Determinants of hepato- and spleno-megaly in Hunan, China: cross-sectional survey data from areas endemic for schistosomiasis

In order to understand the determinants of schistosome-related hepato- and spleno-megaly better, 14 002 subjects aged 3-60 years (59% male; mean age =32 years) were randomly selected from 43 villages, all in Hunan province, China, where schistosomiasis caused by Schistosoma japonicum is endemic. The abdomen of each subject was examined along the mid-sternal (MSL) and mid-clavicular lines, for evidence of current hepato- and/or spleno-megaly, and a questionnaire was used to collect information on the medical history of each individual. Current infections with S. japonicum were detected by stool examination. Almost all (99.8%) of the subjects were ethnically Han by descent and most (77%) were engaged in farming. Although schistosomiasis appeared common (42% of the subjects claiming to have had the disease), only 45% of the subjects said they had received anti-schistosomiasis drugs. Overall, 1982 (14%) of the subjects had S. japonicum infections (as revealed by miracidium-hatching tests and/or Katon Katz smears) when examined and 22% had palpable hepatomegaly (i.e. enlargement of at least 3 cm along the MSL), although only 2.5% had any form of detectable splenomegaly (i.e. a Hackett's grade of at least 1). Multiple logistic regression revealed that male subjects, fishermen, farmers, subjects aged greater than or equal to 25 years, subjects with a history of schistosomiasis, and subjects who had had bloody stools in the previous 2 weeks were all at relatively high risk of hepato- and/or spleno-megaly. In areas moderately endemic for Schistosoma japonicum, occupational exposure and disease history appear to be good predictors of current disease status among older residents. These results reconfirm those reported earlier in the same region.

A sociolinguistic approach to applied epistemology: Examining technocratic values in global 'knowledge' policy

This special issue presents an excellent opportunity to study applied epistemology in public policy. This is an important task because the arena of public policy is the social domain in which macro conditions for ‘knowledge work’ and ‘knowledge industries’ are defined and created. We argue that knowledge-related public policy has become overly concerned with creating the politico-economic parameters for the commodification of knowledge. Our policy scope is broader than that of Fuller (1988), who emphasizes the need for a social epistemology of science policy. We extend our focus to a range of policy documents that include communications, science, education and innovation policy (collectively called knowledge-related public policy in acknowledgement of the fact that there is no defined policy silo called ‘knowledge policy’), all of which are central to policy concerned with the ‘knowledge economy’ (Rooney and Mandeville, 1998). However, what we will show here is that, as Fuller (1995) argues, ‘knowledge societies’ are not industrial societies permeated by knowledge, but that knowledge societies are permeated by industrial values. Our analysis is informed by an autopoietic perspective. Methodologically, we approach it from a sociolinguistic position that acknowledges the centrality of language to human societies (Graham, 2000). Here, what we call ‘knowledge’ is posited as a social and cognitive relationship between persons operating on and within multiple social and non-social (or, crudely, ‘physical’) environments. Moreover, knowing, we argue, is a sociolinguistically constituted process. Further, we emphasize that the evaluative dimension of language is most salient for analysing contemporary policy discourses about the commercialization of epistemology (Graham, in press). Finally, we provide a discourse analysis of a sample of exemplary texts drawn from a 1.3 million-word corpus of knowledge-related public policy documents that we compiled from local, state, national and supranational legislatures throughout the industrialized world. Our analysis exemplifies a propensity in policy for resorting to technocratic, instrumentalist and anti-intellectual views of knowledge in policy. We argue that what underpins these patterns is a commodity-based conceptualization of knowledge, which is underpinned by an axiology of narrowly economic imperatives at odds with the very nature of knowledge. The commodity view of knowledge, therefore, is flawed in its ignorance of the social systemic properties of ��knowing’.

Estimation of body water compartments in cirrhosis by multiple-frequency bioelectrical-impedance analysis

Estimation of total body water by measuring bioelectrical impedance at a fixed frequency of 50 kHz is useful in assessing body composition in healthy populations. However, in cirrhosis, the distribution of total body water between the extracellular and intracellular compartments is of greater clinical importance. We report an evaluation of a new multiple-frequency bioelectrical-impedance analysis technique (MFBIA) that may quantify the distribution of total body water in cirrhosis. In 21 cirrhotic patients and 21 healthy control subjects, impedance to the Row of current was measured at frequencies ranging from 4 to 1012 kHz. These measurements were used to estimate body water compartments and then compared with total body water and extracellular water determined by isotope methodology. In cirrhotic patients, extracellular water and total body water (as determined by isotope methods) were well predicted by MFBIA (r = 0.73 and 0.89, respectively).;However, the 95% confidence intervals of the limits of agreement between MFBIA and the isotope methods were +/- 14% and +/-9% for cirrhotics (extracellular water and total body water, respectively) and +/-9% and +/-9% for cirrhotics without ascites. The 95% confidence intervals estimated from the control group were +/-10% and +/-5% for extracellular water and total body water, respectively. Thus, despite strong correlations between MFBIA and isotope measurements, the relatively large limits of agreement with accepted techniques suggest that the MFBIA technique requires further refinement before it can be routinely used to determine the nutritional assessment of individual cirrhotic patients. Nutrition 2001,17.31-34. (C)Elsevier Science Inc. 2001.

A molecular comparison of T lymphocyte populations infiltrating the liver and circulating in the blood of patients with chronic hepatitis B: Evidence for antigen-driven selection of a public complementarity-determining region 3 (CDR3) motif

Despite a large number of T cells infiltrating the liver of patients with chronic hepatitis B, little is known about their complexity or specificity. To characterize the composition of these T cells involved with the pathogenesis of chronic hepatitis B (CHB), we have studied the clonality of V beta T cell receptor (TCR)-bearing populations in liver tissue by size spectratyping the complementarity-determining region (CDR3) lengths of TCR transcripts. We have also compared the CDR3 profiles of the lymphocytes infiltrating the liver with those circulating in the blood to see whether identical clonotypes may be detected that would indicate a virus-induced expansion in both compartments. Our studies show that in most of the patients examined, the T cell composition of liver infiltrating lymphocytes is highly restricted, with evidence of clonotypic expansions in 4 to 9 TCR V beta subfamilies. In contrast, the blood compartment contains an average of 1 to 3 expansions. This pattern is seen irrespective of the patient's viral load or degree of liver pathology. Although the TCR repertoire profiles between the 2 compartments are generally distinct, there is evidence of some T cell subsets being equally distributed between the blood and the liver. Finally, we provide evidence for a putative public binding motif within the CDR3 region with the sequence G-X-S, which may be involved with hepatitis B virus recognition.

Suppression of keratinocyte growth and differentiation by transforming growth factor beta 1 involves multiple signaling pathways

Transforming growth factor beta1 treatment of keratinocytes results in a suppression of differentiation, an induction of extracellular matrix production, and a suppression of growth. In this study we utilized markers specific for each of these functions to explore the signaling pathways involved in mediating these transforming-growth-factor-beta1-induced activities. In the first instance, we found that the induction of extracellular matrix production (characterized by 3TP-Lux reporter activity) was induced in both keratinocytes and a keratinocyte-derived carcinoma cell line, SCC25, in a dose-dependent manner. Furthermore, transforming growth factor beta1 also suppressed the differentiation-specific marker gene, transglutaminase type 1, in both keratinocytes and SCC25 cells. In contrast, transforming growth factor beta1 inhibited proliferation of keratinocytes but did not cause growth inhibition in the SCC25 cells. Transforming-growth-factor-beta1-induced growth inhibition of keratinocytes was characterized by decreases in DNA synthesis, accumulation of hypophosphorylated Rb, and the inhibition of the E2F:Rb-responsive promoter, cdc2, and an induction of the p21 promoter. When the negative regulator of transforming growth factor beta1 signaling, SMAD7, was overexpressed in keratinocytes it could prevent transforming-growth-factor-beta1-induced activation of the 3TP-Lux and the p21 promoter. SMAD7 could also prevent the suppression of the transglutaminase type 1 by transforming growth factor beta1 but it could not inhibit the repression of the cdc2 promoter. These data indicate that the induction of 3TP-Lux and p21 and the suppression of transglutaminase type 1 are mediated by a different proximate signaling pathway to that regulating the suppression of the cdc2 gene. Combined, these data indicate that the regulation of transforming growth factor beta1 actions are complex and involve multiple signaling pathways.

Early diagnosis of lymphedema using multiple frequency bioimpedance

Multiple frequency bioelectrical impedance analysis (MFBIA) has previously been shown to provide accurate relative measures of lymphedema in the upper limb of patients (1). This paper reports the results of a three year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in patients following treatment for breast cancer. Bioelectrical impedance measurements and circumferential measurements of each upper limb were recorded in healthy control subjects (n=60) to determine the normal range of the ratio (dominant/non-dominant) of extracellular and total limb volumes respectively. Patients undergoing surgery for the treatment of breast cancer were recruited as the study group; MFBIA and circumferential measurements were recorded pre-surgery, one month post-surgery and then at two month intervals for 24 months. One hundred and two patients were recruited into the study. Twenty patients developed lymphedema in the 24 months follow up period of this study. In each of these 20 cases MFBIA predicted the onset of the condition up to 10 months before the condition could be clinically diagnosed. Estimates of the sensitivity and specificity were both approximately 100%. At the time of detection by MFBIA, only one of the patients returned a positive test result from the total limb volumes determined from the circumferential measures. These results confirmed the suitability of the MFBIA technique as a reliable diagnostic procedure for the early detection of lymphedema.

Stem cells in the aetiopathogenesis and therapy of rheumatic disease

Animal models of autoimmune disease and case reports of patients with these diseases who have been involved in bone marrow transplants have provided important data implicating the haemopoietic stem cell in rheumatic disease pathogenesis. Animal and human examples exist for both cure and transfer of rheumatoid arthritis, systemic lupus erythematosus (SLE) and other organ-specific diseases using allogeneic haemopoietic stem cell transplantation. This would suggest that the stem cell in these diseases is abnormal and could be cured by replacement of a normal stem cell although more in vitro data are required in this area. Given the morbidity and increased mortality in some patients with severe autoimmune diseases and the increasing safety of autologous haemopoietic stem cell transplantation (HSCT), pilot studies have been conducted using HSCT in rheumatic diseases. It is still unclear whether an autologous graft will cure these diseases but significant remissions have been obtained which have provided important data for the design of randomized trials of HSCT versus more conventional therapy. Several trials are now open to accrual under the auspices of the European Bone Marrow Transplant Group/European League Against Rheumatism (EBMT/EULAR) registry. Future clinical and laboratory research will need to document the abnormalities of the stem cell of a rheumatic patient because new therapies based on gene therapy or stem cell differentiation could be apllied to these diseases. With increasing safety of allogeneic HSCT it is not unreasonable to predict cure of some rheumatic diseases in the near future.

Multiple bifurcations in atom optics

We report the observation of multiple bifurcations in a nonlinear Hamiltionian system: laser-cooled atoms in a standing wave with single-frequency intensity modulation. We provide clear evidence of the occurrence of bifurcations by analyzing the atomic momentum distributions.

Pectenotoxins - an issue for public health - A review of their comparative toxicology and metabolism

Pectenotoxins (PTXs) are a group of toxins associated with diarrhetic shellfish poisoning (DSP) and isolated from DSP toxin-producing dinoflagellate algae. Consumption of shellfish contaminated with PTXs has been associated with incidences of severe diarrhetic illness resulting in hospitalisation. Concern has been raised for public health following the discovery that these toxins are not only hepatotoxic and can cause diarrhetic effects in mammals, but that they are potently cytotoxic to human cancer cell lines and have been found to be tumour promoters in animals. With advances in knowledge and technology, more PTXs are being identified, but little is known of their toxicology and the potential impact these toxins may have on public health in the long term. Without such information, adequate health-risk assessments for the consumption of shellfish contaminated with PTXs cannot be performed. This review gives a brief introduction to diarrhetic shellfish toxins, details the known toxicology and metabolism of PTXs in animals, and discusses known incidences of PTX poisoning in humans. (C) 2001 Elsevier Science Ltd. All rights reserved.

Fluorescence spectrum of a two-level atom driven by a multiple modulated field

We investigate the fluorescence spectrum of a two-level atom driven by a multiple amplitude-modulated field. The driving held is modeled as a polychromatic field composed of a strong central (resonant) component and a large number of symmetrically detuned sideband fields displaced from the central component by integer multiples of a constant detuning. Spectra obtained here differ qualitatively from those observed for a single pair of modulating fields [B. Blind, P.R. Fontana, and P. Thomann, J. Phys. B 13, 2717 (1980)]. In the case of a small number of the modulating fields, a multipeaked spectrum is obtained with the spectral features located at fixed frequencies that are independent of the number of modulating fields and their Rabi frequencies. As the number of the modulating fields increases, the spectrum ultimately evolves to the well-known Mellow triplet with the sidebands shifted from the central component by an effective Rabi frequency whose magnitude depends on the initial relative phases of the components of the driving held. For equal relative phases, the effective Rabi frequency of the driving field can be reduced to zero resulting in the disappearance of fluorescence spectrum, i.e., the atom can stop interacting with the field. When the central component and the modulating fields are 180 degrees out of phase, the spectrum retains its triplet structure with the sidebands located at frequencies equal to the sum of the Rabi frequencies of the component of the driving field. Moreover, we shaw that the frequency of spontaneous emission can be controlled and switched from one frequency to another when the Rabi frequency or initial phase of the modulating fields are varied.