Real-time feedback control of the impurity emission front in tokamak divertor plasmas.

In magnetic confinement thermonuclear fusion the exhaust of heat and particles from the core remains a major challenge. Heat and particles leaving the core are transported via open magnetic field lines to a region of the reactor wall, called the divertor. Unabated, the heat and particle fluxes may become intolerable and damage the divertor. Controlled 'plasma detachment', a regime characterized by both a large reduction in plasma pressure and temperature at the divertor target, is required to reduce fluxes onto the divertor. Here we report a systematic approach towards achieving this critical need through feedback control of impurity emission front locations and its experimental demonstration. Our approach comprises a combination of real-time plasma diagnostic utilization, dynamic characterization of the plasma in proximity to the divertor, and efficient, reliable offline feedback controller design.

Effect of gender difference on platelet reactivity.

BACKGROUND: Previous studies have suggested that women do not accrue equal therapeutic benefit from antiplatelet medication as compared with men. The physiological mechanism and clinical implications behind this gender disparity have yet to be established. METHODS: On-treatment platelet reactivity was determined in 717 men and 234 women on dual antiplatelet therapy, undergoing elective coronary stent implantation. Platelet function testing was performed using arachidonic acid and adenosine diphosphate-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 and Aspirin assays. Also the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke was evaluated. RESULTS: Women had higher baseline platelet counts than men. Women exhibited a higher magnitude of on-aspirin platelet reactivity using LTA, but not using the VerifyNow Aspirin assay. The magnitude of on-clopidogrel platelet reactivity was significantly higher in women as compared with men with both tests used. The cut-off value to identify patients at risk as well as the incidence of clinical endpoints was similar between women and men (16/234[6.8%] vs. 62/717[8.6%], p = 0.38). CONCLUSION: Although the magnitude of platelet reactivity was higher in women, the absolute difference between genders was small and both the cut-off value to identify patients at risk and the incidence of the composite endpoint were similar between genders. Thus, it is unlikely that the difference in platelet reactivity accounts for a worse prognosis in women.

Metastatic oligodendroglioma: a case report and incidence in The Netherlands.

Oligodendroglioma is a tumor of the central nervous system which rarely metastasizes. The diagnosis of oligodendroglioma is based on histomorphology with limited use of immunohistochemistry. However, recently a specific 1p/19q codeletion has been found which can be demonstrated by in situ hybridization. We report a case of a 58-years-old man with a 31-months history of oligodendroglioma presenting with fatigue and anemia. A bone marrow biopsy demonstrated massive localization of oligodendroglioma which was confirmed by in situ hybridization for the 1p/19q deletion. In addition we studied data from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands and found an incidence of approximately 2 in 1,000 for metastasis of oligodendroglioma outside the central nervous system.

Coverage and yield of entry and follow-up screening for tuberculosis among new immigrants.

The aim of the present study was to determine the effectiveness of entry screening for tuberculosis and biannual follow-up screening among new immigrants in The Netherlands. To achieve this, the present authors analysed screening, prevalence and incidence data of 68,122 immigrants, who were followed for 29 months. Patients diagnosed within 5 months and 6-29 months after entry screening were considered to be detected at entry and during the follow-up period, respectively. Coverage of the second to fifth screening rounds was 59, 46, 36 and 34%, respectively. Yield of entry screening was 119 per 100,000 individuals, and prevalence at entry was 131 per 100,000. Average yield of follow-up screening was highest among immigrants with abnormalities on chest radiography (CXR) at entry (902 per 100,000 individuals). When excluding these, yield of follow-up screening was 9, 37 and 97 per 100,000 screenings for immigrants from countries with tuberculosis incidences of <100, 100-200 and >200 per 100,000, respectively. The incidence during follow-up in individuals with a normal CXR was 11, 58 and 145 per 100,000 person-yrs follow-up in these groups. The proportion of cases detected through screening declined per screening round from 91 to 31%. Yield of entry screening was high. Overall coverage and yield of follow-up screening was low. Follow-up screening of immigrants with a normal chest radiograph from countries with an incidence of <200 per 100,000 individuals was therefore discontinued.

[Dose reduction of conventional antipsychotics: does it reduce tardive dyskinesia?]. / Dosisreductie van klassieke antipsychotica: gunstig voor tardieve dyskinesie?

The first step in the treatment of tardive dyskinesia is to reduce the dose of antipsychotics. The view sometimes expressed in general practice is that, initially, dose reduction exacerbates tardive dyskinesia, which is an effect that can be explained on theoretical grounds. However, it is apparent from published scientific research that dose reduction of conventional antipsychotics tends to improve tardive dyskinesia rather than exacerbate it.

CD13/Aminopeptidase N overexpression by basic fibroblast growth factor mediates enhanced invasiveness of 1F6 human melanoma cells.

CD13/Aminopeptidase N (CD13) is known to play an important role in tumour cell invasion. We examined whether basic fibroblast growth factor (bFGF) is involved in the regulation of CD13 expression in human melanoma cells. 1F6 human melanoma cells were stably transfected with constructs encoding either the 18 kDa (18 kD) or all (ALL) bFGF isoform proteins. We observed highly increased CD13 mRNA and protein expression in the 1F6 clones regardless of the overexpression of either the 18 kD or all isoform proteins. Neutral aminopeptidase activity was increased five-fold and could be inhibited by bestatin and the CD13-neutralising antibody WM15. The enhanced invasion through Matrigel, but not migration in a wound assay, was efficiently abrogated by both bestatin and WM15. Upregulation of CD13 expression was the result of increased epithelial and myeloid promoter activity up to 4.5-fold in 1F6-18 kD and 1F6-ALL clones. Interestingly, in a panel of human melanoma cell lines, a significant correlation (r(2)=0.883, P<0.05) between bFGF and CD13 mRNA and protein expression was detected. High bFGF and CD13 expression were clearly related with an aggressive phenotype. Taken together, our data indicate that high bFGF expression upregulates CD13 expression in human melanoma cells by activating both the myeloid and the epithelial CD13 promoter. In addition, we show that high bFGF and CD13 expression results in enhanced invasive capacity and metastatic behaviour of human melanoma cells.

Differential prognostic impact of hypoxia induced and diffuse HIF-1alpha expression in invasive breast cancer.

BACKGROUND: Intratumorous hypoxia triggers a broad cellular response mediated by the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1alpha concentrations increase during breast carcinogenesis, and are associated with poor prognosis. An earlier study noted two HIF-1alpha overexpression patterns: diffuse scattered throughout the tissue and confined to perinecrotic cells. AIMS: To investigate the prognostic impact of these different HIF-1alpha overexpression patterns in relation to its downstream effectors carbonic anhydrase (CA) IX and glucose transporter 1 (GLUT-1). METHODS: HIF-1alpha, CA IX, and GLUT-1 expression was studied by immunohistochemistry, including double staining for CA IX and HIF-1alpha. Clinical data included disease free survival, lymph node status, and tumour size. RESULTS: HIF-1alpha overexpression (44% of cases) had a perinecrotic (13.5%) or diffuse staining pattern (30.5%). CA IX expression was detectable in 12.5% of breast cancers, whereas GLUT-1 expression was seen in 29%, with both showing perinecrotic membrane staining. Perinecrotic HIF-1alpha overexpression was highly associated with CA IX and GLUT-1 overexpression, and double staining for HIF-1alpha and CA IX showed strong expression in the same cells. Diffusely overexpressed HIF-1alpha was not associated with CA IX or GLUT-1 expression. Patients with diffuse HIF-1alpha staining had a significantly better prognosis than patients with perinecrotically overexpressed HIF-1alpha. CONCLUSIONS: Different regulation pathways of HIF-1alpha overexpression exist in breast cancer: (1) hypoxia induced, perinecrotic HIF-1alpha overexpression with strong expression of hypoxia associated genes (CA IX and GLUT-1), which is associated with a poor prognosis; and (2) diffuse HIF-1alpha overexpression lacking major hypoxia associated downstream effects, resulting in a more favourable prognosis.

CD28/CTLA4 double deficient mice demonstrate crucial role for B7 co-stimulation in the induction of allergic lower airways disease.

BACKGROUND: The existence of a third B7-1/B7-2 receptor was postulated in a recent study using a novel mouse strain lacking both CD28 and CTLA4 (CD28/CTLA4-/-). OBJECTIVE: In the present study, it was investigated if T cell co-stimulation via the putative B7-1/B7-2 receptor plays a role in the induction of Th2-mediated asthma manifestations in mice. METHODS: BALB/c wild-type, CD28/CTLA4-/- and B7-1/B7-2-/- mice were sensitized and aerosol challenged with ovalbumin (OVA). RESULTS: At 24 h after the last aerosol, wild-type mice showed airway hyper-responsiveness in vivo and up-regulated levels of serum OVA-specific IgE compared with the situation shortly before OVA challenge. In addition, eosinophil numbers and IL-5 levels in the broncho-alveolar lavage fluid and Th2 cytokine production by lung cells upon OVA re-stimulation in vitro were observed. In agreement with an earlier study, we failed to induce any of the asthma manifestations in B7-1/B7-2-/- mice. Importantly, also CD28/CTLA4-/- mice showed no asthma manifestations upon OVA sensitization and challenge. CONCLUSION: These data clearly demonstrate that T cell co-stimulation via the putative B7-1/B7-2 receptor appears to have no role in the induction of Th2-mediated asthma manifestations in this murine model and, conversely, that CD28 signalling is crucial.

The Saccharomyces cerevisiae CWH8 gene is required for full levels of dolichol-linked oligosaccharides in the endoplasmic reticulum and for efficient N-glycosylation.

The Saccharomyces cerevisiae mutant cwh8 was previously found to have an anomalous cell wall. Here we show that the cwh8 mutant has an N -glycosylation defect. We found that cwh8 cells were resistant to vanadate and sensitive to hygromycin B, and produced glycoforms of invertase and carboxypeptidase Y with a reduced number of N -chains. We have cloned the CWH8 gene. We found that it was nonessential and encoded a putative transmembrane protein of 239 amino acids. Comparison of the in vitro oligosaccharyl transferase activities of membrane preparations from wild type or cwh8 Delta cells revealed no differences in enzyme kinetic properties indicating that the oligosaccharyl transferase complex of mutant cells was not affected. cwh8 Delta cells also produced normal dolichols and dolichol-linked oligosaccharide intermediates including the full-length form Glc3Man9GlcNAc2. The level of dolichol-linked oligosaccharides in cwh8 Delta cells was, however, reduced to about 20% of the wild type. We propose that inefficient N -glycosylation of secretory proteins in cwh8 Delta cells is caused by an insufficient supply of dolichol-linked oligosaccharide substrate.

[The ear thermometer; not a good replacement for the rectal thermometer]. / De oorthermometer: geen goede vervanger van de rectale thermometer.

OBJECTIVE: To compare the measurements of body temperature with the tympanic infrared thermometer and the digital rectal thermometer. DESIGN: Prospective, comparative. SETTING: Beatrix Hospital, Gorinchem, the Netherlands. PATIENTS AND METHODS: A total of 2057 almost simultaneous measurements of rectal and tympanic temperature were performed in 164 patients in 9 different wards. RESULTS: The mean difference between the two methods was 0.45 degree C with a standard deviation of 0.57 degree C. The tympanic temperature was lower than the rectal temperature. The differences ranged from -1.5 to 3.6 degrees C. The correlation coefficient was 0.69. If a rectal temperature > 37.8 degrees C was applied as the criterion of fever, the diagnosis was not made in 175/291 measuring moments (60%) with the tympanic thermometer. If a tympanic temperature > 37.8 degrees C was applied as the criterion of fever, the rectal thermometer failed to show fever in 16/132 measuring moments (12%). CONCLUSION: The low sensitivity of the tympanic measurement to establish fever renders the tympanic infrared thermometer unsuitable for use as a fever thermometer.

Married women's economic dependency in The Netherlands, 1979-1991.

The present paper offers a replication of an analysis by Sørensen and McLanahan (1987) of 1940-1980 USA data on trends in married women's economic dependency, this time using Dutch income data for 1979-1991. The results show that in the Netherlands, as opposed to the USA, a vast majority of the wives are still completely or strongly dependent on their husband's income. Yet, also Dutch wives' economic dependency is decreasing at a significant rate. Despite clear life course differences that yet seem to persist, we observe declining levels of dependency within each age group. This declining trend seems to reflect mostly changes in married women's employment status over time. An implication of the reported trend, however, is that it becomes increasingly important to study the influence of the social position of both partners.

Pulmonary oedema, pneumonia and mortality in submersion victims; a retrospective study in 125 patients.

OBJECTIVE: The identification of risk factors contributing to the development of pulmonary oedema, pneumonia and late mortality in submersion victims. DESIGN: A retrospective study of 125 submersion victims. SETTING: The medical intensive care unit in a university hospital. METHODS: Baseline examination on admission consisted of history, physical examination, arterial blood gas analysis and a chest radiograph. Patients were then classified into four groups: class I, baseline examination negative; class II, baseline examination positive, but mechanical ventilation not needed on admission; class III, mechanical ventilation required on admission; class IV, patients suffering from cardiopulmonary arrest. All patients who were not successfully resuscitated or who had expired within 24 h after admission were excluded for determination of the risk of pulmonary oedema and pneumonia. RESULTS: Class I patients did not develop pulmonary complications; neither pulmonary oedema nor pneumonia occurred in this group. In the remaining classes the incidence of pulmonary oedema was 72% and that of pneumonia, 14.7%. Stepwise logistic regression showed that pulmonary oedema was related to the type of water (seawater, ditch water, swimming pool) victims were submerged in and to the neurological state both at the time of rescue and on admission. The development of pneumonia was related to the use of mechanical ventilation (the risk was 52%). Pneumonia was not related to neurological state at the time of rescue or on admission, to body temperature on admission, to the prophylactic administration of antibiotics or to the use of corticosteroids. Mortality was high in class IV patients, but low in all other patients. Early mortality was 18.4% while late mortality was 5.6%. CONCLUSIONS: There is no need to hospitalise submersion victims when there are no signs or symptoms of aspiration upon arrival in the emergency room. All other patients should be admitted to an intensive care unit. The risk of pneumonia is high when mechanical ventilation is necessary. Mortality is high in patients with circulatory arrest on admission, but low in all other patients.

Global water crisis: the major issue of the 21st century, a growing and explosive problem.

PIP: The authors explore what is considered to be the emerging issue of the 21st century, shortages of water. It is expected that the Netherlands, which is entirely dependent on water from other countries, will be in an extremely vulnerable position. The quantity of fresh water is limited. Contamination of water reduces water quality and availability. Many World Bank projects focus on management of the water supply for sanitation, irrigation, hydroelectric power, and construction of dikes in order to prevent flooding. The World Bank concludes that everyone worldwide must acknowledge that fresh water is a scarce natural resource. The Action Plan, Agenda 21, of the UN Rio Conference emphasized the importance of the widespread shortage, gradual destruction, and increased pollution of fresh water reserves. The four major world problems with fresh water are 1) shortages of renewable supplies, 2) unequal distribution of supplies, 3) problems of water quality and health, and 4) disastrous effects of unrestrained construction of dams and reservoirs. Only 2.5% of the total amount of water on earth is fresh water, of which 69.4% is in the form of ice, snow, or permafrost and most of the remainder is ground water. Fresh water in lakes and rivers is only about 1% of fresh water available on earth. Most of the precipitation that falls on land every year is lost through evaporation. 45,000 sq. km is the absolute maximum available annually. Distribution of water among industry, agriculture, and households varies by country. Arid regions constitute about 33% of Europe, 60% of Asia, 85% of Africa, and most of Australia and western North America. 14% of countries are at or under the poverty line of water availability, 37% have dangerously dry conditions, 14% have average levels, and 35% have ample supplies. Examples of water management are given for the Amazon River, the Euphrates and Tigris, the Aral Sea, and the Rhine River Basin. It is estimated that the world supply of fresh water would meet the needs of 4.5-9.0 billion people.^ieng

Glucosylation of chimeric proteins in the cell wall of Saccharomyces cerevisiae.

Extension of a reporter protein with the carboxyterminal thirty amino acids of the cell wall mannoprotein alpha-agglutinin of Saccharomyces cerevisiae resulted in incorporation of the chimeric protein in the cell wall. By Western analysis it was shown that the incorporated protein contained beta-1,6-glucan similar to endogenous cell wall proteins, whereas excreted reporter protein was not glucosylated. This suggests that beta-1,6-glucan is involved in anchoring mannoproteins in the cell wall.

Inactivation of human immunodeficiency virus by gamma radiation and its effect on plasma and coagulation factors.

The inactivation of HIV by gamma-radiation was studied in frozen and liquid plasma; a reduction of the virus titer of 5 to 6 logs was achieved at doses of 5 to 10 Mrad at -80 degrees C and 2.5 Mrad at 15 degrees C. The effect of irradiation on the biologic activity of a number of coagulation factors in plasma and in lyophilized concentrates of factor VIII (FVIII) and prothrombin complex was examined. A recovery of 85 percent of the biologic activity of therapeutic components present in frozen plasma and in lyophilized coagulation factor concentrates was reached at radiation doses as low as 1.5 and 0.5 Mrad, respectively. As derived from the first-order radiation inactivation curves, the radiosensitive target size of HIV was estimated to be 1 to 3 MDa; the target size of FVIII was estimated to be 130 to 160 kDa. Gamma radiation must be disregarded as a method for the sterilization of plasma and plasma-derived products, because of the low reduction of virus infectivity at radiation doses that still give acceptable recovery of biologic activity of plasma components.

Submersion in The Netherlands: prognostic indicators and results of resuscitation.

STUDY OBJECTIVES: To analyze prognostic indicators and the outcome of resuscitation in submersion victims (drowning and near drowning). DESIGN: Retrospective study. SETTING: Intensive and Respiratory Care Unit. Between January 1, 1979, and December 31, 1985, 87 submersion victims were admitted. The files of 83 victims were available for statistical analysis. There were 66 male victims and 17 female victims; the average age was 31.4 +/- 25.8 years. There were ten salt water and 73 fresh water submersions. MEASUREMENTS AND MAIN RESULTS: Predictors for better survival potentials were a young age, submersion of less than ten minutes, no signs of aspiration, and a central body temperature of less than 35 C at admission. We did not detect factors that accelerated a decrease in core body temperature at admission and assume that lethal hypoxia had preceded protective hypothermia in our submersion victims. The Orlowski score had a predictive value but at the same time we found nonindependent indicators in this score. Neurologic outcome in our patients, who were not treated according to a brain protection protocol, was not worse than the outcome published by authors who have used such a protocol. Thirty-three percent of the victims with a cardioventilatory arrest (15) and all victims with a ventilatory arrest (11) survived resuscitation and were discharged. Five nonarrest victims died due to late complications. CONCLUSION: This study shows that no indicator at the rescue site and in the hospital is absolutely reliable with respect to death or survival.

Tension subcutaneous emphysema. A case report.

A case is presented of severe barotrauma due to thoracoscopy with multiple lung biopsies and consecutive mechanical ventilation for pneumocystis carinii pneumonia. When tension subcutaneous emphysema developed, circulatory collapse occurred. Relief of pressure by a subcutaneous drain reversed the circulatory state.