1.0 mg/m2·d = ∼0.035 mg/kg·d). Main Outcome Measures: Serum IGF-1, IGFBP-3, and ALS levels, complex formation, and IGF bioactivity by IGF-1 receptor kinase activation assay were measured. Results: Serum IGF-1, IGFBP-3, and ALS levels and IGF-1 to IGFBP-3 ratio were significantly higher in GH-treated PWS children than in healthy controls. The 150-kDa ternary complex formation was, however, also significantly higher than in controls, indicating that most of serum IGF-1 is sequestered in the ternary 150-kDa complex with ALS and IGFBP-3. Young GH-treated PWS children [median (interquartile range) aged 5.2 (4.3-7.2) y] exhibited higher serum IGF bioactivity than controls, but no difference was observed in IGF bioactivity between older GH-treated PWS children, aged 14.9 (13.8-16.2) years, and controls. The proportion of IGF bioactivity of total serum IGF-1 was, however, lower in GH-treated PWS children than in controls. Serum immunoreactive IGF-1 levels did not correlate with IGF bioactivity in GH-treated children with PWS, in contrast to a strong positive correlation in healthy controls. Conclusions: In GH-treated PWS children, most serum IGF-1 is sequestered in the 150-kDa complex. Higher IGF bioactivity was found only in young GH-treated PWS children and not in the older ones. IGF bioactivity during GH showed a wide variation, and there was a disrupted correlation with immunoreactive IGF-1 levels, which makes immunoreactive IGF-1 levels an inappropriate indicator for GH dosing in PWS children.