59 research outputs found
Evaluating performance of multivariable vibration isolators : a frequency domain identification approach applied to an industrial AVIS:A frequency domain identification approach applied to an industrial AVIS
Vibration isolation is essential for industrial high-precision systems in suppressing the influence of external disturbances. The aim of this paper is to develop an identification method to estimate the transmissibility matrix for such systems. The transmissibility matrix is a key performance indicator in vibration isolation, but its identification is severely limited by the heavy weight and size of many industrial systems. Two non-parametric system identification methods based on periodic and spectral analysis are compared. It is shown that spectral analysis can benefit from random floor excitations at low frequencies and periodic shaker excitations at high frequencies. Using this method, a transmissibility matrix between 1 and 100 Hz is successfully measured on an industrial active vibration isolation system (AVIS), demonstrating that the proposed method is suitable for identification of these heavy-weight systems.</p
Evaluating performance of multivariable vibration isolators : a frequency domain identification approach applied to an industrial AVIS:A frequency domain identification approach applied to an industrial AVIS
Vibration isolation is essential for industrial high-precision systems in suppressing the influence of external disturbances. The aim of this paper is to develop an identification method to estimate the transmissibility matrix for such systems. The transmissibility matrix is a key performance indicator in vibration isolation, but its identification is severely limited by the heavy weight and size of many industrial systems. Two non-parametric system identification methods based on periodic and spectral analysis are compared. It is shown that spectral analysis can benefit from random floor excitations at low frequencies and periodic shaker excitations at high frequencies. Using this method, a transmissibility matrix between 1 and 100 Hz is successfully measured on an industrial active vibration isolation system (AVIS), demonstrating that the proposed method is suitable for identification of these heavy-weight systems.</p
Techniques of futuring: On how imagined futures become socially performative
The concept of the future is re-emerging as an urgent topic on the academic agenda. In this article, we focus on the āpolitics of the futureā: the social processes and practices that allow particular imagined futures to become socially performative. Acknowledging that the performativity of such imagined futures is well-understood, we argue that how particular visions come about and why they become performative is underexplained. Drawing on constructivist sociological theory, this article aims to fill (part of) this gap by exploring the question āhow do imagined futures become socially performativeā? In doing so, the article has three aims to (1) identify the leading socialātheoretical work on the future; (2) conceptualize the relationship of the imagination of the future with social practices and the performance of reality; (3) provide a theoretical framework explaining how images of the future become performative, using the concepts ātechniques of futuringā and ādramaturgical regimeā
Determination of Ki-67 defined growth fraction by monoclonal antibody MIB- I in formalin-fixed, paraffin-embedded prostatic cancer tissues
The applicability of MIBā1, a monoclonal antibody directed against the Kiā67 antigen, was studied in the PCā82 and LNCaP prostatic tumor models at various levels of proliferative activity. Statistically significant correlations were found in LNCaP cultures between Kiā67 and MIBā1 scores (r = 0.84, P < 0.001), and in PCā82 tumors between MIBā1 scores and paraffin tissue Kiā67 (pKiā67) (r = 0.90, P < 0.001), frozen tissue Kiā67 (fKiā67) (r = 0.86, P < 0.001), and BrdU uptake (r = 0.70, P < 0.001), respectively. pKiā67 scores were double the fKiā67 scores, which may be due to methodological differences. MIBā1 scores exceeded both the fKiā67 and pKiā67 scores. The affinity of MIBā1 for the antigen is much higher than the affinity of Kiā67, which may explain the differences. MIBā1 is a promising means of evaluating the presence of only minute amounts of the Kiā67 antigen in paraffināembedded human tumor material, especially in relatively slowly growing tumors
Influence of beta(2)-adrenoceptor gene polymorphisms on diet-induced thermogenesis
The sympathetic nervous system is involved in the control of energy metabolism and expenditure. Diet-induced thermogenesis is mediated partly by the Ć-adrenergic component of this system. The aim of the present study was to investigate the role of genetic variation in the Ć2-adrenoceptor in diet-induced thermogenesis. Data from twenty-four subjects (fourteen men and ten women; BMI 26Ā·7(SEM 0Ā·8) kg/m2; age 45Ā·2(SEM1Ā·4) years) with different polymorph-isms of the Ć2-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma concentrations of NEFA, glycerol, glucose, insulin and catecholamines were measured before and over 4 h after the meal. The AUC of energy expenditure (diet-induced thermogenesis) was not significantly different between poly-morphism groups, nor was the response of any of the other measured variables to the meal. In a multiple regression model, the only variable that explained a significant proportion (32 %) of the variation in diet-induced thermogenesis was the increase in plasma adrenaline in response to the meal (P,0Ā·05). The Ć2-adrenoceptor codon16 polymorphisms did not contribute significantly. In conclusion, an independent contribution of the codon 16 polymorphism of the Ć2-adrenoceptor gene to the variation in thermogenic response to a high-carbohydrate meal could not be demonstrated. The interindividual variation in thermo-genic response to the meal was correlated with variations in the plasma adrenaline response to the meal. Ć2-Adrenoceptor polymorphisms: Diet-induced thermogenesis: Catecholamines Energy expenditure (EE) is an important factor in body-weight regulation. Diet-induced thermogenesis (DIT) is the EE associ-ated with ingestion, absorption and storage of food and account
The predictive value of the modified early warning score for admission to the intensive care unit in patients with a hematologic malignancy ā A multicenter observational study
Objectives: The modified early warning score (MEWS) is used to detect clinical deterioration of hospitalized patients. We aimed to investigate the predictive value of MEWS and derived quick Sequential Organ Failure Assessment (qSOFA) scores for intensive care unit admission in patients with a hematologic malignancy admitted to the ward. Design: Retrospective, observational study in two Dutch university hospitals. Setting: Data from adult patients with a hematologic malignancy, admitted to the ward over a 2-year period, were extracted from electronic patient files. Main outcome measures: Intensive care admission. Results: We included 395 patients with 736 hospital admissions; 2% (n = 15) of admissions resulted in admission to the intensive care unit. A higher MEWS (OR 1.5; 95 %CI 1.3ā1.80) and qSOFA (OR 4.4; 95 %CI 2.1ā9.3) were associated with admission. Using restricted cubic splines, a rise in the probability of admission for a MEWS ā„ 6 was observed. The AUC of MEWS for predicting admission was 0.830, the AUC of qSOFA was 0.752. MEWS was indicative for intensive care unit admission two days before admission. Conclusions: MEWS was a sensitive predictor of ICU admission in patients with a hematologic malignancy, superior to qSOFA. Future studies should confirm cut-off values and identify potential additional characteristics, to further enhance identification of critically ill hemato-oncology patients. Implications for Clinical Practice: The Modified Early Warning Score (MEWS) can be used as a tool for healthcare providers to monitor clinical deterioration and predict the need for intensive care unit admission in patients with a hematologic malignancy. Yet, consistent application and potential reevaluation of current thresholds is crucial. This will enable bedside nurses to more effectively identify patients needing adjunctive care, facilitating timely interventions and improved outcome.</p
Kinetics of neuroendocrine differentiation in an androgen-dependent human prostate xenograft model
It was previously shown in the PC-295 xenograft that the number of
chromogranin A (CgA)-positive neuroendocrine (NE) cells increased after
androgen withdrawal. NE cells did not proliferate and differentiated from
G0-phase-arrested cells. Here we further characterized NE differentiation,
androgen receptor status, and apoptosis-associated Bcl-2 expression in the
PC-295 model after androgen withdrawal to assess the origin of NE cells.
PC-295 tumor volumes decreased by 50% in 4 days. Intraperitoneal
bromodeoxyuridine (BrdU) incorporation and MIB-1 labeling decreased to 0%,
and the apoptosis was maximal at day 4. Androgen receptor expression and
prostate-specific antigen (PSA) serum levels decreased rapidly within 2
days. The number of NE cells increased 6-fold at day 4 and 30-fold at day
7. Five and ten percent of the CgA-positive cells were BrdU positive after
continuous BrdU labeling for 2 and 4 days, respectively. However, no MIB-1
expression was observed in CgA-positive cells. NE cells expressed the
regulated secretory pathway marker secretogranin III but were negative for
androgen receptor and Bcl-2. Bcl-2 expression did increase in the non-NE
tumor cells. In conclusion, androgen withdrawal leads to a rapid PC-295
tumor regression and a proliferation-independent induction of NE
differentiation. The strictly androgen-independent NE cells that were
still present after 21 days differentiated mainly from G0-phase-arrested
cells
Expression and prognostic value of Wilms' tumor 1 and early growth response 1 proteins in nephroblastoma
Wilms' tumor is one of the most common solid tumors of children. The
protein product of the tumor-suppressor gene, Wilms' tumor 1 (WT-1), binds
to the same DNA sequences as the protein product of the early growth
response 1 (EGR-1) gene. There is experimental evidence that EGR-1 is
involved in controlling cell growth. The expression of both genes in
Wilms' tumor was studied by others, mainly at the mRNA level. The present
study evaluates the prognostic value of WT-1 and EGR-1 in 61 Wilms' tumors
of chemotherapeutically treated patients at the protein level, using an
immunohistochemical approach. WT-1 was expressed in normal kidney tissues
and in the blastemal and epithelial component of Wilms' tumor, whereas
stromal tissue was negative. EGR-1 was expressed in normal kidney tissues
and in the three main cell types of Wilms' tumor. In 59 and 56% of Wilms'
tumor, the blastemal cells stained for WT-1 and EGR-1, respectively. The
blastemal expression of WT-1 and EGR-1 and the epithelial expression of
WT-1 were statistically significantly correlated with clinical stage. WT-1
immunoreactivity correlated with EGR-1 expression. Univariate analysis
showe
The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia A
Objectives:Ā Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities.Ā Methods:Ā All persons with hemophilia A (mild (FVIII > 5ā40 IU/dL)/moderate [FVIII 1ā5 IU/dL)/severe (FVIII < 1 IU/dL)] with an available plasma sample who participated in the sixth Hemophilia in the Netherlands study between 2018 and 2019 were included. The presence of anti-FVIII antibodies of the immunoglobulin A, M, and G isotypes and IgG subclasses, along with antibody titer levels, were assessed using direct-binding ELISAs. FVIII specificity was assessed using a competition-based ELISA approach. The inhibitor status was determined using the Nijmegen ultra-sensitive Bethesda assay (NusBA) and the Nijmegen Bethesda assay (NBA).Ā Results:Ā In total, 788 persons with hemophilia A (336 (42.6%) mild, 123 (15.6%) moderate, 329 (41.8%) severe hemophilia) were included. The median age was 45 years (IQR 24ā60), and the majority (50.9%) had over 150 exposure days to FVIII concentrates. Within our population, 144 (18.3%) individuals had non-neutralizing FVIII-specific antibodies, 10 (1.3%) had very low-titer inhibitors (NusBA positive; NBA negative), and 13 (1.6%) had inhibitors (both NusBA and NBA positive). IgG1 was the most abundant FVIII-specific antibody subclass, and the highest titer levels were found for IgG4. In individuals without a reported history of inhibitor development, no clear differences were observed in antibody patterns between those who were minimally or highly exposed to FVIII concentrates. IgG4 subclass antibodies were only observed in persons with a reported history of FVIII inhibitor or in those with a currently detected (very low-titer) inhibitor.Ā Conclusion:Ā In this cross-sectional study, we identified non-neutralizing antibodies in a relatively large proportion of persons with hemophilia A. In contrast, in our population, consisting of persons highly exposed to FVIII concentrates, (very low-titer) inhibitors were detected only in a small proportion of persons, reflecting a well-tolerized population. Hence, our findings suggest that only a small subpopulation of non-neutralizing FVIII-specific antibodies is associated with clinically relevant inhibitors.</p
The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia A
Objectives:Ā Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities.Ā Methods:Ā All persons with hemophilia A (mild (FVIII > 5ā40 IU/dL)/moderate [FVIII 1ā5 IU/dL)/severe (FVIII < 1 IU/dL)] with an available plasma sample who participated in the sixth Hemophilia in the Netherlands study between 2018 and 2019 were included. The presence of anti-FVIII antibodies of the immunoglobulin A, M, and G isotypes and IgG subclasses, along with antibody titer levels, were assessed using direct-binding ELISAs. FVIII specificity was assessed using a competition-based ELISA approach. The inhibitor status was determined using the Nijmegen ultra-sensitive Bethesda assay (NusBA) and the Nijmegen Bethesda assay (NBA).Ā Results:Ā In total, 788 persons with hemophilia A (336 (42.6%) mild, 123 (15.6%) moderate, 329 (41.8%) severe hemophilia) were included. The median age was 45 years (IQR 24ā60), and the majority (50.9%) had over 150 exposure days to FVIII concentrates. Within our population, 144 (18.3%) individuals had non-neutralizing FVIII-specific antibodies, 10 (1.3%) had very low-titer inhibitors (NusBA positive; NBA negative), and 13 (1.6%) had inhibitors (both NusBA and NBA positive). IgG1 was the most abundant FVIII-specific antibody subclass, and the highest titer levels were found for IgG4. In individuals without a reported history of inhibitor development, no clear differences were observed in antibody patterns between those who were minimally or highly exposed to FVIII concentrates. IgG4 subclass antibodies were only observed in persons with a reported history of FVIII inhibitor or in those with a currently detected (very low-titer) inhibitor.Ā Conclusion:Ā In this cross-sectional study, we identified non-neutralizing antibodies in a relatively large proportion of persons with hemophilia A. In contrast, in our population, consisting of persons highly exposed to FVIII concentrates, (very low-titer) inhibitors were detected only in a small proportion of persons, reflecting a well-tolerized population. Hence, our findings suggest that only a small subpopulation of non-neutralizing FVIII-specific antibodies is associated with clinically relevant inhibitors.</p
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