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The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood. Here, we have analysed whole blood samples serially collected from 40 surviving COVID-19 patients throughout their recovery in ICU using high-dimensional cytometry by time-of-flight (CyTOF) and cytokine multiplexing. Based on the neutrophil-to-lymphocyte ratio (NLR), we defined four sequential immunotypes during recovery that correlated to various clinical parameters, including the level of respiratory support at concomitant sampling times. We identified classical monocytes as the first immune cell type to recover by restoration of HLA-DR-positivity and the reduction of immunosuppressive CD163 + monocytes, followed by the recovery of CD8 + and CD4 + T cell and non-classical monocyte populations. The identified immunotypes also correlated to aberrant cytokine and acute-phase reactant levels. Finally, integrative analysis of cytokines and immune cell profiles showed a shift from an initially dysregulated immune response to a more coordinated immunogenic interplay, highlighting the importance of longitudinal sampling to understand the pathophysiology underlying recovery from severe COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-021-03808-8.

Tumoural-CD8+T cells exhibit exhausted or dysfunctional states. Contrary to immunotherapy-responsive exhausted-CD8+T cells, the clinical features of dysfunctional-CD8+T cells are disputed. Hence, we conducted large-scale multi-omics and multi-dimensional mapping of CD8+T cell-states across multiple cancer patient-cohorts. This identified tumour-specific continuum of CD8+T cell-states across 6 human cancers, partly imprinted by organ-specific immuno-modulatory niches. Herein, melanoma and glioblastoma enriched prototypical exhausted (CD8+TEXT) and severely-dysfunctional (CD8+TSDF) states, respectively. Contrary to CD8+TEXT, CD8+TSDF displayed transcriptomic and epigenetic effector/cytolytic dysfunctions, and dysregulated effector/memory single-cell trajectories, culminating into maladaptive prodeath stress and cell-cycle defects. Suboptimal antigen-priming underscored CD8+TSDF, which was distinct from immune-checkpoints “rich” CD8+TEXT, reflecting chronic antigen-stimulation. Continuum variation also existed on tumour spatial-level, with convergent (CD8+TEXT-supportive vascular regions) and divergent features (dysfunctional CD4+T::CD8+TSDFcell-to-cell interactions) between melanoma and glioblastoma. Globally, IFNγ-IL2 disparities, paucity of intra-tumoural CD4+/CD8+T cells, and myeloid TGFβ/wound healing responses, distinguished CD8+TSDF-landscape. Within immuno-oncology clinical-trials, anti-PD1 immunotherapy failed to “reinvigorate” CD8+TSDF-landscape, and instead facilitated effector-dysfunction and TGFβ/wound healing. However, cellular immunotherapies (dendritic cell-vaccines, adoptive T-cell therapy) ameliorated assorted CD8+TSDF-landscape disparities, highlighting a roadmap for anti-glioblastoma multimodal-immunotherapy. Collectively, our study comprehensively expands clinical-knowledge on CD8+T cell-exhaustion and suggests that tumour-specific, pre-existing CD8+TEXT/TSDF-states, determine immunotherapy-responses.

Background Glioblastoma Multiforme (GBM) remains the most common malignant primary brain tumor with a dismal prognosis that rarely exceeds beyond two years despite extensive therapy, which consists of maximal safe surgical resection, radiotherapy and/or chemotherapy. Recently, it has become clear that GBM is not one homogeneous entity and that both intra-and intertumoral heterogeneity contribute significantly to differences in tumoral behavior which may consequently be responsible for differences in survival. Strikingly and in spite of its dismal prognosis, small fractions of GBM patients seem to display extended survival compared to the large majority of patients. The underlying mechanisms for this peculiarity remain largely unknown however, even though emerging data suggest that both cancer cell-autonomous and microenvironmental factors and their interplay probably play an important role. Material and Methods We used high-dimensional, multiplexed immunohistochemistry to spatially, and cytometry by time-of-flight to quantitively characterize the cell constitution and interactions within the tumor microenvironment (TME) in 21 extreme long-term survivors (living over ten years since primary diagnosis or five years after recurrence) and 42 deeply matched short-term controls (living under 1.5 year) on a single cell level. For all tumors (epi-)genetic data was also collected. Results We identified a high level of both inter-and intrapatient heterogeneity defined by several distinct tumor niches, as well as described interactions within these niches and with the surrounding infiltrating immune cells of the TME. By linking patient characteristics with the heterogeneous immune composition we are building an immune stratification that can be linked to patient survival in GBM. Conclusion Generating an immune stratification for GBM will allow us to identify immune characteristics responsible for longer or even exceptional survival, as well as thoroughly identify tumor components that may serve as a potential target for personalized treatment strategies. Therefore, this study is also an essential initial step towards such clinical trials which alter the TME in a favorable way with a personalized modulation strategy.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity., The host immune response plays a critical role in the immunopathology of SARS-CoV2. Here the authors combine a systems biology approach to implicate monocytes as key drivers of cytokine storm and disturbed neutrophil activation in COVID-19 disease severity.

In malignant cancer, excessive amounts of mutant p53 often lead to its aggregation, a feature that was recently identified as druggable. Here, we describe that the induction of a heat-shock response by Foldlin, a small-molecule tool compound, reduced the protein levels of misfolded/aggregated mutant p53 while contact mutants or wild-type p53 remained largely unaffected. Foldlin also prevented the formation of stress-induced p53 nuclear inclusion bodies. In spite of our inability to identify a specific molecular target, Foldlin also reduced protein levels of aggregating SOD1 variants. Finally, by screening a library of 778 FDA-approved compounds for their ability to reduce misfolded mutant p53, we identified the proteasome inhibitor Bortezomib with similar cellular effects as Foldlin. Overall, the induction of a cellular heat shock response seems an effective strategy to deal with pathological protein aggregation. It remains to be seen however, how this strategy can be translated to a clinical setting.

Scope: The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. Methods: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. Recommendations: The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints. © 2019 The Authors

Aortocaval fistulas are a rare and potentially life-threatening complication of aortic aneurysms. They pose a significant diagnostic challenge due to their aspecific presentation. We describe two cases of patients who were admitted to the emergency room with an unusual presentation. The first patient was a 69-year-old male, with a history of hypertension and hyperlipidemia, who was admitted to our hospital with a painful and swollen left leg. The second patient was a 75-year-old male with a history of coronary artery bypass graft and cholecystectomy who was admitted due to a swollen left leg and dyspnea. We also give a review of the literature regarding the clinical presentation, diagnosis and management of aortocaval fistulas.

Objective: To assess between-hospital variations in standardized in-hospital mortality ratios of community-acquired pneumonia (CAP), and identify possible leads for quality improvement. Design: We used an administrative database to estimate standardized in-hospital mortality ratios for 111 Belgian hospitals, by carrying out a set of hierarchical logistic regression models, intended to disentangle therapeutic attitudes and biases. To facilitate the detection of false-negative/positive results, we added an inconclusive zone to the funnel plots, derived from the results of the study. Data quality was validated by comparison with (i) alternative data from the largest Belgian Sickness Fund, (ii) published German hospital data and (iii) the results of an on-site audit. Setting: All Belgian hospital discharge records from 2004 to 2007. Study participants: A total of 111 776 adult patients were admitted for CAP. Main outcome measure: Risk-adjusted standardized in-hospital mortality ratios. Results: Out of the 111 hospitals, we identified five and six outlying hospitals, with standardized mortality ratios of CAP consistently on the extremes of the distribution, as providing possibly better or worse care, respectively, and 18 other hospitals as having possible quality weaknesses/strengths. At the individuals' level of the analysis, adjusted odds ratios showed the paramount importance of old age, comorbidity and mechanical ventilation. The data compared well with the different validation sources. Conclusions: Despite the limitations inherent to administrative data, it seemed possible to establish inter-hospital differences in standardized in-hospital mortality ratios of CAP and to identify leads for quality improvement. Monitoring is needed to assess progress in quality.

25th International Conference on Optical Fiber Sensors, 2017, Jeju, Corea del Sur., This paper presents the first report on on-line and final blind field test results of a pipeline integrity threat surveillance system. The system integrates a machine+activity identification mode, and a threat detection mode. Two different pipeline sections were selected for the blind tests: One close to the sensor position, and the other 35 km away from it. Results of the machine+activity identification mode showed that about 46% of the times the machine, the activity or both were correctly identified. For the threat detection mode, 8 out of 10 threats were correctly detected, with 1 false alarm., European Commission, Ministerio de Economía y Competitividad, Comunidad de Madrid

24th International Conference on Optical Fibre Sensors, Curitiba, Brazil, September 28, 2015., The preliminary results of a surveillance system set up for real time monitoring activities along a pipeline and analyzing for possible threats are presented. The system consists of a phi-OTDR based sensor used to monitor vibrations along an optical fiber combined with a pattern recognition system that classifies the recorded signals. The acoustic traces generated by the activities of different machines at various locations along a pipeline were recorded in the field. The signals, corresponding to machinery activities, were clearly distinguished from background noise. A threat classification rate of 68.11% with 55.55% false alarms was obtained., European Commission, Ministerio de Economía y Competitividad, Comunidad de Madrid, Universidad de Alcalá, Ministerio de Ciencia e Innovación

Objectives Various serum human chorionic gonadotropin (hCG) discriminatory zones are currently used for evaluating the likelihood of an ectopic pregnancy in women classified as having a pregnancy of unknown location (PUL) following a transvaginal ultrasound examination. We evaluated the diagnostic accuracy of discriminatory zones for serum hCG levels of > 1000 IU/L, 1500 IU/L and 2000 IU/L for the detection of ectopic pregnancy in such women. Methods This was a prospective observational study of women who were assessed in a specialized transvaginal scanning unit. All women with a PUL had serum hCG measured at presentation. Expectant management of PULs was adopted. These women were followed up with transvaginal ultrasound, monitoring of serum hormone levels and laparoscopy until a final diagnosis was established: a failing PUL, an intrauterine pregnancy (IUP), an ectopic pregnancy or a persisting PUL. The persisting PULs probably represented ectopic pregnancies which had been missed on ultrasound and these were incorporated into the ectopic pregnancy group. Three different discriminatory zones (1000 IU/L, 1500 IU/L and 2000 IU/L) were evaluated for predicting ectopic pregnancy in this PUL population. Results A total of 5544 consecutive women presented to the early pregnancy unit between 25 June 2001 and 14 April 2003. Of these, 569 (10.3%) women were classified as having a PUL, 42 of which were lost to follow up. Of the 527 (9.5%) cases with PUL analyzed, there were 300 (56.9%) failing PULs, 181 (34.3%) IUPs and 46 (8.7%) ectopic pregnancies. Overall, 74.6% were symptomatic and 25.4% were asymptomatic (P = 8.825E–07). The sensitivity and specificity of an hCG level of > 1000 IU/L to detect ectopic pregnancy were 21.7% (10/46) and 87.3% (420/481), respectively; for an hCG level of > 1500 IU/L these values were 15.2% (7/46) and 93.4% (449/481), respectively, and for an hCG level of > 2000 IU/L they were 10.9% (5/46) and 95.2% (458/481), respectively. Conclusions Varying the discriminatory zone does not significantly improve the detection of ectopic pregnancy in a PUL population. A single measurement of serum hCG is not only potentially falsely reassuring but also unhelpful in excluding the presence of an ectopic pregnancy. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.

Objective To describe the gray-scale sonographic and color Doppler imaging features of the most common histopathological subtypes of borderline ovarian tumors. Methods We analyzed retrospectively the preoperative transvaginal sonographic reports of patients with a histological diagnosis of borderline ovarian tumor. All patients were scanned consecutively by two of the investigators using transabdominal and transvaginal gray-scale imaging to assess the morphology and color Doppler to obtain indices of the blood flow. Sonographic findings were compared to histopathological data. Results A total of 113 consecutive cases were reviewed from two referral centers for gynecological oncology. At histological examination 50 tumors (44%) were classified as being serous borderline ovarian tumors (SBOT), 61 (54%) were mucinous borderline ovarian tumors (MBOT) (42 intestinal type and 19 endocervical type), and two patients (2%) presented with borderline endometrioid tumors. SBOTs and endocervical-type MBOTs had very similar sonographic features and a smaller diameter, fewer locules (usually unilocular-solid lesions) and a higher color score than intestinal-type MBOTs. Intestinal-type MBOTs were characterized by a significantly higher percentage of lesions with > 10 locules when compared with the endocervical-type MBOTs. Conclusion Intestinal-type MBOTs have different sonographic features from other common borderline ovarian tumors. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.

Using microarrays is a powerful technique to monitor the expression of thousands of genes in a single experiment. From series of such experiments, it is possible to identify the mechanisms that govern the activation of genes in an organism. Short deoxyribonucleic acid patterns (called binding sites) near the genes serve as switches that control gene expression. As a result similar patterns of expression can correspond to similar binding site patterns. Here we integrate clustering of coexpressed genes with the discovery of binding motifs. We overview several important clustering techniques and present a clustering algorithm (called adaptive quality-based clustering), which we have developed to address several shortcomings of existing methods. We overview the different techniques for motif finding, in particular the technique of Gibbs sampling, and we present several extensions of this technique in our Motif Sampler. Finally, we present an integrated web tool called INCLUSive (available online at http://www.esat.kuleuven.ac.be//spl sim/dna/BioI/Software.html) that allows the easy analysis of microarray data for motif finding.

OBJECTIVE: To determine if power Doppler ultrasound examination of the endometrium can contribute to a correct diagnosis of endometrial malignancy in women with postmenopausal bleeding and endometrium >/= 5 mm. METHODS: Eighty-three women with postmenopausal bleeding and endometrium >/= 5 mm underwent gray-scale and power Doppler ultrasound examination using predetermined, standardized settings. Suspicion of endometrial malignancy at gray-scale ultrasound examination (endometrial morphology) was noted, and the color content of the endometrium at power Doppler examination was estimated subjectively (endometrial color score). Computer analysis of the most vascularized area of the endometrium was done off-line in a standardized manner. Stepwise multivariate logistic regression analysis was carried out to determine which subjective and objective ultrasound and power Doppler variables satisfied the criteria to be included in a model to calculate the probability of endometrial malignancy. RESULTS: Endometrial thickness, vascularity index (vascularized area/endometrial area), and use of hormone replacement therapy (HRT) satisfied the criteria to be included in the model used to calculate the 'objective probability of endometrial malignancy'. Endometrial morphology, endometrial color score and HRT use satisfied the criteria to be included in the model to calculate the 'subjective probability of malignancy'. Endometrial thickness >/= 10.5 mm had a sensitivity with regard to endometrial cancer of 0.88 and a specificity of 0.61. At a fixed sensitivity of 0.88, the specificity of the 'objective probability of malignancy' (0.81) was superior to all other ultrasound and power Doppler variables (P = 0.001-0.02). The 'objective probability of malignancy' detected more malignancies at endometrium 5-15 mm than endometrial morphology (5/7 vs. 1/7, i.e. 0.71 vs. 0.14; P = 0.125) with a similar specificity (49/57 vs. 51/57, i.e. 0.86 vs. 0.89). CONCLUSION: Power Doppler ultrasound can contribute to a correct diagnosis of endometrial malignancy, especially if the endometrium measures 5-15 mm. The use of regression models including power Doppler results to estimate the risk of endometrial cancer deserves further development. (Less)

BACKGROUND: Recent progress in predictive techniques allows people at risk of developing type 1 diabetes to be identified in a pre-symptomatic stage and prevention trials to be implemented. The present study examined prospectively whether participants in a screening programme anticipated behavioural changes in the event of having a high risk. METHODS: Four hundred and three first-degree relatives of people with type 1 diabetes completed a self-administered questionnaire about their views on screening and diabetes, and questionnaires on well-being and locus of control. RESULTS: Prior to risk notification, 73% reported that they intended to introduce lifestyle changes if at high risk. The vast majority of the respondents (87%) reported that eating habits would be the main changes made. Those anticipating changes believed they could take actions to reduce their risk of type 1 diabetes (p

The purpose of this work is to examine critically the correlations between ionization potential or absolute hardness and the catalytic behavior of binary and ternary oxides containing lanthanides (Ln) in alkene oxidation. Five lanthanide oxides (La2O3, Sm2O3, Pr6O11, Tb4O7, and CeO2) and three praseodymium molybdates (Pr-2-Mo3O12, Pr6MoO12, and Pr2MoO6, were used as pure phases or in mixtures with MoO3 in the partial and total oxidation of isobutene. The catalytic performances of their mixtures with MoO3 are described in the context of the "remote control mechanism", according to which the lanthanide-based oxides are identified as donors of spillover oxygen. Their donor ability is evaluated through the synergetic effects on methacrolein selectivity and correlated with the physical properties mentioned above. In the case of ternary oxides such as praseodymium molybdates, the concepts of average ionization energy and average absolute hardness are proposed to take into account the fact that the electron density and therefore the reactivity of mobile surface oxygen species are influenced by the presence of both metals in the lattice. The results obtained with the pure Ln-based oxides are in line with the literature concepts of ionization energy and absolute hardness. As far as the mechanical mixtures are concerned, it is shown that the above correlations, when combined with the "remote control" concepts, provide a comprehensive view of the influence of ionization energy or absolute hardness for both single phase and biphasic catalysts exhibiting phase cooperation.

One-step non-hydrolytic condensation reactions, starting from VO(O i Pr) 3 and NbCl 5 , have been used for the first time to prepare Nb-V oxide catalysts. Different materials containing the NbVO 5 phase at different purity levels have been obtained, after thermal treatments, depending on the experimental conditions. The synthetic procedure has also been applied to prepare ternary Nb-V-Si oxide systems. From preliminary catalytic reaction studies it appears that the catalysts so prepared are promising with respect to their interesting performances in the oxidative dehydrogenation (ODH) of propane. It has also been found that α-Sb 2 O 4 , physically blended with the Nb-V oxide materials, could act as an appropriate promoter to improve the catalytic performances of these systems.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and scanning electron microscopy are used to prove that the ultrasound used for the preparation of molybdenum- and praseodymium-based heterogeneous multiphase catalysts can induce solid-state reactions at room. temperature between the binary oxides Pr6O11 and MoO3. Turbulent flows and shock waves produced by the ultrasonic cavitation are thought to cause particles to collide into one another and to generate local temperatures which are sufficiently high far inducing interparticle melting. Unequivocal evidence is provided by ToF-SIMS that the ultrasonic dispersion leads to the surface formation of the praseodymium molybdate phase Pr2Mo3O12.

The catalytic role played by praseodymium molybdate phases (Pr6MoO12, Pr2MoO6, Pr2Mo3O12) generated in Pr6O11-MoO3 catalysts during their use in the selective oxidation of isobutene to methacrolein is evaluated in order to determine whether the observed synergetic effects have to be assigned to cooperation between binary praseodymium and molybdenum oxides, or to the occurrence of praseodymium molybdate phases, that would be catalytically active themselves or would act synergetically with MoO3 or Pr6O11 X-ray diffraction, infrared spectroscopy, X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry (ToF SIMS) are used to determine the composition of the used Pr6O11-MoO3 catalysts. Pr6MoO12 appears to be the major ternary phase present in the bulk and Pr2Mo3O12 is predominant at the surface. To understand the catalytic behaviour of the Pr6O11-MoO3 mixtures, the catalytic performances of the pure praseodymium molybdate phases and those of their mixtures with MoO3, Sb2O4 and Pr6O11 were also examined. It is shown that the cooperative effects previously observed in the MoO3-Pr6O11 mixtures most probably cannot be assigned exclusively to the intrinsic catalytic properties of praseodymium molybdates. A cooperation is also observed between other couples of oxide phases, i.e. Pr6MoO12 displays donor properties with respect to MoO3. It appears also that the evolution of the catalytic properties of Pr6MoO12-MoO3 mixtures with respect to the Pr/Mo content is completely different from the one observed in MoO3-Pr6O11 mixtures. In addition, it does not seem that the observed synergetic effects could be assigned to the simultaneous presence of ternary PrxMoyOz phases and Pr6O11. The generation of praseodymium molybdate phases during the catalytic tests seems therefore to play no significant role in the catalytic behaviour of MoO3-Pr6O11 mixtures. (C) 1998 Elsevier Science B.V. All rights reserved.

In our 15-bed neonatal intensive care unit (NICU), four new-borns were found to be colonized or infected with Pseudomonas aeruginosa within a period of one week. To identify the outbreak source, three independent studies were performed: epidemiological investigation, environmental surveillance and genotypic typing of isolates. Although epidemiological investigation by a case—control study revealed no conclusive results, the transfusion of fresh frozen plasma (FFP) and human albumin (HA) appeared to be the factor with highest risk. Environmental surveillance and random amplification of polymorphic DNA (RAPD) of isolates identified a water-bath used to warm FFP and HA as the likely reservoir for the outbreak. Further spread of the organism did not occur after elimination of this water-bath from the NICU. RAPD identified in addition an isolate from an infant hospitalized in the NICU five months before the outbreak with a pattern matching the one of the outbreak cluster.

Time-of-flight secondary ion mass spectrometry (TOF SIMS) analyses have been performed on MoO3–Pr6O11 mixtures before and after their use in the selective oxidation of isobutene to methacrolein at 673 K. The three pure molybdate phases (Pr2MoO6, Pr2Mo3O12, Pr6MoO12) obtained independently by the citrate route have also been examined to determine their respective SIMS fragmentation patterns. Although the Pr2MoO6 and Pr2Mo3O12 phases were found to give the same molecular fragments, these phases could be distinguished by the relative intensity ratios of some particular species. Identification of Pr6MoO12 was easier owing to the presence of characteristic high-mass mixed Pr–Mo fragments. A linear relationship was observed when plotting the experimental intensity ratios of several molecular fragments against the Pr/Mo bulk composition. The same behaviour was also noticed for a series of Pr6O11–MoO3 mixtures. Moreover, the examination of the 3-D crystal structure of the pure molybdate phases indicates that the fragmentation patterns of these phases were directly related to their structure. As far as the used catalysts were concerned, the SIMS results showed that: (i) the experimental intensity ratios of given fragments were much smaller in the used catalysts than in the fresh ones; (ii) fragments characteristic of the Pr6MoO12 phase were absent; and (iii) differences in the relative SIMS intensities of certain fragments showed the dominant presence of the Pr2Mo3O12 phase.

Several bismuth(III) carboxylates (formate, acetate, propionate, oxalate, lactate) and the analogous tervalent lanthanum, samarium and praseodymium formates and acetates were synthesized and characterized in view of their use as precursors for the formation of bismuth- or lanthanide-based molybdate catalysts upon controlled thermal decomposition on MoO3 support. Mixed Bi-Ln carboxylates were prepared and used in parallel as precursors for Ln-promoted bismuth molybdate catalysts. Both the nature of the lanthanide element and the calcination temperature were found to determine the formation of specific molybdate-type phases on the support. Detailed examination of these catalysts by X-ray diffraction and FTIR spectroscopy identified alpha-M(2)Mo(3)O(12) phases in Bi- and Pr-containing samples calcined at 823 K, and hexamolybdate phases M(2)Mo(6)O(21) in La- or Sm-containing catalysts calcined at 973 K.

SUMMARYVaricella-zoster virus causes chickenpox (CP) and after reactivation herpes zoster (HZ). Vaccines are available against both diseases warranting an assessment of the pre-vaccination burden of disease. We collected data from relevant Belgian databases and performed five surveys of CP and HZ patients. The rates at which a general practitioner is visited at least once for CP and HZ are 346 and 378/100 000 person-years, respectively. The average CP and HZ hospitalization rates are 5·3 and 14·2/100 000 person-years respectively. The direct medical cost for HZ is about twice as large as the direct medical cost for CP. The quality-adjusted life years lost for ambulatory CP patients consulting a physician is more than double that of those not consulting a physician (0·010vs. 0·004). In conclusion, both diseases cause a substantial burden in Belgium.

The differential cross section for the [sup 16]O([gamma],[ital p][sub 0])[sup 15]N reaction has been investigated at photon energies [ital E][sub [gamma]] between 33 and 69 MeV using a bremsstrahlung beam; angular distributions at laboratory angles of 30[degree], 45[degree], 60[degree], 75[degree], 90[degree], and 120[degree] were extracted from the tip region of the photoproton spectra when stepping the end point in 4 MeV intervals. The data are compared with calculations based on a self-consistent microscopic approach.

A new, improved method to define the random particle energy spectrum in tagged photon experiments is described. This procedure yields the random spectrum with very good statistical accuracy, and can be applied when no hard coincidence with the focal plane is required in order to accept events.

Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. The aim of this study was to evaluate the combined performance of six potential plasma biomarkers in the diagnosis of endometriosis.This case-control study was conducted in 294 infertile women, consisting of 93 women with a normal pelvis and 201 women with endometriosis. We measured plasma concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive protein (hsCRP), and cancer antigens CA-125 and CA-19-9. Analyses were done using the Kruskal-Wallis test, Mann-Whitney test, receiver operator characteristic, stepwise logistic regression and least squares support vector machines (LSSVM).Plasma levels of IL-6, IL-8 and CA-125 were increased in all women with endometriosis and in those with minimal-mild endometriosis, compared with controls. In women with moderate-severe endometriosis, plasma levels of IL-6, IL-8 and CA-125, but also of hsCRP, were significantly higher than in controls. Using stepwise logistic regression, moderate-severe endometriosis was diagnosed with a sensitivity of 100% (specificity 84%) and minimal-mild endometriosis was detected with a sensitivity of 87% (specificity 71%) during the secretory phase. Using LSSVM analysis, minimal-mild endometriosis was diagnosed with a sensitivity of 94% (specificity 61%) during the secretory phase and with a sensitivity of 92% (specificity 63%) during the menstrual phase.Advanced statistical analysis of a panel of six selected plasma biomarkers on samples obtained during the secretory phase or during menstruation allows the diagnosis of both minimal-mild and moderate-severe endometriosis with high sensitivity and clinically acceptable specificity.

The 0° and 180°, as well as the 90° differential cross sections for the 2 H(γ, p)n reaction have been measured at lab photon energies between 7 and 19 MeV. Special attention was paid to the accuracy, in particular by measuring the forward Compton electron yield. For the extreme angles, the statistical error on our results amounts to 4–5% (0°) and 7–8% (180°), respectively, while the systematic uncertainty is at most 3%. The data confirm the existence of a minimum in the forward cross section and indicate beyond any doubt that the fore/aft ratio is larger than unity. Comparison shows reasonable agreement with the results from recent “conventional” theoretical approaches, including meson exchange and relativistic corrections, although the description of the c -coefficient, appearing in the Partovi expansion of the differential cross section, remains unsatisfactory. A possible source for this discrepancy could be the inadequate description of the El and/or the E2 transition operator.

The forward2H(γ,p)n cross section was measured at 7.2 and 8.5 MeV photon energy. The new absolute values confirm the theoretically predicted presence of a minimum in this cross section. A discrimination is made between the results from various theoretical descriptions.

We introduce a model of mutually attracting agents in an arbitrary network, for which the long term behavior results in the emergence of several clusters. The cluster structure is independent of the initial condition and is characterized by a set of inequalities in the parameters of the model. With varying coupling strength, transitions between different cluster structures may take place. We illustrate the relation with the Kuramoto model on interconnected oscillators and we discuss an application on opinion formation.

Spectra of protons and deuterons emitted in the photodisintegration of $^{27}\mathrm{Al}$ and $^{\mathrm{nat}}\mathrm{Ca}$ have been measured with the tagged photon technique. The experimental data are compared to the results of calculations using the hybrid model for pre-equilibrium reactions. For the first time it is possible to determine the relevant initial doorway configuration, i.e., a 2p-1h doorway, appropriate for quasideuteron absorption.

In breast cancer, in vitro as well as in vivo experiments have shown an inverse relationship between HER-2 and steroid hormone receptors. It is unknown whether circulating estrogens affect HER-2 expression. We hypothesize that the postmenopausal body mass index (BMI) as a surrogate marker for bio-available estrogens, is inversely associated with HER-2 over-expression. A total of 535 women over age 50 or with known postmenopausal status, with a unilateral, not previously treated, operable breast cancer were evaluated the evening prior to surgery for body weight, height, abdominal and hip circumference over a 3 years period. Waist-to-hip ratio (WHR) and BMI were calculated. HER-2, estrogen receptor and progesterone receptor staining was done by immunohistochemistry. All tumours with DAKO 2+ staining were submitted for HER-2 detection by FISH analysis. HER-2 was defined as positive if DAKO 3+ or FISH positive. We assessed the frequency of HER-2 positivity in each of 6 quantiles for all parameters of body composition and tested for a trend in HER-2 expression across the 6 quantiles. Furthermore, we investigated whether BMI contributed, together with other known predictors for HER-2, in a standard multivariate logistic regression model that predicts HER-2 over-expression. There is a decrease in HER-2 over-expression per increasing quantile of BMI. In a multivariate model—including both steroid receptors—BMI remains an independent predictor for HER-2 over-expression. In women over age 50 or with known postmenopausal status with an operable breast cancer, there is an inverse association between BMI and HER-2 over-expression.

The M@CBETH (microarray classification bench-marking tool on host server) web service, available at http://www.esat.kuleuven.be/MACBETH/, offers a simple tool for making optimal two-class predictions in a clinical setting. This web service compares different classifiers and selects the best in terms of randomized test set performances. The M@CBETH website offers two services: benchmarking and prediction. Benchmarking involves selection and training of an optimal model based on a benchmarking dataset. This model is stored for immediate or later use on prospective data. The prediction service offers a way for later evaluation of prospective data by reusing an existing optimal prediction model, which is useful for classifying new unseen patients. Nine different classification methods are considered. Application of the M@CBETH benchmarking service on two binary classification problems in ovarian cancer confirms that it is important to select and train an optimal model for each microarray dataset.

Objectives To determine whether three-dimensional (3D) ultrasound including power Doppler examination of the cervix is useful for predicting time to spontaneous onset of labor or time to delivery in prolonged pregnancy. Methods A prospective study was conducted in 60 women who went into spontaneous labor. All underwent transvaginal 3D power Doppler ultrasound examination of the cervix immediately before a prolonged-pregnancy cbeck-up at >= 41 + 5 gestational weeks. Univariate and multivariate logistic regression analysis was used to determine which of the following variables predicted spontaneous onset of labor > 24 h and > 48 h and vaginal delivery > 48 h and > 60 h: length, anteroposterior (AP) diameter and width of the cervix and of any cervical funneling; cervical volume (cm(3)); vascularization index (VI); flow index (FI); vascularization flow index (VEI); parity; and Bishop score. Multivariate logistic regression analysis was carried out both with and without Bishop score as a predictive variable. Receiver-operating characteristics (ROC) curves were used to describe the diagnostic performance of the tests. Results The areas under the ROC curves for Bishop score, cervical length, and logistic regression models did not differ significantly (areas ranging from 0.72 to 0.82). If Bishop score was not included in the logistic regression model, cervical length, VI and FI independently predicted delivery > 48 h, the likelihood increasing with increasing cervical length, decreasing VI and increasing FI. Conclusions In prolonged pregnancy cervical vascularization as estimated by 3D power Doppler ultrasound is related to time to delivery > 48 h, but the likelihood of delivery > 48 h can be predicted equally well using Bishop score alone or sonograpbic cervical length alone Copyright (c) 2006 ISUOG. Published by John Wiley & Sons, Ltd. (Less)

Objectives Preoperative knowledge of the depth of myometrial infiltration is important in patients with endometrial carcinoma. This study aimed at assessing the value of histopathological parameters obtained from an endometrial biopsy (Pipelle® de Cornier; results available preoperatively) and ultrasound measurements obtained after transvaginal sonography with color Doppler imaging in the preoperative prediction of the depth of myometrial invasion, as determined by the final histopathological examination of the hysterectomy specimen (the gold standard). Methods We first collected ultrasound and histopathological data from 97 consecutive women with endometrial carcinoma and divided them into two groups according to surgical stage (Stages Ia and Ib vs. Stages Ic and higher). The areas (AUC) under the receiver–operating characteristics curves of the subjective assessment of depth of invasion by an experienced gynecologist and of the individual ultrasound parameters were calculated. Subsequently, we used these variables to train a logistic regression model and least squares support vector machines (LS-SVM) with linear and RBF (radial basis function) kernels. Finally, these models were validated prospectively on data from 76 new patients in order to make a preoperative prediction of the depth of invasion. Results Of all ultrasound parameters, the ratio of the endometrial and uterine volumes had the largest AUC (78%), while that of the subjective assessment was 79%. The AUCs of the blood flow indices were low (range, 51–64%). Stepwise logistic regression selected the degree of differentiation, the number of fibroids, the endometrial thickness and the volume of the tumor. Compared with the AUC of the subjective assessment (72%), prospective evaluation of the mathematical models resulted in a higher AUC for the LS-SVM model with an RBF kernel (77%), but this difference was not significant. Conclusions Single morphological parameters do not improve the predictive power when compared with the subjective assessment of depth of myometrial invasion of endometrial cancer, and blood flow indices do not contribute to the prediction of stage. In this study an LS-SVM model with an RBF kernel gave the best prediction; while this might be more reliable than subjective assessment, confirmation by larger prospective studies is required. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

BACKGROUND: As women present at earlier gestations to early pregnancy units (EPUs), the number of women diagnosed with a pregnancy of unknown location (PUL) increases. Some of these women will have an ectopic pregnancy (EP), and it is this group in the PUL population that poses the greatest concern. The aim of this study was to develop Bayesian networks to predict EPs in the PUL population. METHODS: Data were gathered in a single EPU from all women with a PUL. This data set was divided into a model-building (599 women with 44 EPs) and a validation (257 women with 22 EPs) data set and consisted of the following variables: vaginal bleeding, fluid in the pouch of Douglas, midline echo, lower abdominal pain, age, endometrial thickness, gestation days, the ratio of HCG at 48 and 0 h, progesterone levels (0 and 48 h) and the clinical outcome of the PUL. We developed Bayesian networks with expert information using this data set to predict EPs. RESULTS: The best Bayesian network used the gestational age, HCG ratio and the progesterone level at 48 h and had an area under the receiver operator characteristic curve (AUC) of 0.88 for predicting EPs when tested prospectively. CONCLUSIONS: Discrete-valued Bayesian networks are more complex to build than, for example, logistic regression. Nevertheless, we have demonstrated that such models can be used to predict EPs in a PUL population. Prospective interventional multicentre studies are needed to validate the use of such models in clinical practice.

We investigated whether prognostic information is reflected in the expression patterns of ovarian carcinoma samples. RNA obtained from seven FIGO stage I without recurrence, seven platin-sensitive advanced-stage (III or IV), and six platin-resistant advanced-stage ovarian tumors was hybridized on a complementary DNA microarray with 21,372 spotted clones. The results revealed that a considerable number of genes exhibit nonaccidental differential expression between the different tumor classes. Principal component analysis reflected the differences between the three tumor classes and their order of transition. Using a leave-one-out approach together with least squares support vector machines, we obtained an estimated classification test accuracy of 100% for the distinction between stage I and advanced-stage disease and 76.92% for the distinction between platin-resistant versus platin-sensitive disease in FIGO stage III/IV. These results indicate that gene expression patterns could be useful in clinical management of ovarian cancer.

Objectives To determine the ability of Bishop score and sonographic cervical length to predict time to spontaneous onset of labor and time to delivery in prolonged pregnancy. Methods Ninety-seven women underwent transvaginal ultrasound examination and palpation of the cervix at 291-296 days' gestation according to ultrasound fetometry at 12-20 weeks' gestation. Sonographic cervical length and Bishop score were recorded. Multivariate logistic regression analysis was used to determine which variables were independent predictors of the onset of labor/delivery 24 h, 48 h, and 96 h. Receiver-operating characteristics (ROC) curves were drawn to assess diagnostic performance. Results In nulliparous women (n = 45), both Bishop score and sonographic cervical length predicted the onset of labor/delivery 24 h and 48 h (area under ROC curve for the onset of labor 24 h 0.79 vs. 0.80, P = 0.94; for delivery 24 h 0.81 vs. 0.85, P = 0.64; for the onset of labor 48 h 0.73 vs. 0.74, P = 0.90; for delivery 48 h 0.77 vs. 0.71, P = 0.50). Only Bishop score discriminated between nulliparous women who went into labor/delivered 96 h or > 96 h. A logistic regression model including Bishop score and cervical length was superior to Bishop score alone in predicting delivery 24 h (area under ROC curve 0.93 vs. 0.81, P = 0.03) and superior to Bishop score alone and cervical length alone in predicting the onset of labor 24 h (area under ROC curve 0.90 vs. 0.79, P = 0.06; and 0.90 vs. 0.80, P = 0.06). In parous women (n = 52), Bishop score and sonographic cervical length predicted the onset of labor/delivery 24 h (area under ROC curve for the onset of labor 0.75 vs. 0.69, P = 0.49; for delivery 0.74 vs. 0.70, P = 0.62), but only Bishop score discriminated between women who went into labor/delivered 48 h and > 48 h. Three parous women had not gone into labor and six had not given birth at 96 h. In parous women logistic regression models including both Bishop score and cervical length did not substantially improve prediction of the time to onset of labor/delivery. Conclusions In prolonged pregnancy Bishop score and sonographic cervical length have a similar ability to predict the time to the onset of labor and delivery. In nulliparous women the use of logistic regression models including Bishop score and cervical length is likely to offer better prediction of the onset of labor/delivery 24 h than the use of the Bishop score alone.

Various serum human chorionic gonadotropin (hCG) discriminatory zones are currently used for evaluating the likelihood of an ectopic pregnancy in women classified as having a pregnancy of unknown location (PUL) following a transvaginal ultrasound examination. We evaluated the diagnostic accuracy of discriminatory zones for serum hCG levels of1000 IU/L, 1500 IU/L and 2000 IU/L for the detection of ectopic pregnancy in such women.This was a prospective observational study of women who were assessed in a specialized transvaginal scanning unit. All women with a PUL had serum hCG measured at presentation. Expectant management of PULs was adopted. These women were followed up with transvaginal ultrasound, monitoring of serum hormone levels and laparoscopy until a final diagnosis was established: a failing PUL, an intrauterine pregnancy (IUP), an ectopic pregnancy or a persisting PUL. The persisting PULs probably represented ectopic pregnancies which had been missed on ultrasound and these were incorporated into the ectopic pregnancy group. Three different discriminatory zones (1000 IU/L, 1500 IU/L and 2000 IU/L) were evaluated for predicting ectopic pregnancy in this PUL population.A total of 5544 consecutive women presented to the early pregnancy unit between 25 June 2001 and 14 April 2003. Of these, 569 (10.3%) women were classified as having a PUL, 42 of which were lost to follow up. Of the 527 (9.5%) cases with PUL analyzed, there were 300 (56.9%) failing PULs, 181 (34.3%) IUPs and 46 (8.7%) ectopic pregnancies. Overall, 74.6% were symptomatic and 25.4% were asymptomatic (P = 8.825E-07). The sensitivity and specificity of an hCG level of1000 IU/L to detect ectopic pregnancy were 21.7% (10/46) and 87.3% (420/481), respectively; for an hCG level of1500 IU/L these values were 15.2% (7/46) and 93.4% (449/481), respectively, and for an hCG level of2000 IU/L they were 10.9% (5/46) and 95.2% (458/481), respectively.Varying the discriminatory zone does not significantly improve the detection of ectopic pregnancy in a PUL population. A single measurement of serum hCG is not only potentially falsely reassuring but also unhelpful in excluding the presence of an ectopic pregnancy.

To describe the gray-scale sonographic and color Doppler imaging features of the most common histopathological subtypes of borderline ovarian tumors.We analyzed retrospectively the preoperative transvaginal sonographic reports of patients with a histological diagnosis of borderline ovarian tumor. All patients were scanned consecutively by two of the investigators using transabdominal and transvaginal gray-scale imaging to assess the morphology and color Doppler to obtain indices of the blood flow. Sonographic findings were compared to histopathological data.A total of 113 consecutive cases were reviewed from two referral centers for gynecological oncology. At histological examination 50 tumors (44%) were classified as being serous borderline ovarian tumors (SBOT), 61 (54%) were mucinous borderline ovarian tumors (MBOT) (42 intestinal type and 19 endocervical type), and two patients (2%) presented with borderline endometrioid tumors. SBOTs and endocervical-type MBOTs had very similar sonographic features and a smaller diameter, fewer locules (usually unilocular-solid lesions) and a higher color score than intestinal-type MBOTs. Intestinal-type MBOTs were characterized by a significantly higher percentage of lesions with10 locules when compared with the endocervical-type MBOTs.Intestinal-type MBOTs have different sonographic features from other common borderline ovarian tumors.

To determine if power Doppler ultrasound examination of the endometrium can contribute to a correct diagnosis of endometrial malignancy in women with postmenopausal bleeding and endometriumor = 5 mm.Eighty-three women with postmenopausal bleeding and endometriumor = 5 mm underwent gray-scale and power Doppler ultrasound examination using predetermined, standardized settings. Suspicion of endometrial malignancy at gray-scale ultrasound examination (endometrial morphology) was noted, and the color content of the endometrium at power Doppler examination was estimated subjectively (endometrial color score). Computer analysis of the most vascularized area of the endometrium was done off-line in a standardized manner. Stepwise multivariate logistic regression analysis was carried out to determine which subjective and objective ultrasound and power Doppler variables satisfied the criteria to be included in a model to calculate the probability of endometrial malignancy.Endometrial thickness, vascularity index (vascularized area/endometrial area), and use of hormone replacement therapy (HRT) satisfied the criteria to be included in the model used to calculate the 'objective probability of endometrial malignancy'. Endometrial morphology, endometrial color score and HRT use satisfied the criteria to be included in the model to calculate the 'subjective probability of malignancy'. Endometrial thicknessor = 10.5 mm had a sensitivity with regard to endometrial cancer of 0.88 and a specificity of 0.61. At a fixed sensitivity of 0.88, the specificity of the 'objective probability of malignancy' (0.81) was superior to all other ultrasound and power Doppler variables (P = 0.001-0.02). The 'objective probability of malignancy' detected more malignancies at endometrium 5-15 mm than endometrial morphology (5/7 vs. 1/7, i.e. 0.71 vs. 0.14; P = 0.125) with a similar specificity (49/57 vs. 51/57, i.e. 0.86 vs. 0.89).Power Doppler ultrasound can contribute to a correct diagnosis of endometrial malignancy, especially if the endometrium measures 5-15 mm. The use of regression models including power Doppler results to estimate the risk of endometrial cancer deserves further development.

Due to the increasing contribution of the neutron dose to the total dose of the BELGONUCLEAIRE personnel and the introduction of the ICRP 60 recommendations,1 the use of a more reliable personal neutron dosemeter has become even more important. A Canadian2 dosimeter manufactured by Bubble Technology Industries seemed to be a very interesting alternative to the albedo dosimeter used in the past. An extensive investigation program was carried out at BELGONUCLEAIRE to determine the effectiveness of the new dosimeter in the fuel fabrication plant environment. A series of tests were conducted to get a better understanding of this type of dosemeter.

The New CDC-definitions for surveillance of surgical site infections (1992) take into account 3 classes of surgical site infections (SSI): superficial and deep incisional SSI, and organ/space SSI. The most important host-related risk factors for development of SSI are advanced age, morbid obesity, disease severity, an ASA score > 2, prolonged preoperative hospital stay, and infection at distal sites. Microbial contamination of the surgical site occurs mainly during the surgical intervention. Although exogenous contamination may be of concern, especially in clean operations, most surgical site infections are caused by microorganisms of the patient's own commensal flora. SSI rates vary according to the type and duration of the surgical procedure and the skill of the surgeon. Proper surgical technique is the most important factor in the prevention of SSI. Modification of host risk factors should be attempted whenever possible. In addition, adequate protocols for antimicrobial prophylaxis with antibiotics should be followed. Surveillance of surgical site infections is probably beneficial for SSI prevention.

The total deuteron photodisintegration cross section has been determined in an alternative way, based on the absolute measurement of the 90{degree} cross section and, to a lesser extent, the 0{degree} and 180{degree} cross sections. The accuracy of the deduced total cross sections amounts to 3%, including systematic errors. The agreement of our data with the results from recent theoretical calculations is very good.