Monitoring and risk assessment of hazardous chemicals in toy-slime and putty in the Netherlands.

In 2019, the Dutch Food and Consumer Product Safety Authority performed a market surveillance for toy-slime (23 samples) and putty (16 samples). For 35% of the toy-slimes and 13% of the putties, the migration of boron exceeded the European legal limit of 300 and 1200 mg/kg respectively. In 36% of the toy samples, methylisothiazolinone (MI) and chloromethylisothiazolinone (CMI) were detected in levels up to 25 and 38 mg/kg, respectively, much higher than the European legal limit for aqueous toys intended for children younger than three. 59% of the toys contained other preservatives such as 2-phenoxyethanol, p-hydroxybenzoic acid and parabens. In 2 toy-slimes and 2 putties N-nitrosodiethanolamine (NDELA) was found in amounts up to 2.3 mg/kg. A risk assessment was performed for boron and NDELA. The estimated exposure to boron did not exceed the health based guidance value. The estimated exposure to NDELA from 2 toy-slimes may pose a health risk. For 2 putties the estimated exposure to NDELA was somewhat lower, but health risks could not be excluded. The presence of isothiazolinones may lead to skin sensitisation. It is recommended to extend the legal limit for NDELA, MI and CMI in finger-paint and labelling requirements to other aqueous toys.

Predicting pregnancy status from mid-infrared spectroscopy in dairy cow milk using deep learning.

Accurately identifying pregnancy status is imperative for a profitable dairy enterprise. Mid-infrared (MIR) spectroscopy is routinely used to determine fat and protein concentrations in milk samples. Mid-infrared spectra have successfully been used to predict other economically important traits, including fatty acid content, mineral content, body energy status, lactoferrin, feed intake, and methane emissions. Machine learning has been used in a variety of fields to find patterns in vast quantities of data. This study aims to use deep learning, a sub-branch of machine learning, to establish pregnancy status from routinely collected milk MIR spectral data. Milk spectral data were obtained from National Milk Records (Chippenham, UK), who collect large volumes of data continuously on a monthly basis. Two approaches were followed: using genetic algorithms for feature selection and network design (model 1), and transfer learning with a pretrained DenseNet model (model 2). Feature selection in model 1 showed that the number of wave points in MIR data could be reduced from 1,060 to 196 wave points. The trained model converged after 162 epochs with validation accuracy and loss of 0.89 and 0.18, respectively. Although the accuracy was sufficiently high, the loss (in terms of predicting only 2 labels) was considered too high and suggested that the model would not be robust enough to apply to industry. Model 2 was trained in 2 stages of 100 epochs each with spectral data converted to gray-scale images and resulted in accuracy and loss of 0.97 and 0.08, respectively. Inspection on inference data showed prediction sensitivity of 0.89, specificity of 0.86, and prediction accuracy of 0.88. Results indicate that milk MIR data contains features relating to pregnancy status and the underlying metabolic changes in dairy cows, and such features can be identified by means of deep learning. Prediction equations from trained models can be used to alert farmers of nonviable pregnancies as well as to verify conception dates.

Predicting bovine tuberculosis status of dairy cows from mid-infrared spectral data of milk using deep learning.

Bovine tuberculosis (bTB) is a zoonotic disease in cattle that is transmissible to humans, distributed worldwide, and considered endemic throughout much of England and Wales. Mid-infrared (MIR) analysis of milk is used routinely to predict fat and protein concentration, and is also a robust predictor of several other economically important traits including individual fatty acids and body energy. This study predicted bTB status of UK dairy cows using their MIR spectral profiles collected as part of routine milk recording. Bovine tuberculosis data were collected as part of the national bTB testing program for Scotland, England, and Wales; these data provided information from over 40,500 bTB herd breakdowns. Corresponding individual cow life-history data were also available and provided information on births, movements, and deaths of all cows in the study. Data relating to single intradermal comparative cervical tuberculin (SICCT) skin-test results, culture, slaughter status, and presence of lesions were combined to create a binary bTB phenotype labeled 0 to represent nonresponders (i.e., healthy cows) and 1 to represent responders (i.e., bTB-affected cows). Contemporaneous individual milk MIR spectral data were collected as part of monthly routine milk recording and matched to bTB status of individual animals on the single intradermal comparative cervical tuberculin test date (±15 d). Deep learning, a sub-branch of machine learning, was used to train artificial neural networks and develop a prediction pipeline for subsequent use in national herds as part of routine milk recording. Spectra were first converted to 53 × 20-pixel PNG images, then used to train a deep convolutional neural network. Deep convolutional neural networks resulted in a bTB prediction accuracy (i.e., the number of correct predictions divided by the total number of predictions) of 71% after training for 278 epochs. This was accompanied by both a low validation loss (0.71) and moderate sensitivity and specificity (0.79 and 0.65, respectively). To balance data in each class, additional training data were synthesized using the synthetic minority over sampling technique. Accuracy was further increased to 95% (after 295 epochs), with corresponding validation loss minimized (0.26), when synthesized data were included during training of the network. Sensitivity and specificity also saw a 1.22- and 1.45-fold increase to 0.96 and 0.94, respectively, when synthesized data were included during training. We believe this study to be the first of its kind to predict bTB status from milk MIR spectral data. We also believe it to be the first study to use milk MIR spectral data to predict a disease phenotype, and posit that the automated prediction of bTB status at routine milk recording could provide farmers with a robust tool that enables them to make early management decisions on potential reactor cows, and thus help slow the spread of bTB.

Use of the Threshold of Toxicological Concern (TTC) approach for deriving target values for drinking water contaminants.

Ongoing pollution and improving analytical techniques reveal more and more anthropogenic substances in drinking water sources, and incidentally in treated water as well. In fact, complete absence of any trace pollutant in treated drinking water is an illusion as current analytical techniques are capable of detecting very low concentrations. Most of the substances detected lack toxicity data to derive safe levels and have not yet been regulated. Although the concentrations in treated water usually do not have adverse health effects, their presence is still undesired because of customer perception. This leads to the question how sensitive analytical methods need to become for water quality screening, at what levels water suppliers need to take action and how effective treatment methods need to be designed to remove contaminants sufficiently. Therefore, in the Netherlands a clear and consistent approach called 'Drinking Water Quality for the 21st century (Q21)' has been developed within the joint research program of the drinking water companies. Target values for anthropogenic drinking water contaminants were derived by using the recently introduced Threshold of Toxicological Concern (TTC) approach. The target values for individual genotoxic and steroid endocrine chemicals were set at 0.01 µg/L. For all other organic chemicals the target values were set at 0.1 µg/L. The target value for the total sum of genotoxic chemicals, the total sum of steroid hormones and the total sum of all other organic compounds were set at 0.01, 0.01 and 1.0 µg/L, respectively. The Dutch Q21 approach is further supplemented by the standstill-principle and effect-directed testing. The approach is helpful in defining the goals and limits of future treatment process designs and of analytical methods to further improve and ensure the quality of drinking water, without going to unnecessary extents.

Superinduction of estrogen receptor mediated gene expression in luciferase based reporter gene assays is mediated by a post-transcriptional mechanism.

Several estrogenic compounds including the isoflavonoid genistein have been reported to induce a higher maximal response than the natural estrogen 17ß-estradiol in in vitro luciferase based reporter gene bioassays for testing estrogenicity. The phenomenon has been referred to as superinduction. The mechanism underlying this effect and thus also its biological relevance remain to be elucidated. In the present study several hypotheses for the possible mechanisms underlying this superinduction were investigated using genistein as the model compound. These hypotheses included (i) a non-estrogen receptor (ER)-mediated mechanism, (ii) a role for an ER activating genistein metabolite with higher ER inducing activity than genistein itself, and (iii) a post-transcriptional mechanism that is not biologically relevant but specific for the luciferase based reporter gene assays. The data presented in this study indicate that induction and also superinduction of the reporter gene is ER-mediated, and that superinduction by genistein could be ascribed to stabilization of the firefly luciferase reporter enzyme increasing the bioluminescent signal during the cell-based assay. This indicates that the phenomenon of superinduction may not be biologically relevant but may rather represent a post-transcriptional effect on enzyme stability.

Continuous flow 2H/1H and 18O/16O analysis of water samples with dual inlet precision.

A method for isotope ratio analysis of water samples is described comprising an on-line high-temperature reduction technique in a helium carrier gas. Using a gas-tight syringe, injection of 0.5 to 1 microL sample is made through a heated septum into a glassy carbon reactor at temperatures in excess of 1300 degrees C. More than 150 injections can be made per day and both isotope ratios of interest, delta2H and delta18O, can be measured with the same setup. The technique has the capability to transfer high-precision stable isotope ratio analysis of water samples from a specialized to a routine laboratory task compatible with other common techniques (automated injection for GC, LC, etc.). Experiments with an emphasis on the reactor design were made in two different laboratories using two different commercially available high-temperature elemental analyser (EA) systems. In the Jena TC/EA unit, sample-to-sample memory (single injection) has been reduced to approximately 1% and high precision of about 0.1 per thousand for delta18O and < 1 per thousand for delta2H has been achieved by a redesign of the glassy carbon reactor and by redirecting the gas flow of the commercial TC/EA unit. With the modified reactor, the contact of water vapour with surfaces other than glassy carbon is avoided completely. The carrier gas is introduced at the bottom of the reactor thereby flushing the outer tube compartment of the tube-in-tube assembly before entering the active heart of the reactor.With the Leipzig high-temperature reactor (HTP) similar precision was obtained with a minor modification (electropolishing) of the injector metal sleeve. With this system, the temperature dependence of the reaction has been studied between 1100 and 1450 degrees C. Complete yield and constant isotope ratio information has been observed only for temperatures above 1325 degrees C. For temperatures above 1300 degrees C the reactor produces an increasing amount of CO background from reaction of glass carbon with the ceramic tube. This limits the usable temperature to a maximum of 1450 degrees C. Relevant gas permeation through the Al2O3 walls has not been detected up to 1600 degrees C.

Extraction of CO2 from air samples for isotopic analysis and limits to ultra high precision delta18O determination in CO2 gas.

The determination of delta18O values in CO2 at a precision level of +/-0.02 per thousand (delta-notation) has always been a challenging, if not impossible, analytical task. Here, we demonstrate that beyond the usually assumed major cause of uncertainty - water contamination - there are other, hitherto underestimated sources of contamination and processes which can alter the oxygen isotope composition of CO2. Active surfaces in the preparation line with which CO2 comes into contact, as well as traces of air in the sample, can alter the apparent delta18O value both temporarily and permanently. We investigated the effects of different surface materials including electropolished stainless steel, Duran glass, gold and quartz, the latter both untreated and silanized. CO2 frozen with liquid nitrogen showed a transient alteration of the 18O/16O ratio on all surfaces tested. The time to recover from the alteration as well as the size of the alteration varied with surface type. Quartz that had been ultrasonically cleaned for several hours with high purity water (0.05 microS) exhibited the smallest effect on the measured oxygen isotopic composition of CO2 before and after freezing. However, quartz proved to be mechanically unstable with time when subjected to repeated large temperature changes during operation. After several days of operation the gas released from the freezing step contained progressively increasing trace amounts of O2 probably originating from inclusions within the quartz, which precludes the use of quartz for cryogenically trapping CO2. Stainless steel or gold proved to be suitable materials after proper pre-treatment. To ensure a high trapping efficiency of CO2 from a flow of gas, a cold trap design was chosen comprising a thin wall 1/4" outer tube and a 1/8" inner tube, made respectively from electropolished stainless steel and gold. Due to a considerable 18O specific isotope effect during the release of CO2 from the cold surface, the thawing time had to be as long as 20 min for high precision delta18O measurements. The presence of traces of air in almost all CO2 gases that we analyzed was another major source of error. Nitrogen and oxygen in the ion source of our mass spectrometer (MAT 252, Finnigan MAT, Bremen, Germany) give rise to the production of NO2 at the hot tungsten filament. NO2+ is isobaric with C16O18O+ (m/z 46) and interferes with the delta18O measurement. Trace amounts of air are present in CO2 extracted cryogenically from air at -196 degrees C. This air, trapped at the cold surface, cannot be pumped away quantitatively. The amount of air present depends on the surface structure and, hence, the alteration of the measured delta18O value varies with the surface conditions. For automated high precision measurement of the isotopic composition of CO2 of air samples stored in glass flasks an extraction interface ('BGC-AirTrap') was developed which allows 18 analyses (including standards) per day to be made. For our reference CO2-in-air, stored in high pressure cylinders, the long term (>9 months) single sample precision was 0.012 per thousand for delta13C and 0.019 per thousand for delta18O.

An interlaboratory study to test instrument performance of hydrogen dual-inlet isotope-ratio mass spectrometers.

An interlaboratory comparison of forty isotope-ratio mass spectrometers of different ages from several vendors has been performed to test 2H/1H performance with hydrogen gases of three different isotopic compositions. The isotope-ratio results (unsufficiently corrected for H3+ contribution to the m/z = 3 collector, uncorrected for valve leakage in the change-over valves, etc.) expressed relative to one of these three gases covered a wide range of values: -630% to -790% for the second gas and -368% to -462% for the third gas. After normalizing the isotopic abundances of these test gases (linearly adjusting the delta values so that the gases with the lowest and highest 2H content were identical for all laboratories), the standard deviation of the 40 measurements of the intermediate gas was a remarkably low 0.85%. It is concluded that the use of scaling factors is mandatory for providing accurate internationally comparable isotope-abundance values. Linear scaling for the isotope-ratio scales of gaseous hydrogen mass spectrometers is completely adequate.

Referencing strategies and techniques in stable isotope ratio analysis.

Stable isotope ratios are reported in the literature in terms of a deviation from an international standard (delta-values). The referencing procedures, however, differ from instrument to instrument and are not consistent between measurement facilities. This paper reviews an attempt to unify the strategy for referencing isotopic measurements. In particular, emphasis is given to the importance of identical treatment of sample and reference material ('IT principle'), which should guide all isotope ratio determinations and evaluations. The implementation of the principle in our laboratory, the monitoring of our measurement quality, the status of the international scales and reference materials and necessary correction procedures are discussed.

The position dependent 15N enrichment of nitrous oxide in the stratosphere.

The position dependent 15N fractionation of nitrous oxide (N2O), which cannot be obtained from mass spectrometric analysis on molecular N2O itself, can be determined with high precision using isotope ratio mass spectrometry on the NO+ fragment that is formed on electron impact in the source of an isotope ratio mass spectrometer. Laboratory UV photolysis experiments show that strong position dependent 15N fractionations occur in the photolysis of N2O in the stratosphere, its major atmospheric sink. Measurements on the isotopic composition of stratospheric N2O indeed confirm the presence of strong isotope enrichments, in particular the difference in the fractionation constants for 15N14NO and 14N15NO. The absolute magnitudes of the fractionation constants found in the stratosphere are much smaller, however, than those found in the lab experiments, demonstrating the importance of dynamical and also additional chemical processes like the reaction of N2O with O(1D).

Stable-Isotope Analysis of a Combined Nitrification-Denitrification Sustained by Thermophilic Methanotrophs under Low-Oxygen Conditions.

To simulate growth conditions experienced by microbiota at O(inf2)-limited interfaces of organic matter in compost, an experimental system capable of maintaining dual limitations of oxygen and carbon for extended periods, i.e., a pO(inf2)-auxostat, has been used. (sup15)N tracer studies on thermophilic (53(deg)C) decomposition processes occurring in manure-straw aggregates showed the emission of dinitrogen gas from the reactor as a result of simultaneous nitrification and denitrification at low pO(inf2) values (0.1 to 2.0%, vol/vol). The N loss was confirmed by nitrogen budget studies of the system. Depending on the imposed pO(inf2), 0.6 to 1.4 mmol of N/day (i.e., 20 to 40% of input N) was emitted as N(inf2). When the pO(inf2) was raised, the rates of both nitrification and denitrification increased instantaneously, indicating that ammonia oxidation was limited by oxygen. In auxostats permanently running at pO(inf2) >= 2% (vol/vol), the free ammonium pool was almost completely oxidized and was converted to nitrite plus nitrate and N(inf2) gas. Labelling of the auxostat with [(sup13)C]carbonate was conducted to reveal whether nitrification was of autotrophic or heterotrophic origin. Incorporation of (sup13)CO(inf2) into population-specific cellular compounds was evaluated by profiling the saponifiable phospholipid fatty acids (FAs) by using capillary gas chromatography and subsequently analyzing the (sup13)C/(sup12)C ratios of the individual FAs, after their combustion to CO(inf2), by isotope ratio mass spectrometry. Apart from the observed label incorporation into FAs originating from a microflora belonging to the genus Methylococcus (type X group), supporting nitrification of a methylotrophic nature, this analysis also corroborated the absence of truly autotrophic nitrifying populations. Nevertheless, the extent to which ammonia oxidation continued to exist in this thermophilic community suggested that a major energy gain could be associated with it.

Gestational trophoblastic disease metastatic to the brain.

PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).

Management of early-stage Hodgkin's lymphoma. The radiation oncology experience at Northwestern University/Northwestern Memorial Hospital.

Early-stage Hodgkin's lymphoma patients treated with radiotherapy alone or combined modality therapy were retrospectively analyzed for survival, patterns of failure, salvage, and toxicity. Of 75 evaluable patients, 47 were given radiotherapy alone and 28 were given combination radiotherapy and chemotherapy. Of the patients studied, 26 were clinical stage I and 49 were clinical stage II, with nine patients upstaged at laparotomy. Minimum follow-up was 2 years, with a median of 81 months. Complete response rate was 95%. Relapse-free survival and overall survival were 89% and 96%, respectively, at 2 years; 78% and 86% at 5 years; and 76% and 82% at 10 years. Of 16 patients who relapsed (21%), 13/47 patients were treated with radiotherapy and 3/28 were treated with combined modality therapy. Salvage rates were higher in those treated with radiotherapy alone. There were 13 deaths: six from disease, two from treatment-related complications, and five from second primary malignancies. There was a higher incidence of second malignancies and deaths due to complication in patients treated with combined modality therapy. Radiotherapy alone or with chemotherapy is an effective modality in the treatment of Hodgkin's lymphoma. Treatment should be selected properly to optimize results and decrease complications.

High precision isotope ratio monitoring techniques in mass spectrometry.

Isotope ratio monitoring following on-line combustion is a new method in gas chromatography/mass spectrometry (GC/MS) that allows the ratios of abundances of stable isotopes of elements such as carbon and nitrogen to be determined for individual compounds introduced via a gas chromatograph. It is the first combustion method that allows direct measurement of isotope ratios of individual molecular components of mixtures. Unlike traditional gas isotope ratio measurements made on pure samples, the method requires only very small samples, viz. several picolitres of the vapour. This paper reviews the principles and history of gas isotope ratio monitoring, focusing on the instrumentation used in isotope ratio monitoring GC/MS, including the combustion procedures used for atomization. Standardization methods and data manipulation techniques are described, as are applications to geochemistry, biology, medicine and other areas of science.

Hyperfractionated craniospinal radiation in medulloblastoma.

From 1986 to 1991, 13 patients at Northwestern Memorial Hospital were entered onto a pilot study designed to test the feasibility of treating children with medulloblastoma (11 patients) or primitive neuroectodermal tumors of the cerebral hemispheres (2 patients) with hyperfractionated craniospinal radiotherapy (HFxRT). Follow-up times ranged from 10 to 96 months with a median of 53 months. The patients were prospectively divided among three treatment arms depending on prior treatment history, if any, and degree of surgical resection. The 3 patients in group I had undergone gross total resection of the primary site, receiving 64.8 Gy to the primary site and 31.2 Gy directed to the craniospinal axis (CSA). Of these 3 patients, patient 1 had residual disease in the thoracic spine at T-10. The 8 patients in group II, who had gross residual disease remaining at the primary site, received 72 Gy to the primary site and 34 Gy to the CSA. Five of these eight patients in group II also received 8-in-1 chemotherapy. The 2 patients in group III had already failed chemotherapy and were then treated with 60 Gy to the primary site and 26 Gy to the CSA. Of the 11 patients in groups I and II, 7 of the 11 (64%) have never recurred. Two of the three group-I patients have not recurred, and 5 of the 7 group-II patients have not recurred. In addition, patient 7 (group II) remains alive after salvage with bone marrow transplant, following a local failure bordering the tentorium. Unfortunately, neither of the group-III patients could be salvaged with HFxRT. Acute/subacute toxicities included 7 cases of external auditory canal or skin desquamation, 2 cases of postradiation somnolence, and 1 case each of poor wound healing and neutropenia. Chronic toxicities included hypothyroidism in 2 patients and growth problems in 2 patients. Neuropsychologic complications affected only the 3 youngest patients in the study. Three patients developed neurologic sequelae attributed to radiation, including 1 with progressive urinary incontinence, 1 who developed a transient ischemic attack, and 1 who became progressively ataxic. Our research, although based on a small number of patients, suggests that hyperfractionated radiation therapy to craniospinal access is feasible and that the survival results are favorable. This treatment strategy should be further explored in a phase-III randomized trial.

Microcombustion of ng Amounts of Carbon in Non-Volatile Materials for isotope Ratio Evaluation.

Abstract A novel microcombustion technique for carbon isotopic analysis of nanogram amounts of carbon in non-volatile materials based on isotope ratio monitoring (irm) mass spectrometry is described. Liquid or solid samples placed in a quartz sleeve are combusted at 1000°C in a continuous stream of helium and oxygen. CO(2) removed from the carrier gas stream by cryogenic trapping is transferred onto a GC column. Following GC separation, the CO(2) is transferred via an open split to the ion source of a gas isotope ratio mass spectrometer. Reproducibility for samples >25 nmol carbon is <1‰. Problems associated with blanks from various sources and with reproducible deposition of small sample amounts led to variable accuracy, which was dependent on the compound class being analysed. Minimum sample size was in the range from 5 to 10 nmol carbon. Measurements of dissolved organic carbon (DOC) of groundwater from Germany yielded consistent values of δ(13)C = -28.8‰.

New methods for fully automated isotope ratio determination from hydrogen at the natural abundance level.

Abstract A variety of methods for measurement of (2)H/(1)H from H(2) are evaluated for their ability to be fully automated and for applicability to automated isotopic analysis of water and organic compounds. Equilibration of water with H(2) gas with the aid of a platinum catalyst has been commercialized into a fully automated sample preparation device. A second and newer technique, involving injecting water, methane, or other volatile organic compounds onto hot chromium in a reactor attached to the dual inlet system of a gas isotope ratio mass spectrometer, can be integrated with a conventional GC-autosampler to allow automated analysis of a variety of substrates. Both techniques result in precisions around 1‰ (δ notation) on the VSMOW scale, and are fast and accurate, and with appropriate mass spectrometers require only negligible scaling for the SLAP/VSMOW difference. Several experimental methods which show considerable promise employ "isotope ratio monitoring" (irm) inlet systems, in which a carrier gas is used for transport of H(2) to the mass spectrometer. Any such method has to address the problem of He ions corrupting the measurement of the H(2) ions. One such approach uses a heated palladium membrane for selective introduction of H(2) into the mass spectrometer, and a second involves modifications to the ion optics to control the stray helium ions. Both approaches have significant limitations that must be overcome before irm techniques can be used in routine applications, in particular for measuring hydrogen isotopes from GC effluents (irm-GCMS).

Isotope-Ratio-Monitoring Liquid Chromatography Mass Spectrometry (IRM-LCMS): First Results from a Moving Wire Interface System.

Abstract A Liquid Chromatography-Combustion (LC-C) Interface, based on a moving wire technique, has been built and tested. The LC effluent is deposited onto a transport wire, which carries the sample through solvent evaporation and combustion ovens. CO(2) from the combustion step is analysed in an isotope ratio mass spectrometer. Performance of the interface was tested by loop injections of sucrose and glucose into a liquid flow of methanol/water (80/20). Accuracy and precision of δ(13)C(PDB) < 1‰ was achieved for sample concentrations > 500 ng/ul (5µl loop), sufficient for studies at natural isotope ratios. In case of (13)C tracer applications the detection limit was determined to be about 20 pg carbon tracer (on wire).

[Ambulatory rehabilitation--usefulness and cost savings]. / Ambulante Rehabilitationen--Nutzen und Kostenersparnis.

All these data suggested, that rehabilitation can be more quickly effected and may have a better outcome using the EAP, than has been achieved with traditional therapies. Because the treatment is so new, it will be some time before the data become statistically significant. It is expected that confirm development of EAP may in the future lead to still better outcomes. Ambulatory rehabilitation is only available at large center, making the necessary daily units difficult for patients who live in outlying areas.