Continuous wave terahertz systems exploiting 1.5 microm telecom technologies.

A fiber-assembled CW THz System operating at 1.5 microm is presented. High speed telecom photodiodes integrated with planar THz antennas serve as THz emitters with power up to 10 microW. Photoconductive antennas based on LT InGaAs/InAlAs multi-layer structures allow coherent detection. The system operates in a wide frequency range of 0.1 -1.6 THz.

The influence of diffuse pollution on groundwater content patterns for the groundwater bodies of Germany.

Commissioned by Germany's Working Group of the Federal States on Water Problems (LAWA) the authors developed a procedure to define natural groundwater conditions from groundwater monitoring data. The distribution pattern of a specific groundwater parameter observed by a number of groundwater monitoring stations within a petrographically comparable groundwater typology is reproduced by two statistical distribution functions, representing the "natural" and "influenced" component. The range of natural groundwater concentrations is characterized by confidence intervals of the distribution function of the natural component. The applicability of the approach was established for 17 hydrochemical different groundwater typologies occurring throughout Germany. Based on groundwater monitoring data from ca. 26,000 groundwater-monitoring stations, 40 different hydrochemical parameters were evaluated for each groundwater typology. For all investigated parameters the range of natural groundwater concentrations has been identified. According to the requirements of the EC Water Framework Directive (article 17) (WFD) this study is a basis for the German position to propose criteria for assessing a reference state for a "good groundwater chemical status".

Area-differentiated modelling of P-fluxes in heterogeneous macroscale river basins.

A model (MEPhos) for the calculation of the total phosphorus output from diffuse sources by drainage, wash-off, groundwater outflow, soil erosion and rainwater sewers as well as from point sources is presented. The model is based on a pathway- and area-differentiated emissions approach and calculates mean long-term P-inputs to surface waters. Phosphotopes are used for spatial discretization and modelling of diffuse P-inputs. Based on the modelling results "hot spots" for high P-loads can be localized and a management option for the input reduction to surface waters can be proposed which are adapted to site properties. The applicability of the model is demonstrated for two macroscale river basins in Germany (- 13,000 km(2) each) with contrasting natural conditions and land use patterns.

Water fluxes and diffuse nitrate pollution at river basin scale: coupling of agro-economic models and hydrological approaches.

An integrated model system has been developed to estimate the impact of nitrogen reduction measures on the nitrogen load in groundwater and in river catchment areas. The focus lies on an area-wide, regionally differentiated, consistent link-up between the indicator "nitrogen balance surplus" and nitrogen charges into surface waters. As a starting point of the analysis actual nitrogen surpluses in the soil were quantified using the agro-economic RAUMIS-model, which considers the most important N-inputs to the soil and N-removals from the soil through crop harvest. The most important pathways for diffuse nitrogen inputs into river systems are modelled with the water balance model GROWA. Additionally, the time-dependent nitrogen degradation along the nitrogen pathways in soil and groundwater are modelled using the WEKU-model. The two selected river basins in Germany cover a variety of landscape units with different hydrological, hydrogeological and socio-economic characteristics. The results indicate a wide range of annual nitrogen surpluses for the rural areas between than 10 kg N ha(-1) x a(-1) and 200 kg N ha(-1) x a(-1) or more, depending on the type and intensity of farming. The level of nitrogen inputs into the surface waters is reduced because of degradation processes during transport in soil and groundwater. Policy impact analyses for a nitrogen tax and a limitation of the livestock density stress the importance of regionally adjusted measures.

A procedure to define natural groundwater conditions of groundwater bodies in Germany.

Commissioned by Germany's Working Group of the Federal States on Water Problems (LAWA) the authors developed a procedure to define natural groundwater conditions from groundwater monitoring data. The distribution pattern of a specific groundwater parameter observed by a number of groundwater monitoring stations within a petrographically comparable groundwater typology is reproduced by two statistical distribution functions, representing the "natural" and "influenced" components. The range of natural groundwater concentrations is characterized by confidence intervals of the distribution function of the natural component. The applicability of the approach was established for four hydrochemically different groundwater typologies occurring throughout Germany. Based on groundwater monitoring data from 7920 groundwater monitoring stations, 15 different hydrochemical parameters were evaluated for each groundwater typology. For all investigated parameters the range of natural groundwater concentrations has been identified. According to the requirements of the EC Water Framework Directive (article 17) (WFD) this study is a basis for the German position to propose criteria for assessing a reference state for a "good groundwater chemical status".

Management of regional German river catchments (REGFLUD) impact of nitrogen reduction measures on the nitrogen load in the River Ems and the River Rhine.

The REGFLUD-project, commissioned by Germany's Federal Research Ministry (BMBF), addresses the problem of reducing diffuse pollution from agricultural production. The objective of the project is the development and application of multi-criteria scientific methods, which are able to predict diffuse pollution in river basins subject to economic feasibility and social acceptability. The selected river basins (Ems and Rhine basins) cover a variety of landscape units with different hydrological, hydrogeological and socio-economic characteristics. This paper focuses on the analysis of the effects of certain policy measures to reduce diffuse pollution by nitrogen. For this purpose a model system consisting of an agricultural sector model, a water balance model and a residence time/denitrification model was developed and applied. First results indicate a wide range of annual nitrogen surpluses for the rural areas between less than 10 kg N/ha up to 200 kg N/ha or more depending on the type and intensity of farming. Compared to the level of nitrogen surpluses the level of nitrogen inputs into the surface waters is relatively moderate because of degradation processes during transport in soil and groundwater. Policy impact analysis for a nitrogen tax and a limitation of the livestock density stress the importance of regionally tailored measures.

Groundwater-borne nitrate intakes into surface waters in Germany.

The nitrogen loads entering the surface waters in Germany via the groundwater path were quantified. For this purpose, the results of a nitrogen balance model (Bach et al., 2000), which considers the most important N-inputs to the soil (manure, inorganic fertiliser, atmospheric deposition) and N-removals from the soil through crop harvest, were combined with the groundwater residence time/denitrification model WEKU (Kunkel and Wendland, 1997; Wendland et al., 2001). The modelled groundwater-borne nitrogen inputs into surface waters were validated using results from the MONERIS model (Behrendt et al., 2000) concerning riverine nitrogen retention, nitrogen inputs from point sources as well as nitrogen inputs through direct run-off (drainage etc.). In the vicinity of surface waters and in solid rock areas, the groundwater borne nitrogen inputs into surface waters are considerably high compared to the inputs into the aquifer due to predominantly unfavourable de-nitrification conditions and short residence times of groundwater. In the North German lowlands, however, the groundwater-borne nitrate inputs into surface waters are considerably low compared to the inputs into the aquifer. There, the residence time of groundwater in the aquifer is high and the groundwater is predominantly oxygen free and contains pyrite and/or organic carbon compounds, allowing a halving of the nitrate loads in the groundwater within a period of 1 to 4 years (see Wendland and Kunkel, 1999).

The SOIL-N/WEKU model system--a GIS-supported tool for the assessment and management of diffuse nitrogen leaching at the scale of river basins.

The SOIL-N/WEKU model system was developed to estimate groundwater-borne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out in the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) for a macroscale study river basin in Germany (the Uecker basin, ca. 2,400 km2) and a mesoscale study catchment area in Denmark (the Gjern basin, ca. 200 km2). For both catchment areas, the modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwater-borne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparison with observed groundwater-borne riverine nitrogen loads showed a very good agreement, proving the key role nitrogen retention in groundwater plays in the two catchment areas.

Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates.

OBJECTIVE: To determine if prophylactic administration of C1-esterase-inhibitor would have a beneficial effect on postoperative weight gain and the inflammatory response in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Twenty-four neonates with transposition of the great arteries. INTERVENTIONS: In group inhibitor (INH) patients (n = 12), 100 IU/kg of C1-esterase-inhibitor (Berinert) was given 30 minutes before CPB. In group placebo (P) patients (n = 12), placebo was administered instead. Interleukin (IL)-6, C3a anaphylatoxin, C1 activity, prekallikrein, Hageman factor, D-dimers, and clinical parameters were measured 6 times perioperatively. MEASUREMENTS AND MAIN RESULTS: All 24 patients had an uneventful clinical course. Mean arterial pressure and pulmonary oxygenation after CPB were superior in group INH patients. The weight gain on postoperative days 1 to 4 was significantly less in group INH patients compared with group P (55 +/- 59 g vs. 340 +/- 121 g, day 1). The concentration of IL-6 (76 +/- 17 pg/mL vs. 262 +/- 95 pg/mL during CPB) was significantly lower in group INH patients compared with group P patients. In contrast, no influence on C3a anaphylatoxin and coagulation factors was found. CONCLUSION: Prophylactic application of C1-esterase-inhibitor in neonates undergoing arterial switch operations produces less inflammatory response compared with placebo. This difference may have contributed to improved clinical parameters, including less weight gain postoperatively.

Model system for the management of nitrogen leaching at the scale of river basins and regions.

In the framework of the EU-project RANR (Regional analysis of subsurface nitrogen retention and its impact on the nitrogen export from land to sea) a model system was developed to estimate groundwaterborne nitrogen inputs into river systems. The core of this model system is composed of a soil nitrogen leaching model (SOIL-N) and a groundwater residence time/denitrification model (WEKU). The application of the model system was carried out for the study catchment areas of the Uecker basin (ca. 2400 km2, Germany) and the Gjern basin (ca. 200 km2, Denmark). For both catchment areas, the modelled average nitrogen loads leached into the groundwater were about 40 kg N/ha a, while the remaining groundwaterborne nitrogen intake to rivers was quantified to an average of about 2 kg/ha a. The comparision with observed groundwaterborne riverine nitrogen loads showed a very good agreement, proofing the key role nitrogen retention in groundwater plays in the two catchment areas. With regard to the generalisation and transfer of the SOIL-N/WEKU model concept we assume that the model can be applicated in catchment areas in the European Pleistocene Lowland, which ranges from the Netherlands in the west to the Baltic States and the Ukraine in the east.

Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents.

Dendritic cells (DCs) can efficiently acquire foreign antigen(s) from apoptotic cells and induce MHC class I-restricted, antigen-specific CTLs. An accumulation of DCs within solid tumor masses in situ has been associated indirectly with a more favorable prognosis. Therefore, DCs may offer an efficient means for triggering immune responses within tumors, particularly in those masses containing significant apoptosis. We examined whether delivery of DCs could, alone, impact on the progressive growth of a tumor with a relatively high apoptotic index. We detected significant early apoptosis within the mass of a s.c. growing murine MT-901 breast carcinoma. DCs could efficiently engulf MT-901 tumor apoptotic cells in vitro. Intratumoral injections of syngeneic but not allogeneic DCs resulted in significant inhibition of MT-901 tumor growth. Histological examination of the tumor revealed intense mononuclear cell infiltration during and after DC injections. Tumor growth inhibition was relatively radiosensitive and dependent on host-derived CD8+ T cells. The baseline level of tumor apoptosis could be increased substantially by tumor necrosis factor alpha administration, leading to a greater DC-mediated antitumor effect. The antitumor effect could also be enhanced by first pulsing DCs with the foreign helper protein, keyhole limpet hemocyanin, prior to intratumoral delivery and combining it with the systemic administration of interleukin 2. Splenocytes from treated animals showed heightened levels of specific CTL activity and production of cytokines. The level of in situ tumor apoptosis appears to play a critical role in DC-mediated antitumor effects. The potential implication of these findings in DC-based tumor therapy strategies is discussed.

Role of C5a in multiorgan failure during sepsis.

In humans with sepsis, the onset of multiorgan failure (MOF), especially involving liver, lungs, and kidneys, is a well known complication that is associated with a high mortality rate. Our previous studies with the cecal ligation/puncture (CLP) model of sepsis in rats have revealed a C5a-induced defect in the respiratory burst of neutrophils. In the current CLP studies, MOF occurred during the first 48 h with development of liver dysfunction and pulmonary dysfunction (falling arterial partial pressure of O(2), rising partial pressure of CO(2)). In this model an early respiratory alkalosis developed, followed by a metabolic acidosis with increased levels of blood lactate. During these events, blood neutrophils lost their chemotactic responsiveness both to C5a and to the bacterial chemotaxin, fMLP. Neutrophil dysfunction was associated with virtually complete loss in binding of C5a, but binding of fMLP remained normal. If CLP animals were treated with anti-C5a, indicators of MOF and lactate acidosis were greatly attenuated. Under the same conditions, C5a binding to blood neutrophils remained intact; in tandem, in vitro chemotactic responses to C5a and fMLP were retained. These data suggest that, in the CLP model of sepsis, treatment with anti-C5a prevents development of MOF and the accompanying onset of blood neutrophil dysfunction. This may explain the protective effects of anti-C5a in the CLP model of sepsis.

Clinical manifestations of migraine.

Migraine is a disorder with many clinical manifestations that vary from person to person and often from headache to headache in the same person. Several body organ systems are involved in a migraine attack. It is a condition that is underdiagnosed by physicians and misidentified by persons suffering with headaches. Many individuals with migraine self-diagnose as having sinus headaches or tension headaches. This article discusses the many symptoms of migraine and will help the busy practitioner to better recognize and diagnose this common disorder.

Survey of migraineurs referred to headache specialists: care, satisfaction, and outcomes.

The authors report a survey of 281 migraineurs recently referred to headache specialists by primary care physicians. Compared with care before referral, specialists spent substantially more time with patients and were more likely to ask patients to take a prophylactic drug and to keep a headache diary, to discuss migraine triggers, and to prescribe 5-hydroxytryptamine1B/1D agonists (triptans). After referral, patients reported improved satisfaction with care and significant decreases in frequency, duration, and severity of attacks.

Impact of headache education program in the workplace.

We evaluated the impact of a headache education program in a workplace setting. A 45-minute standardized educational program was delivered to 492 participants at eight companies. Participants completed questionnaires regarding their headaches and headache management techniques, the Short Form (SF)-36, and the Headache Disability Inventory (HDI) before and 1 month after the presentation. The intervention significantly improved health-related quality of life, decreased headache-related disability, and promoted the use of self-management techniques.

Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo.

In the present paper, we characterize an antibody, mAb BV13, directed to mouse vascular endothelial (VE)-cadherin, a major adhesive protein of interendothelial adherens junctions. When added to cultured endothelial cells, BV13 induces a redistribution of VE-cadherin from intercellular junctions. VE-cadherin redistribution did not change the localization of platelet endothelial cell adhesion molecule or tight junction markers such as zonula occludens 1, cingulin, and junctional adhesion molecule. Intravenous administration of mAb BV13 induced a concentration- and time-dependent increase in vascular permeability in heart and lungs. By electron microscopy, interstitial edema and accumulation of mixed types of inflammatory cells in heart and lungs were observed. Injection of (rhodamine-labeled) Ricinus communis I lectin showed focal spots of exposed basement membrane in the alveolar capillaries and in some larger pulmonary vessels. These data indicate that VE-cadherin is required for vascular integrity and normal organ functions.

Recruitment of non-patient volunteers with schizophrenia spectrum personality symptoms.

Authors aimed to evaluate the yield and effectiveness of recruiting community schizophrenia spectrum personality (SSP) subjects via targeted newspaper advertisements listing SSP traits. Eight newspaper advertisements listing SSP traits were placed in regional newspapers over a 3-year period. Respondents (n = 209) were screened thoroughly via telephone, and eligible subjects were invited for face-to-face clinical interviews. One hundred and one subjects (48% of the respondents) were screened out over the phone and another 30% were no-shows or refused. Of the 46 subjects who were interviewed, a majority (24 subjects; 52%) met this study's criteria for SSP. These subjects experienced significant psychotic-like symptoms, as ascertained by a self-rating scale, and showed a downward drift in their socio-economic status. One can successfully recruit SSP subjects, with high yield, using targeted telephone advertisements combined with thorough telephone screening.

Podocyte phenotypes as defined by expression and distribution of GLEPP1 in the developing glomerulus and in nephrotic glomeruli from MCD, CNF, and FSGS. A dedifferentiation hypothesis for the nephrotic syndrome.

Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell (VGEC) foot processes. Double label immunofluorescence, immunoelectron microscopy, and peroxidase immunohistochemistry were used to map the GLEPP1 distribution in the developing glomerulus and in minimal-change nephropathy (MCN), congenital nephrotic syndrome of the Finnish type, and focal-segmental glomerulosclerosis (FSGS). In MCN GLEPP1 was shifted away from the glomerular basement membrane on the apical cell membrane of effaced foot processes. These data are compatible with the previously suggested concept that MCN can be considered a form of dedifferentiation of the podocyte phenotype. Similarly, changes seen in congenital nephrotic syndrome of the Finnish type can be considered a consequence of failure to complete normal podocyte development. In FSGS glomeruli GLEPP1 was frequently absent from VGECs, even when no sclerosis was detectable in that glomerulus. Therefore, in FSGS, VGECs may lose GLEPP1, and this loss appears to occur in the absence of scarring and may, therefore, precede the scarring process. We speculate that a changed VGEC phenotype that does not express GLEPP1 might have properties similar to the early undifferentiated VGEC developmental phenotype. GLEPP1 distribution pattern and absence from glomeruli of individuals with nephrotic syndrome may, therefore, represent a useful phenotypic marker.

Dosing of oral sumatriptan: a review of our first 104 patients.

BACKGROUND: The introduction of oral sumatriptan in the United States at doses of 25 and 50 mg, compared with 100-mg tablets worldwide, has created the need to develop a protocol for appropriate dosing. METHODS: We evaluated the first 104 patients in our practice to treat two migraine attacks with oral sumatriptan. For their first treatment with oral sumatriptan, patients were evaluated on their response to 25-mg tablets and the total number of tablets taken. For their second treatment, patients were evaluated on their response to sumatriptan, number of 25-mg tablets taken, and dosage prescribed for future migraines. RESULTS: [table see text] After the second treatment, 41 patients (40%) continued therapy with 25-mg tablets, 54 (53%) were prescribed 50-mg tablets, 2 patients (2%) were prescribed two 50-mg tablets, and 5 patients (5%) were prescribed injectable sumatriptan. Seventy patients had previously used injectable sumatriptan, while 34 had not previously used sumatriptan. There were no significant differences in their response to oral sumatriptan. CONCLUSION: Oral sumatriptan was effective in clinical practice at doses of 25 and 50 mg. The majority of patients required more than one 25-mg tablet for a migraine attack, reflecting both inadequacy of dosing for some migraines and recurrence of headache, yet 40% of patients continued on treatment with 25-mg tablets. There were no significant differences in response to therapy in patients being switched from injectable to oral sumatriptan compared with those initiating therapy with oral sumatriptan. Both tablet strengths of oral sumatriptan are useful in clinical practice.

Spontaneous dyskinesia in subjects with schizophrenia spectrum personality.

OBJECTIVE: The study of spontaneous dyskinesia in schizophrenia is confounded by the widespread use of neuroleptics. The authors hypothesized that spontaneous dyskinesia would be present in subjects with schizophrenia spectrum personality (schizoid, paranoid, or schizotypal). They also tested the hypothesis that dyskinetic-like movements would increase after repeated dextroamphetamine challenge to the dopaminergic system. METHOD: Dyskinetic-like movements were assessed in 34 spectrum subjects and 22 normal subjects; nine subjects from each group were administered both placebo and repeated dextroamphetamine challenges. RESULTS: Spectrum subjects had more dyskinetic-like movements than normal subjects. Spontaneous dyskinesia was present in 12% of the spectrum subjects but was not seen in the normal subjects. Subjects with schizotypal personality had more dyskinetic-like movements than subjects with schizoid personality or normal subjects. Dyskinesia was present in 24% of the schizotypal subjects but not in the other groups. Dyskinetic movement scores correlated with positive symptom scores. With repeated amphetamine challenge, normal subjects showed a pattern of behavioral sensitization (an increase in dyskinetic-like movements), but spectrum subjects showed an abnormal response (fewer dyskinetic-like movements). CONCLUSIONS: Dyskinesia and dyskinetic-like movements are more common in subjects with schizophrenia spectrum personality (primarily schizotypal) than in normal subjects and are related to positive symptoms. A failure of normal behavioral sensitization mechanisms after dextroamphetamine challenge is seen in subjects with schizophrenia spectrum personality.