Stable charged cosmic strings.

We study the quantum stabilization of a cosmic string by a heavy fermion doublet in a reduced version of the standard model. We show that charged strings, obtained by populating fermionic bound state levels, become stable if the electroweak bosons are coupled to a fermion that is less than twice as heavy as the top quark. This result suggests that extraordinarily large fermion masses or unrealistic couplings are not required to bind a cosmic string in the standard model. Numerically we find the most favorable string profile to be a simple trough in the Higgs vacuum expectation value of radius ≈10(-18) m. The vacuum remains stable in our model, because neutral strings are not energetically favored.

Elevated CO2 effects on canopy and soil water flux parameters measured using a large chamber in crops grown with free-air CO2 enrichment.

An arable crop rotation (winter barley-sugar beet-winter wheat) was exposed to elevated atmospheric CO(2) concentrations ([CO(2) ]) using a FACE facility (Free-Air CO(2) Enrichment) during two rotation periods. The atmospheric [CO(2) ] of the treatment plots was elevated to 550 ppm during daylight hours (T>5°C). Canopy transpiration (E(C) ) and conductance (G(C) ) were measured at selected intervals (>10% of total growing season) using a dynamic CO(2) /H(2) O chamber measuring system. Plant available soil water content (gravimetry and TDR probes) and canopy microclimate conditions were recorded in parallel. Averaged across both growing seasons, elevated [CO(2) ] reduced E(C) by 9%, 18% and 12%, and G(C) by 9%, 17% and 12% in barley, sugar beet and wheat, respectively. Both global radiation (Rg) and vapour pressure deficit (VPD) were the main driving forces of E(C) , whereas G(C) was mostly related to Rg. The responses of E(C) and especially G(C) to [CO(2) ] enrichment were insensitive to weather conditions and leaf area index. However, differences in LAI between plots counteracted the [CO(2) ] impact on E(C) and thus, at least in part, explained the variability of seasonal [CO(2) ] responses between crops and years. As a consequence of lower transpirational canopy water loss, [CO(2) ] enrichment increased plant available soil water content in the course of the season by ca. 15 mm. This was true for all crops and years. Lower transpirational cooling due to a [CO(2) ]-induced reduction of E(C) increased canopy surface and air temperature by up to 2 °C and 0.5 °C, respectively. This is the first study to address effects of FACE on both water fluxes at canopy scale and water status of a European crop rotation.

Canopy CO2 exchange of sugar beet under different CO2 concentrations and nitrogen supply: results from a free-air CO2 enrichment study.

Sugar beet (Beta vulgaris ssp. altissima Döll) was grown in the field under free-air CO(2) enrichment (FACE, 550 ppm) and different nitrogen (N) supply (2001: 126 (N100) and 63 kg.ha(-1) (N50); 2004: 156 (N100) and 75 kg.ha(-1)) during two crop rotations. Canopy CO(2) exchange rates (CCER) were measured during the main growth phase (leaf area index > or =2) using a dynamic chamber system. Canopy CO(2) exchange data were analysed with respect to treatment effects on seasonal means and light use efficiency and light response characteristics. CO(2) enrichment enhanced CCER throughout the season. However, in both years, CCER declined after the second half of August independent of radiation and [CO(2)]. Elevated [CO(2)] strongly stimulated CCER on a seasonal basis, whereas the reduction of CCER caused by low N was below 10% and not significant. There were no effects of N on daily radiation use efficiency of carbon gain calculated from CCER data, but a strong enhancement by CO(2) enrichment. CCER closely tracked diurnal variations in incident photosynthetic photon flux density (PPFD, mumol.m(-2).s(-1)). The relationship between CCER and incident PPFD was curvilinear. In both seasons, initial slopes and maximum rates (CCER(max)) were determined from two 6-day periods using these relationships. The first period was measured after canopy closure (first half of July) and the second in the second half of August. In the first period, elevated [CO(2)] increased the initial slopes. Low N supply affected neither the initial slopes nor their response to elevated [CO(2)] in either period. In contrast to initial slopes, N stress limited the [CO(2)] response of CCER(max) in the first period. In the second period, however, this interaction of [CO(2)] and N on CCER(max) was completely dominated by a general decline of CCER(max) whereas no general decline of the initial slopes occurred in the second period. This response of light response parameters to [CO(2)] and N suggests that, in sugar beet, the decline of CCER in the late season may rely on limiting mechanisms such as photosynthetic acclimation responses to elevated [CO(2)] caused by sink limitations.

Growth and nutritive quality of Poa pratensis as influenced by ozone and competition.

Interspecific plant competition has been hypothesized to alter effects of early-season ozone (O3) stress. A phytometer-based approach was utilized to investigate O3 effects on growth and nutritive quality of Poa pratensis grown in monoculture and in mixed cultures with four competitor-plant species (Anthoxanthum odoratum, Achillea millefolium, Rumex acetosa and Veronica chamaedrys). Mesocosms were exposed during April/May 2000-2002 to charcoal-filtered air+25 ppb O3 (control) or non-filtered air+50 ppb O3 (elevated O3). Biomass production was not affected by O3, but foliar injury symptoms were observed in May 2002. Early-season O3 exposure decreased relative food value of P. pratensis by an average of 8%, which is sufficient to have nutritional implications for its utilization by herbivores. However, forage quality response to O3 was not changed by interspecific competition. Lack of injury and nutritive quality response in P. pratensis harvested in September may reflect recovery from early-season O3 exposure.

Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression.

Patients who have not received previous antiretroviral treatment (ART) have a high failure rate on the combination treatment of abacavir, lamivudine, and tenovir. We assessed the virological failure rate in eight patients with HIV-1 who switched to this combination after having complete virological suppression from their previous long-term ART (median 8.0 months, range 7.5-18.0). Five of the eight patients showed virological failure. Four of these five patients had either the K65R mutation, the M184V/I mutation, or both. This combination of drugs cannot therefore be recommended as alternative treatment in patients with HIV-1 who are fully virologically suppressed.

[Reducing the risk of blood-transmitted infections of HIV, hepatitis B or C virus in a teaching hospital in Amsterdam--evaluation of a protocol for needlestick accidents among hospital staff during the period 1997-2001]. / Risicoreductie van bloedoverdraagbare besmetting met HIV, hepatitis-B- of -C-virus in een opleidingsziekenhuis in Amsterdam--evaluatie van een protocol voor 'prikaccidenten' bij ziekenhuismedewerkers, 1997-2001.

OBJECTIVE: To evaluate a protocol for hospital staff aimed at reducing their risk of exposure to blood-transmitted infections. DESIGN: Prospective. METHOD: In August 1997 a protocol was introduced to the Onze Lieve Vrouwe Gasthuis Hospital in Amsterdam, with procedures to be followed after percutaneous or mucocutaneous blood contact in which there was a chance of transmission of hepatitis B (HBV) or C (HCV), as well as guidelines for the prescription of post-exposure prophylaxis (PEP) after accidents with an HIV risk. In the period 1 August 1997-30 June 2001 data were collected from registration forms that reported accidents and the ensuing events. RESULTS: A total of 403 accidents were reported by 138 (34.2%) physicians, 135 (33.5%) ward nurses, 46 (11.4%) operation assistants, 30 (7.4%) co-assistants, 21 (5.2%) analysts and 33 (8.2%) persons with another position. There was a constant increase in the number of reports over the period. The seroprevalence of the source patients was: 6.9% (25/360) HIV, 8.1% (6/74) HBV and 6.3% (23/363) HCV. PEP was prescribed on 46 occasions: 15 times for an HIV positive source and 31 times for what was initially an unknown HIV source. Following the introduction of a rapid HIV test in September 1999, there was a reduction in the number of unnecessary PEP prescriptions from 4 in 1997, 7 in 1998 and 16 in 1999 to 3 in 2000 and 1 in 2001. All 15 persons who were correctly started on a PEP treatment took the medication for a period of 28 days despite many side effects. No seroconversions were established during the follow-up period of 6 months.

Quantum energies of interfaces.

We present a method for computing the one-loop, renormalized quantum energies of symmetrical interfaces of arbitrary dimension and codimension using elementary scattering data. Internal consistency requires finite-energy sum rules relating phase shifts to bound state energies.

[Improved results in the treatment of acute myeloid leukemia - Results of study AML-BFM-93 in East Germany with comparisons to the preceding studies AML-I-82 and AML-II-87]. / Verbesserte Ergebnisse in der Therapie der akuten myeloischen Leukämie - Ergebnisse der Therapiestudie AML-BFM-93 in den neuen Bundesländern im Vergleich mit den Vorgängerstudien AML-I/82 und AML-II/87 der DDR.

BACKGROUND: Three multicenter studies were conducted in East Germany on the treatment of acute myeloid leukaemia in children. The latest of the three studies (AML-BFM-93-OST) was part of the common German study AML-BFM-93. PATIENTS AND METHODS: The total number of registered patients was 262. The number and dosage of administered chemotherapeutic agents was elevated with each new study. RESULTS: Both the remission rate (85 %) and the likelihood of an event free survival (52 % after 5 years) could be improved significantly in study AML-BFM-93-OST. The results of the common German study AML-BFM-93 were identical to those of the East German part AML-BFM-93-OST. Compared with international studies it was one of the most successful treatment strategies in children with AML. Patients who showed toxic side effects to heart, liver, kidneys, skin or nervous system during the chemotherapy had a significantly lower risk of relapse, once they overcame the intensive therapy. During the five years of study AML-BFM-93-OST, treatment results could be improved despite an unchanged therapy strategy. This may partly be due to the modernisations and restorations that were carried out in many East German hospitals in this time. CONCLUSIONS: The therapy regimen of study AML-BFM-93 allowed a substantial improvement in the treatment of children with AML. Further intensification of chemotherapy should only be undertaken in accordance to the individual sensitivity of each patient.

Trimethoprim-sulphamethoxazole as primary Pneumocystis carinii prophylaxis does not increase serum homocysteine levels in HIV-positive subjects.

Background: We recently observed that a short course of trimethoprim 300 mg b.i.d. in healthy volunteers can cause a substantial increase in fasting plasma homocysteine levels, up to concentrations reportedly associated with atherothrombotic complications. The purpose of this study was to determine whether primary Pneumocystis carinii prophylaxis (PCP) with trimethoprim-sulphamethoxazole (TMP-SMX) adversely affects serum homocysteine levels in HIV-positive patients. Methods: We studied 34 subjects [29 male, 5 female, mean age 36.8+/-7.9 (S.D.) years] with no prior AIDS-defining disease who required primary PCP prophylaxis (CD4+ T-cell count <200/mm(3)). The common dose of TMP-SMX was 80/400 mg (80 mg trimethoprim and 400 mg sulphamethoxazole) once daily. Serum total homocysteine levels were determined in four samples: two collected prior to the start of TMP-SMX and two collected on average 2.6+/-2.2 and 5.3+/-3.5 months into the first year of prophylactic therapy. Results: Mean serum homocysteine was 13.9+/-3.7 &mgr;mol/l pre-treatment and 14.4+/-5.0 &mgr;mol/l during treatment with TMP-SMX, a non-significant increase of 0.5 &mgr;mol/l (95% CI: -0.5 to +1.4, P=0.34). Folate levels were equally unaffected by TMP-SMX (13.1+/-6.5 nmol/l versus 13.3+/-5.3 nmol/l, before and during therapy, respectively). Baseline folate levels did not predict the response of homocysteine to TMP-SMX, and neither did age, gender, or serum creatinine. Conclusion: Long-term therapy with 80/400 mg TMP-SMX does not adversely affect homocysteine levels.

A new flux-orientated concept to derive critical levels for ozone to protect vegetation.

The current European critical levels for ozone (O3) to protect crops, natural and semi-natural vegetation and forest trees are based on a relative small number of open-top chamber experiments with a very limited number of plant species. Therefore, the working group "Effects of Ozone on Plants" of the Commission on Air Pollution Prevention of the Association of German Engineers and the German Institute of Standardization reanalysed the literature on O3 effects on European plant species published between 1989 and 1999. An exposure-response relationship for wild plant species and agricultural crops could be derived from 30 experiments with more than 30 species and 90 data points; the relationship for conifer and deciduous trees is based on 20 experiments with nine species and 50 data points. From these relationships maximum O3 concentrations for different risk stages are deduced, below which the vegetation type is protected on the basis of the respective criteria. Because it is assumed that the fumigation concentrations reflect the O3 concentrations at the top of the canopy, i.e. the upper surface boundary of the quasi-laminar layer if the micrometeorological big-leaf approach is applied, the application of these maximum O3 concentrations requires the transformation of O3 concentrations measured at a reference height above the canopy to the effective phytotoxic concentrations at the top of the canopy. Thus, the approach described in this paper is a synthesis of the classical concept of toxicology of air pollutants (critical concentrations) and the more toxicological relevant dose concept.

Toxicity and drug exposure in a quadruple drug regimen in HIV-1 infected patients participating in the ADAM study.

OBJECTIVE: To study the relationship between toxicity and the exposure to nelfinavir and saquinavir as part of a quadruple drug regimen. DESIGN: The ADAM study is a randomized study to investigate the feasibility of induction-maintenance therapy in HIV-1 infection. METHODS: HIV-1-infected patients with no prior use of antiretroviral treatment started induction therapy consisting of stavudine + lamivudine + nelfinavir + saquinavir for a period of 26 weeks. Data regarding toxicity of the quadruple regimen and exposure to the protease inhibitors were collected. RESULTS: Seven of the 65 patients enrolled had to switch therapy for reasons of toxicity within the first 26 weeks. Diarrhoea was frequently reported (49 of 65, one discontinuation), but could be relieved by using antidiarrhoeal agents. Laboratory monitoring revealed elevated liver enzymes (leading to four discontinuations) and mild to moderate elevations of triglycerides and cholesterol (nine and 23 of 65, respectively). The exposure to saquinavir and nelfinavir was lower than expected. Abdominal pain was associated with a higher exposure to nelfinavir or saquinavir. The association of nausea and abdominal distension with drug exposure appeared to vary over time. CONCLUSIONS: The quadruple drug regimen was quite well tolerated. Diarrhoea was frequently reported but could be relieved by the use of antidiarrhoeal agents. In comparison with other protease inhibitor combinations, lipid abnormalities in plasma were infrequent and mild. With the exception of diarrhoea, all gastrointestinal complaints observed were found to be associated with the level of exposure to nelfinavir or saquinavir. The exposure to the protease inhibitors was relatively low, although the virologic efficacy of the regimen used was satisfactory.

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. METHODS: Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). RESULTS: Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. CONCLUSIONS: Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.

Ozone threshold doses and exposure-response relationships for the development of ozone injury symptoms in wild plant species.

The relative ozone sensitivities of 25 German native herbaceous plant species, representative of arable field margins or disturbed habitats, were examined over three consecutive growing seasons. Plants were grown from seed, potted into natural soils and exposed in open-top chambers for the entire season to different ozone-exposure regimes covering a range of concentrations from <5 to 48 ppb (seasonal 8 h daily mean). The assessment of ozone effects was carried out by recording the first day of visible symptom appearance and the percentage of injured leaves at the end of vegetative growth. Species exhibited contrasting patterns of symptom expression under ozone stress, with either ozone-specific symptoms or ozone-enhanced foliar pigmentation and senescence. Classifications of species according to their ozone susceptibility varied depending on whether measurement was of the total extent of visible injury, ozone threshold doses for the incidence of symptoms, or modelled exposure-response relationships. The most sensitive species exhibiting ozone-specific symptoms were Cirsium arvense and Sonchus asper, which responded to accumulated ozone exposures <1500 ppb.h (AOT40). For these and three other species, an AOT40 peak of a single day was found to be responsible for the incidence of ozone-specific symptoms, i.e. injury occurred rapidly within a few days of the day with the highest AOT40, while other species responded only to longer-term ozone exposures. The relative ozone sensitivity of the species was calculated by combining the different sensitivity criteria, and possible systematic trends (taxonomic or evolutionary features) are pointed out. The results suggest it may be possible to use a particular group of native herbaceous plant species with contrasting patterns of ozone sensitivity as a biomonitoring system in the field. This allows plant responses to be related either to peak values or to prolonged ozone exposure, making it possible to distinguish between short- and long-term effects of ozone.

The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy.

OBJECTIVE: To investigate the relationship between exposure to antiretroviral drugs and the initial decline of plasma HIV-1 RNA. DESIGN: Open-label study in antiretroviral-naive HIV-1 infected patients using a quadruple drug regimen [nelfinavir (NFV), saquinavir (SQV), stavudine, and lamivudine]. METHODS: The elimination rate constant (k) for HIV-1 clearance was calculated during the first 2 weeks of treatment in 29 patients. Exposure to NFV and SQV was quantified on each study visit. Observed NFV and SQV concentrations were related to those expected in a reference population and a concentration ratio was calculated. The median concentration ratios for NFV and SQV, the baseline CD4+ lymphocyte count and baseline log10 HIV-1 RNA were correlated with k. RESULTS: A significant positive correlation was observed between k and the median NFV (P = 0.001) or SQV concentration ratio (P = 0.016) in univariate analysis. In multivariate analyses, the median NFV concentration ratio remained significantly correlated with k. CONCLUSIONS: The variation in the rate of decline of plasma HIV-1 RNA between patients after the initiation of a quadruple drug regimen could be explained by differences in exposure to NFV or SQV. Determination of k could be used to optimise further antiretroviral drug therapy and may be a first tool to assess antiretroviral activities of new or increasing doses of drugs administered in combination regimens. Furthermore, our data suggest that exposure to antiretroviral drugs should be incorporated in mathematical models to describe HIV-1 dynamics in more detail.

Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long-term use of multidrug regimens is difficult to sustain. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimise toxicity. We investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART in a randomised open-label study. METHODS: From March, 1997, we enrolled patients infected with HIV-1 with at least 200 CD4 cells/microL, at least 1000 HIV-1 RNA copies/mL in plasma, and no previous exposure to antiretroviral drugs. After 26 weeks of induction therapy (stavudine, lamivudine, saquinavir, and nelfinavir) patients were randomly allocated maintenance therapy (either stavudine and nelfinavir or saquinivir and nelfinavir) or prolonged induction therapy (if the plasma HIV-1 RNA concentration at weeks 24 and 25 was <50 copies/mL). FINDINGS: In February, 1998, we discontinued randomisation after an interim analysis. 62 patients had been enrolled. 39 (91%) of the 43 patients who were followed up for at least 26 weeks had an undetectable plasma HIV-1 RNA concentration at week 16. At week 26, 31 patients were randomly allocated treatment. Of these patients 25 had a total follow-up of at least 36 weeks. At week 36, a higher proportion of patients on maintenance therapy (nine [64%] of 14) had a detectable HIV-1 RNA than patients on prolonged induction therapy (one [9%] of 11, p=0.01). The initial virion-clearance rate during induction therapy was higher in five patients on maintenance therapy with a sustained undetectable plasma HIV-1 RNA concentration than in nine patients with recurrence of a detectable plasma HIV-1 RNA concentration at week 36 (0.35 vs 0.19 per day, respectively; p=0.0008). INTERPRETATION: The induction regimen provided a rapid suppression of viral replication to below 50 copies/mL. However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy. It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.