Perspective: Advancing the research agenda for improving understanding of cyanobacteria in a future of global change.

Harmful cyanobacterial blooms (=cyanoHABs) are an increasing feature of many waterbodies throughout the world. Many bloom-forming species produce toxins, making them of particular concern for drinking water supplies, recreation and fisheries in waterbodies along the freshwater to marine continuum. Global changes resulting from human impacts, such as climate change, over-enrichment and hydrological alterations of waterways, are major drivers of cyanoHAB proliferation and persistence. This review advocates that to better predict and manage cyanoHABs in a changing world, researchers need to leverage studies undertaken to date, but adopt a more complex and definitive suite of experiments, observations, and models which can effectively capture the temporal scales of processes driven by eutrophication and a changing climate. Better integration of laboratory culture and field experiments, as well as whole system and multiple-system studies are needed to improve confidence in models predicting impacts of climate change and anthropogenic over-enrichment and hydrological modifications. Recent studies examining adaptation of species and strains to long-term perturbations, e.g. temperature and carbon dioxide (CO2) levels, as well as incorporating multi-species and multi-stressor approaches emphasize the limitations of approaches focused on single stressors and individual species. There are also emerging species of concern, such as toxic benthic cyanobacteria, for which the effects of global change are less well understood, and require more detailed study. This review provides approaches and examples of studies tackling the challenging issue of understanding how global changes will affect cyanoHABs, and identifies critical information needs for effective prediction and management.

Early Detection of Infection Chains & Outbreaks: Use Case Infection Control.

Within the HiGHmed Project there are three medical use cases. The use cases include the scopes cardiology, oncology and infection. They serve to specify the requirements for the development and implementation of a local and federated platform, with the result that data from medical care and research should be retrievable, reusable and interchangeable. The Use Case Infection Control aims to establish an early detection of transmission events as well as clusters and outbreaks of various pathogens. Therefore the use case wants to establish the smart infection control system (SmICS).

Association of osteolytic lesions, bone mineral loss and trabecular sclerosis with prevalent vertebral fractures in patients with multiple myeloma.

PURPOSE: In patients with multiple myeloma (MM), computed tomography is widely used for staging and to detect fractures. Detecting patients at severe fracture risk is of utmost importance. However the criteria for impaired stability of vertebral bodies are not yet clearly defined. We investigated the performance of parameters that can be detected by the radiologist for discrimination of patients with and without fractures. METHODS AND MATERIALS: We analyzed 128 whole body low-dose CT of MM patients. In all scans a QCT calibration phantom was integrated into the positioning mat (Image Analysis Phantom(®)). A QCT-software (Structural Insight) performed the volumetric bone mineral density (vBMD) measurements. Description of fracture risk was provided from the clinical radiological report. Suspected progressive disease (PD) was reported by the referring clinicians. Two radiologists that were blinded to study outcome reported on the following parameters based on predefined criteria: reduced radiodensity in the massa lateralis of the os sacrum (RDS), trabecular thickening and sclerosis of three or more vertebrae (TTS), extraosseous MM manifestations (EOM), visible small osteolytic lesions up to a length of 8mm (SO) and osteolytic lesions larger than 8mm (LO). Prevalent vertebral fractures (PVF) were defined by Genant criteria. Age-adjusted standardized odds ratios (sOR) per standard deviation change were derived from logistic regression analysis and area under the curve (AUC) from receiver operating characteristics (ROC) analyses were calculated. ROC curves were compared using the DeLong method. RESULTS: 45% of the 128 patients showed PVF (29 of 75 men, 24 of 53 women). Patients with PVF were not significantly older than patients without fractures (64.6 ± 9.2 vs. 63.3 ± 12.3 years: mean ± SD, p=0.5). The prevalence of each parameter did not differ significantly by sex. Significant fracture discrimination for age adjusted single models was provided by the parameters vBMD (OR 3.5 [1.4-8.8], AUC=0.64 ± 0.14), SO (sOR 1.6[1.1-2.2], AUC=0.63 ± 0.05), LO (sOR 2.1[1.1-4.2] AUC=0.69 ± 0.05) and RDS (sOR 2.6[1.6-4.7], AUC=0.69 ± 0.05). Multivariate models of these four parameters showed a significantly stronger association with the development of PVF (AUC=0.80 ± 0.04) than single variables. TTS showed a significant association with PVF in men(sOR 1.5 [0.8-3.0], AUC=0.63 ± 0.08), but not in women (sOR 2.3[1.4-3.7], AUC=0.70 ± 0.07). PD was significantly associated with PVF in women (sOR 1.9[1.1-3.6], AUC=0.67 ± 0.08) but not in men (sOR 1.4[0.9-2.3], AUC=0.57 ± .07). EOM were not associated with PVF (sOR 1.0[0.4-2.6], AUC=0.51 ± .05). CONCLUSION: In multiple myeloma, focal skeletal changes in low dose CT scans show a significant association with prevalent vertebral fractures. The combination of large osteolytic lesions and loss in radiodensity as can be detected with simple CT Hounsfield measurements of the os sacrum or BMD measurements showed the strongest association to fractures and may be of value for prospective studies.

Comparison of manual and semi-automatic measuring techniques in MSCT scans of patients with lymphoma: a multicentre study.

OBJECTIVES: Multicentre evaluation of the precision of semi-automatic 2D/3D measurements in comparison to manual, linear measurements of lymph nodes regarding their inter-observer variability in multi-slice CT (MSCT) of patients with lymphoma. METHODS: MSCT data of 63 patients were interpreted before and after chemotherapy by one/two radiologists in five university hospitals. In 307 lymph nodes, short (SAD)/long (LAD) axis diameter and WHO area were determined manually and semi-automatically. Volume was solely calculated semi-automatically. To determine the precision of the individual parameters, a mean was calculated for every lymph node/parameter. Deviation of the measured parameters from this mean was evaluated separately. Statistical analysis entailed intraclass correlation coefficients (ICC) and Kruskal-Wallis tests. RESULTS: Median relative deviations of semi-automatic parameters were smaller than deviations of manually assessed parameters, e.g. semi-automatic SAD 5.3 vs. manual 6.5 %. Median variations among different study sites were smaller if the measurement was conducted semi-automatically, e. g. manual LAD 5.7/4.2 % vs. semi-automatic 3.4/3.4 %. Semi-automatic volumetry was superior to the other parameters (2.8 %). CONCLUSIONS: Semi-automatic determination of different lymph node parameters is (compared to manually assessed parameters) associated with a slightly greater precision and a marginally lower inter-observer variability. These results are with regard to the increasing mobility of patients among different medical centres and in relation to the quality management of multicentre trials of importance. KEY POINTS: • In a multicentre setting, semi-automatic measurements are more accurate than manual assessments. • Lymph node volumetry outperforms all other semi-automatically and manually performed measurements. • Use of semi-automatic lymph node analyses can reduce the inter-observer variability.

Therapy response evaluation of malignant lymphoma in a multicenter study: comparison of manual and semiautomatic measurements in CT.

PURPOSE: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. MATERIALS AND METHODS: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. RESULTS: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. CONCLUSION: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. KEY POINTS: ► Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients ► Manual lymph node evaluation with uni-dimensional parameters is inferior to semi-automatic analysis in a multicenter setting ► Semi-automatic quantitative software tools should be introduced in clinical study evaluation.

Volumetric response classification in metastatic solid tumors on MSCT: initial results in a whole-body setting.

PURPOSE: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. MATERIALS AND METHODS: 56 consecutive patients (32 female) aged 41-82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. RESULTS: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p<0.05, corrected). 4-8 patients' response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. CONCLUSION: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

Comparison of noninvasive imaging modalities for stenosis grading in mesenteric arteries.

OBJECTIVE: To prospectively analyze duplex sonography, CTA, and MRA with respect to stenosis grading of the celiac trunk (TC) and the superior mesenteric artery (SMA), with DSA as the reference. MATERIALS AND METHODS: 52 subjects were enrolled (mean age: 71). The image quality was graded: 1-insufficient, 2-bad, 3-moderate, 4-good or 5-excellent. Stenosis was graded: 1 (< 25 %), 2 (25 - < 50 %), 3 (50 - 75 %) or 4 (75 %). Two-sided chi-square tests were used to check for correlation of stenosis grading between modalities. The weighted Cohen's kappa was calculated to assess the strength of correlation. With a threshold of 50 % for non-relevant stenosis vs. relevant stenosis, the sensitivity, specificity, PPV, NPV, and accuracy were calculated. RESULTS: The mean image quality was 3.8 ± 0.7, 3.1 ± 1.0, 4.4 ± 0.7, and 3.8 ± 0.9 for DSA, duplex sonography, CTA, and MRA, respectively. For both TC and SMA, stenosis grading reached a significant level of correlation between each noninvasive modality with DSA (p < 0.001, each). The weighted Cohen's kappa for duplex sonography/CTA/MRA was 0.94/0.93/0.74, respectively, for the TC and 0.64/0.91/0.56, respectively, for the SMA. Highest sensitivity/specificity/NPV/PPV/accuracy were found for CTA with 100 %/95 %/85 %/100 %/96 % for the TC and with na/98 %/na/100 %/98 %, respectively, for the SMA. CONCLUSION: CTA provided the best image quality, reached the highest level of agreement and significance in correlation in stenosis grading, and offered the best diagnostic accuracy.

Outcome of immediate interventions in acute dysfunctional hemodialysis fistulas.

PURPOSE: To analyze the efficacy of interventions in acute dysfunctional hemodialysis fistulas, if intervention is performed immediately as recommended by European Best Practice Guidelines for Hemodialysis. MATERIALS AND METHODS: Over 3 years, all (n = 280) patients with an acute dysfunctional hemodialysis fistula were immediately referred to angiography, irrespective of the time of day. Angiography and, if possible, interventional revision (n = 241) were performed. Three groups of interest were established: interventionalist's experience (high/low), time of day (routine hours: 7 am-4 pm/emergency hours: 4 pm-7 am), lesion type (stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+thrombotic occlusion). For statistical analysis corresponding success rates, chi-square tests (p < 0.025) and logistic regression analysis (p < 0.05) were calculated. RESULTS: The total success rate was 62 % (149/241). The success rates were: interventionalist experience high/low 71 % (79/111)/54 % (70/130), p = 0.022; time of day routine/emergency hours 68 % (93/136)/53 % (56/105), p = 0.017; lesion type stenosis/fibrosclerotic occlusion/thrombotic occlusion/combined stenosis+occlusion 82 % (94/104)/39 % (13/33)/18 % (6/33)/59 % (36/61), p < 0.001. Relevant variables due to logistic regression analysis were high experience and the lesion types stenosis and combined stenosis+occlusion with odds ratios 2.300 (p = 0.012), 12.053 (p < 0.001), 3.189 (p = 0.003). CONCLUSION: Unrestricted implementation of immediate interventions in acute dysfunctional hemodialysis fistulas requires permanent availability of experienced interventionalists. The lesion types fibrosclerotic occlusion and thrombotic occlusion offer poor success rates for interventional revision.

Lung, liver and lymph node metastases in follow-up MSCT: comprehensive volumetric assessment of lesion size changes.

PURPOSE: To investigate measurement accuracy in terms of precision and inter-rater variability in the simultaneous volumetric assessment of lung, liver and lymph node metastasis size change over time in comparison to RECIST 1.1. MATERIALS AND METHODS: Three independent readers evaluated multislice CT data from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually (RECIST 1.1) and by volumetry with semi-automated software. The quality of segmentation and need for manual adjustments were recorded. Volumes were converted to effective diameters to allow comparison to RECIST. For statistical assessment of precision and interobserver agreement, the Wilcoxon-signed rank test and Bland-Altman plots were utilized. RESULTS: The quality of segmentation after manual correction was acceptable to excellent in 95 % of lesions and manual corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective) relative measurement deviation (p <.001). Inter-reader median variation coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for different lesion types (p < .001). The limits of agreement were ± 9.8 to ± 11.2 % for volumetric assessment. CONCLUSION: Superior precision and inter-rater variability of volumetric over manual measurement of lesion change over time was demonstrated in a whole body setting.

Clinical lymph node staging--influence of slice thickness and reconstruction kernel on volumetry and RECIST measurements.

PURPOSE: Therapy response evaluation in oncological patient care requires reproducible and accurate image evaluation. Today, common standard in measurement of tumour growth or shrinkage is one-dimensional RECIST 1.1. A proposed alternative method for therapy monitoring is computer aided volumetric analysis. In lung metastases volumetry proved high reliability and accuracy in experimental studies. High reliability and accuracy of volumetry in lung metastases has been proven. However, other metastatic lesions such as enlarged lymph nodes are far more challenging. The aim of this study was to investigate the reproducibility of semi-automated volumetric analysis of lymph node metastases as a function of both slice thickness and reconstruction kernel. In addition, manual long axis diameters (LAD) as well as short axis diameters (SAD) were compared to automated RECIST measurements. MATERIALS AND METHODS: Multislice-CT of the chest, abdomen and pelvis of 15 patients with lymph node metastases of malignant melanoma were included. Raw data were reconstructed using different slice thicknesses (1-5 mm) and varying reconstruction kernels (B20f, B40f, B60f). Volume and RECIST measurements were performed for 85 lymph nodes between 10 and 60 mm using Oncology Prototype Software (Fraunhofer MEVIS, Siemens, Germany) and were compared to a defined reference volume and diameter by calculating absolute percentage errors (APE). Variability of the lymph node sizes was computed as relative measurement differences, precision of measurements was computed as relative measurement deviation. RESULTS: Mean absolute percentage error (APE) for volumetric analysis varied between 3.95% and 13.8% and increased significantly with slice thickness. Differences between reconstruction kernels were not significant, however, a trend towards middle soft tissue kernel could be observed.. Between automated and manual short axis diameter (SAD, RECIST 1.1) and long axis diameter (LAD, RECIST 1.0) no significant differences were found. The most unsatisfactory segmentation results occurred in higher slice thickness (3 and 5 mm) and sharp tissue kernel. CONCLUSION: Volumetric analysis of lymph nodes works satisfying in a clinical setting. Thin slice reconstructions (≤3 mm) and a middle soft tissue reconstruction kernel are recommended. LAD and SAD did not show significant differences regarding APE. Automated RECIST measurement showed lower APE than manual measurement in trend.

Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats.

BACKGROUND AND PURPOSE: Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes. EXPERIMENTAL APPROACH: Male ZDF rats were treated with oral sCT (0.5, 1.0 or 2 mg·kg(-1) ) or oral vehicle twice daily from age 8 to 18 weeks. Zucker lean rats served as control group. Fasting and non-fasted blood glucose, glycosylated haemoglobin (HbA1c) and levels of pancreas and incretin hormones were determined. Oral glucose tolerance test and i.p. glucose tolerance test were compared, and beta-cell area and function were evaluated. KEY RESULTS: Oral sCT treatment dose-dependently attenuated fasting and non-fasted hyperglycaemia during the intervention period. At the end of the study period, oral sCT treatment by dose decreased diabetic hyperglycaemia by ∼9 mM and reduced HbA1c levels by 1.7%. Furthermore, a pronounced reduction in glucose excursions was dose-dependently observed for oral sCT treatment during oral glucose tolerance test. In addition, oral sCT treatment sustained hyperinsulinaemia and attenuated hyperglucagonaemia and hypersecretion of total glucagon-like peptide-1 predominantly in the basal state. Lastly, oral sCT treatment dose-dependently improved pancreatic beta-cell function and beta-cell area at study end. CONCLUSIONS AND IMPLICATIONS: Oral sCT attenuated diabetic hyperglycaemia in male ZDF rats by improving postprandial glycaemic control, exerting an insulinotropic and glucagonostatic action in the basal state and by preserving pancreatic beta-cell function and beta-cell area.

Severe developmental bone phenotype in ClC-7 deficient mice.

Bone development is dependent on the functionality of three essential cell types: chondrocytes, osteoclasts and osteoblasts. If any of these cell types is dysfunctional, a developmental bone phenotype can result. The bone disease osteopetrosis is caused by osteoclast dysfunction or impaired osteoclastogenesis, leading to increased bone mass. In ClC-7 deficient mice, which display severe osteopetrosis, the osteoclast malfunction is due to abrogated acidification of the resorption lacuna. This study sought to investigate the consequences of osteoclast malfunction on bone development, bone structure and bone modeling/remodeling in ClC-7 deficient mice. Bones from wildtype, heterozygous and ClC-7 deficient mice were examined by bone histomorphometry and immunohistochemistry. ClC-7 deficient mice were found to have a severe developmental bone phenotype, characterized by dramatically increased bone mass, a high content of cartilage remnants, impaired longitudinal and radial growth, as well as lack of compact cortical bone development. Indices of bone formation were reduced in ClC-7 deficient mice; however, calcein labeling indicated that mineralization occurred on most trabecular bone surfaces. Osteoid deposition had great regional variance, but an osteopetrorickets phenotype, as observed in oc/oc mice, was not apparent in the ClC-7 deficient mice. A striking finding was the presence of very large abnormal osteoclasts, which filled the bone marrow space within the ClC-7 deficient bones. The development of these giant osteoclasts could be due to altered cell fate of the ClC-7 deficient osteoclasts, caused by increased cellular fusion and/or prolonged osteoclast survival. In summary, malfunctional ClC-7 deficient osteoclasts led to a severe developmental bone phenotype including abnormally large and non-functional osteoclasts. Bone formation paremeters were reduced; however, bone formation and mineralization were found to be heterogenous and continuing.

Advances in osteoclast biology resulting from the study of osteopetrotic mutations.

Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast phenotypes, we discuss how osteopetrosis models have clarified the function of the coupling of bone formation to bone resorption, and the pivotal role of the osteoclast and their function in this phenomenon. We highlight the distinct possibility that osteoclast activities can be divided into two separate avenues: bone resorption and control of bone formation.

The tufB-secE-nusG-rplKAJL-rpoB gene cluster of the liberibacters: sequence comparisons, phylogeny and speciation.

The rplKAJL-rpoBC operon or beta operon is a classic bacterial gene cluster, which codes for proteins K, A, J and L of the large ribosomal subunit, as well as proteins B (beta subunit) and C (beta' subunit) of RNA polymerase. In the early 1990s, the operon was obtained as a 2.6 kbp DNA fragment (In-2.6) by random cloning of DNA from periwinkle plants infected with the Poona (India) strain of the huanglongbing agent, later named 'Candidatus (Ca.) Liberibacter asiaticus'. DNA from periwinkle plants infected with the Nelspruit strain (South Africa) of 'Ca. L. africanus' was amplified with a primer pair designed from In-2.6 and yielded, after cloning and sequencing, a 1.7 kbp DNA fragment (AS-1.7) of the beta operon of 'Ca. L. africanus'. The beta operon of the American liberibacter, as well as the three upstream genes (tufB, secE, nusG), have now also been obtained by the technique of chromosome walking and extend over 4673 bp, comprising the following genes: tufB, secE, nusG, rplK, rplA, rplJ, rplL and rpoB. The sequence of the beta operon was also determined for a Brazilian strain of 'Ca. L. asiaticus', from nusG to rpoB (3025 bp), and was found to share 99 % identity with the corresponding beta operon sequences of an Indian and a Japanese strain. Finally, the beta operon sequence of 'Ca. L. africanus' was extended from 1673 bp (rplA to rpoB) to 3013 bp (nusG to rpoB), making it possible to compare the beta operon sequences of the African, Asian and American liberibacters over a length of approximately 3000 bp, from nusG to rpoB. While 'Ca. L. africanus' and 'Ca. L. asiaticus' shared 81.2 % sequence identity, the percentage for 'Ca. L. americanus' and 'Ca. L. africanus' was only 72.2 %, and identity for 'Ca. L. americanus' and 'Ca. L. asiaticus' was only 71.4 %. The approximately 3000 bp nusG-rpoB sequence was also used to construct a phylogenetic tree, and this tree was found to be identical to the known 16S rRNA gene sequence-based tree. These results confirm earlier findings that 'Ca. L. americanus' is a distinct liberibacter, more distantly related to 'Ca. L. africanus' and 'Ca. L. asiaticus' than 'Ca. L. africanus' is to 'Ca. L. asiaticus'. The dates of speciation have also been estimated.

Pathogenicity of axenic Steinernema feltiae, Xenorhabdus bovienii, and the bacto-helminthic complex to larvae of Tipula oleracea (Diptera) and Galleria mellonella (Lepidoptera).

The pathogenicity of the nematode-bacterium complex Steinernema feltiae-Xenorhabdus bovienii to larvae of Tipula oleracea and Galleria mellonella was investigated by injection of dauer juvenile nematodes carrying their bacterial symbiont cells (monoxenic nematodes). Axenic nematodes (free of bacteria) and the symbiotic bacteria themselves were tested. The LC50 of X. bovienii in T. oleracea was 15,700 colony forming units (CFU)/larva compared to < or = 8 CFU in G. mellonella. Xenorhabdus bovienii is apparently removed from the tipulids hemolymph, possibly by cellular defense mechanisms. Axenic nematodes were less pathogenic than monoxenic nematodes for both insects. The difference was less pronounced in G. mellonella larvae: one axenic nematode was sufficient to kill 80% in 1 day. The remaining insects found dead after 50 days were developmentally arrested. In T. oleracea 20 axenic nematodes caused 39% whereas 20 monoxenic dauer juveniles caused 90% mortality within 8 days. The data indicate that the virulence of the S. feltiae/X. bovienii complex is greater than the additive effect of the nematodes and their bacteria, further evidence for the synergistic activity of the symbiotic bacto-helminthic complex during pathogenesis.

The effect of the interval between dose applications on the observed specific-locus mutation rate in the mouse following fractionated treatments of spermatogonia with ethylnitrosourea.

Our earlier analyses have suggested an apparent threshold dose-response for ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102 x C3H)F1 mice were exposed to 4 x 10, 2 x 40. 4 x 20 or 4 x 40 mg ethylnitrosourea per kg body weight with 24 h between applications; 4 x 40 mg ethylnitrosourea per kg body weight with 72 h between dose applications; and 2 x 40, 4 x 20 and 4 x 40 mg ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.

Psychosocial characteristics of asthma.

The objective of this study was to compare psychosocial characteristics of children with asthma and children with bronchial hyperreactivity with those of normal children. A population-based study of 2634 children (mean age, 10 years) was carried out. Pulmonary function tests of children were performed in children before and after cold air hyperventilation challenge to determine bronchial hyperreactivity. Parental assessment of children's behavior was evaluated with 15 questions about school/learning habits, level of activity, communication/affection, and sleeping patterns. A factor analysis was performed and the factor loading adjusted for confounders compared in the different groups. Asthmatic children sleep less well than normal and hyperreactive children (p < 0.001). Unexpectedly, however, all other single items did not differ significantly. As a result of the factorial analysis we obtained two factors. On the first factor, measuring school behavior and learning, there was a small difference between asthmatic and normal children, which could not be found on the second factor indicating activity and communication. We conclude that psychosocial differences of asthmatic children are less remarkable than expected. As a result of the examination of the hyperreactive children it is likely that asthmatic children are influenced more by secondary psychosocial factors than by any primary effect of asthmatic disease.

Serial potentiometric and conductometric detection in fast non-suppressed ion chromatography applied to the analysis of filter collected airborne particulates.

Non-suppressed ion chromatography (NSIC) has been optimized to permit the determination of chloride, nitrate and sulfate in the low mg/l concentration range within 3 min. Using conductometric detection the extraneous (positive) injection peak was found to adversely affect the early eluting chloride signal when samples with high amounts of total cations are analyzed. The serial arrangement of a downstream potentiometric detector with a chloride ion selective electrode, which does not respond to other alterations of the composition of the eluent than the change in chloride concentrations, is shown to be suitable for interference-free, sensitive and reliable chloride evaluation. Application of the proposed system to the determination of chloride in extracts of filter collected airborne particulates revealed (for those samples that could be evaluated by both detection methods) high precision and no systematic deviations between conductometric and potentiometric detection.

Photodynamic action of ultraviolet A: induction of cellular hydroperoxides.

Long-wavelength ultraviolet radiation (UVA) can cause cancer. A carcinogenic mechanism involved may be the induction of harmful reactive oxygen species resulting from photodynamic effects. UVA is generally assumed to induce photodynamic effects, but evidence from experiments with viable biological materials has been indirect until present. Here we measured the induction of (lipid) hydroperoxides as direct indicators of photodynamic reactions. Cultured human fibroblasts were irradiated with 10J UVA/cm2. The induced hydroperoxides were measured by an enzymatic method using glutathione peroxidase and glutathione reductase (GR). Additionally, reduced glutathione (GSH) was determined as parameter for the constitutive antioxidant defense. UVA was found to increase lipid hydroperoxides in fibroblasts by 116% (p < 0.001), when compared to nonirradiated controls. Conversely GSH was decreased in the irradiated cells by 51% (p < 0.001). Because of the induced hydroperoxides, it is concluded that the UVA effects were mediated by a photodynamic mechanism. The photodynamic mechanism resulted in the formation of reactive oxygen species and the consumption of constitutive antioxidants. This suggests a role for antioxidants during the photodynamic mechanism. Photodynamic mechanisms may play a crucial role in carcinogenic events, especially after UVA.