902 resultados para post vaccinal response
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The objective of this study was to evaluate the effect of one or two doses of the anti-rabies vaccination on the serum concentration of cortisol and the humoral immune response in cattle as well as the correlation between serum cortisol concentrations and the titers of rabies-neutralizing antibodies. Nelore cattle were randomly assigned to one of three groups, which were vaccinated with one dose of rabies vaccine (group GVSR, N = 15), two doses of rabies vaccine (group GVR, N = 15) or were not vaccinated (group Gc, N = 15). A commercial liquid inactivated rabies vaccine was used. The stressors imposed on the cattle were vaccination, corral handling and the presence of people. Blood samples were collected on days 0, 30 and 60 post-vaccination. Serum cortisol concentrations were determined using a solid-phase radioimmunoassay, and rabies antibody titers were determined using a serum neutralization test with BHK21 cells (RFFIT). Both serum cortisol concentrations and antibody titers increased after the second (booster) vaccination (P < 0.05). In all the groups, the serum cortisol concentrations increased after the cattle were handled in the corral (P < 0.05). No correlation was observed between the serum cortisol concentrations and the antibody titers with any treatment or on any observation day. In conclusion, booster vaccination is indispensable for primovaccinated cattle in achieving high and protective levels of rabies antibodies. Although booster vaccination and frequent cattle handling in corrals are stressors, the response is not strong enough to cause immunosuppression in cattle.
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Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.
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Low-level laser therapy is a tool employed in the management of post-operative inflammation process and in the enhancement of reparative process. The aim of the study was to perform histological evaluation of dental and periodontal ligament of rats central upper-left incisor teeth re-implanted and irradiated with low-level laser (InGaAl, 685 nm, 50 J/cm(2)) 15, 30, and 60 days after re-implantation. Seventy-two male rats had the central upper left incisor removed and kept for 15 min on dry gauze before replantation. Laser was irradiated over the root surface and empty alveolus prior replantation and over surrounding mucosa after the re-implantation. After histological procedures, all slices were analyzed regarding external resorption area and histological aspects. We observed an increase of root resorption (p < 0.05) in the control group compared to the laser group at 15, 30, and 60 days. These results showed that the laser groups developed less root resorption areas than the control group in all experimental periods. Additionally, histological analysis revealed less inflammatory cells and necrotic areas in laser groups.
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The expression of Langerhans cell (LC) and dermal dendritic cell (dDC) as well as T CD4+ and CD8+ immune responses was evaluated in the skin of BALB/c mice experimentally infected by L. (L.) amazonensis (La) and L. (V.) braziliensis (Lb). At 4th and 8th weeks post infection (PI), skin biopsies were collected to determine the parasite load and CD207+, CD11c+, CD4+, CD8+, iNOS+ cellular densities. Cytokine (IFN-?, IL-4 and IL-10) profiles were also analysed in draining lymph node. At 4th week, the densities of CD207+ and CD11c+ were higher in the La infection, while in the Lb infection, these markers revealed a significant increase at 8th week. At 4th week, CD4+ and CD8+ were higher in the La infection, but at 8th week, there was a substantial increase in both markers in the Lb infection. iNOS+ was higher in the Lb infection at 4th and 8th weeks. In contrast, the parasite load was higher in the La infection at 4th and 8th weeks. The concentration of IFN-? was higher in the Lb infection, but IL-4 and IL-10 were higher in the La infection at 4th and 8th weeks. These results confirm the role of the Leishmania species in the BALB/c mice disease characterized by differences in the expression of dendritic cells and cellular immune response.
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PURPOSE: To assess comparatively the inflammatory response that follows CO2 or Ringer's lactate joint capsular distension of horses submitted to experimental arthroscopy METHODS: Each animal was submitted to a bilateral tarsocrural arthroscopy employing gas distention in one joint and fluid distention in the contralateral joint. Synovial fluid was evaluated at 0, six, 12, 24 and 48 hours post-operative. RESULTS: The use of CO2 for arthroscopy causes an acute and mild synovitis alike to the liquid capsular distension, showing similar synovial fluid increase of leukocytes, TP, and TNF-alpha. Although synovial fluid PGE(2) content was higher in joints submitted to CO2 distension, lower levels of hemoglobin and leukocytes oxidative burst after surgery indicates that CO2 arthroscopy decreased intra-articular bleeding and activation of infiltrating leukocytes. CONCLUSIONS: The use of CO2 for arthroscopic examination causes acute and mild synovitis that is similar to the effects caused by the liquid capsular distension. CO2 also seems to decrease intra-articular bleeding and activation of leukocytes.
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Nebulized l-epinephrine has been recommended for the treatment of viral croup. However, the few studies assessing its effect on post-extubation stridor (PES) have shown conflicting results. We compared the efficacy and safety of nebulized l-epinephrine at three different doses for the treatment of PES. We conducted a prospective, randomized, double-blind trial including all consecutive children with a PES score of a parts per thousand yen4 (Westley score). The primary efficacy outcome was change in PES score at 40 min. A reduction of a parts per thousand yen2 points in stridor score was defined as clinically significant. A total of 96 patients were randomly assigned to receive one of three doses of nebulized l-epinephrine upon achieving a PES score of 4 or more following extubation. Stridor score and vital signs were recorded before treatment, and at 20, 40, 60 and 180 min after nebulization. Baseline characteristics were similar among all study groups. No significant difference was detected among the treatments based on change in Westley score by intent-to-treat analysis. In addition, the difference in the number of patients who clinically improved among the treatment groups was not significant (p = 0.54). Patients receiving 5 ml nebulized epinephrine had a significant increase of systolic and diastolic blood pressure at 40 and 180 min. Nebulized l-epinephrine at doses of 0.5, 2.5 and 5 ml demonstrated a lack of dose response in effect on PES and a modestly clinically significant increase in undesired side effects (heart rate and blood pressure) at higher doses.
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Objectives To analyse the perspective of clinical research stakeholders concerning post-trial access to study medication. Methods Questionnaires and informed consents were sent through e-mail to 599 ethics committee (EC) members, 290 clinical investigators (HIV/AIDS and Diabetes) and 53 sponsors in Brazil. Investigators were also asked to submit the questionnaire to their research patients. Two reminders were sent to participants. Results The response rate was 21%, 20% and 45% in EC, investigators and sponsors' groups, respectively. 54 patients answered the questionnaire through their doctors. The least informative item in the consent form was how to obtain the study medication after trial. If a benefit were demonstrated in the study, 60% of research participants and 35% of EC answered that all patients should continue receiving study medication after trial; 43% of investigators believed the medication should be given to participants, and 40% to subjects who participated and benefited from treatment. For 50% of the sponsors, study medication should be assured to participants who had benefited from treatment. The majority of responders answered that medication should be provided free by sponsors; investigators and sponsors believed the medication should be kept until available in the public health sector; EC members said that the patient should keep the benefit; patients answered that benefits should be assured for life. Conclusions Due to the study limitations, the results cannot be generalised; however, the data can contribute to discussion of this complex topic through analysing the views of stakeholders in clinical research in Brazil.
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Background: Reactive oxygen species (ROS) are formed under natural physiological conditions and are thought to play an important role in many human diseases. A wide range of antioxidants are involved in cellular defense mechanisms against ROS, which can be generated in excess during stressful conditions, these include enzymes and non-enzymatic antioxidants. The aim of this study was to evaluate the antioxidant responses of mice to two diets control, commercial and the purified AIN 93 diet, commonly used in experiments with rodents. Results: Malondialdehyde (MDA) and hydrogen peroxide (H2O2) concentrations and superoxide dismutase (SOD) and glutathione reductase (GR) activities determined in the liver were lower in the group of mice fed with the AIN 93 diet, while catalase (CAT) activity was higher in the same group, when compared to the group fed on the commercial diet. Liver glutathione peroxidase (GSH-Px) activity was similar in the groups fed on either AIN 93 or the commercial diets. Two SOD isoforms, Mn-SODII and a Cu/Zn-SODV, were specifically reduced in the liver of the AIN 93 diet fed animals. Conclusions: The clear differences in antioxidant responses observed in the livers of mice fed on the two diets suggest that the macro- and micro-nutrient components with antioxidant properties, including vitamin E, can promote changes in the activity of enzymes involved in the removal of the ROS generated by cell metabolism.
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BACKGROUND: Scleroderma is a chronic autoimmune disease characterized by progressive connective tissue sclerosis and microcirculatory changes. Localized scleroderma is considered a limited disease. However, in some cases atrophic and deforming lesions may be observed that hinder the normal development. Literature reports indicate phototherapy as a therapeutic modality with favorable response in cutaneous forms of scleroderma. OBJECTIVES: This study had the purpose of assessing the phototherapy treatment for localized scleroderma. METHODS: Patients with localized scleroderma were selected for phototherapy treatment. They were classified according to the type of localized scleroderma and evolutive stage of the lesions. Clinical examination and skin ultrasound were used to demonstrate the results thus obtained. RESULTS: Some clinical improvement was observed after an average of 10 phototherapeutic sessions. All skin lesions were softer at clinical palpation with scores reduction upon pre and post treatment comparison. The ultrasound showed that most of the assessed lesions presented a decrease in dermal thickness, and only five maintained their previous measure. Treatment response was similar regardless of the type of phototherapeutic treatment employed. CONCLUSIONS: The proposed treatment was effective for all lesions, regardless of the phototherapeutic modality employed. The improvement was observed in all treated skin lesions and confirmed by clinical evaluation and skin ultrasound.
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The aim of the present study was to evaluate the LH surge after EB (estradiol benzoate) or GnRH administration with or without P4 (progesterone) pre-exposure in ovariectomized (OVX) buffalo cows. Females were randomly assigned to receive an intravaginal P4 device (D0–D9). They were then given EB 24 h or GnRH 36 h post-P4 device removal (factorial 2×2, n=6 per group). Blood collection for LH measurement began 36 h after the P4 device removal and continued at 3 h intervals. The area under the LH curve (AUC; 30.2 ng2 and 13.41 ng2; P=0.007) and the area of the LH peak (AP; 19.0 ng2 and 8.9 ng2; P=0.009) were greater for EB than GnRH. We did not observe an effect of P4 pre-exposure on the AUC and AP. Furthermore, there was no interaction between P4 pre-exposure and EB or GnRH treatment on the AUC and AP. However, there was an interaction (P<0.01) between P4 pre-exposure and the type of inducer (EB or GnRH) to release a preovulatory-like LH surge at the beginning (BP), final (FP) and time (TP) of the LH peak. The P4 pre-exposure anticipated the BP (2.5 and 7.4 h), TP (6.0 and 12.0 h) and FP (11.5 and 17.1 h) when EB was used to induce a preovulatory-like LH surge (P<0.01). However, there was no effect of P4 pre-exposure on BP (0.4 and 0.4 h), TP (3.0 and 3.0 h) and FP (5.9 and 6.1 h) with GnRH treatment. There was also no effect of the pre-exposure to P4, type of inducer or interaction on the amplitude of the LH peak. We concluded that EB therefore led to greater LH release than GnRH, and pre-exposure to P4 before EB administration anticipated the preovulatory-like LH surge in buffalo cows.
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INTRODUCTION: With the aim of searching genetic factors associated with the response to an immune treatment based on autologous monocyte-derived dendritic cells pulsed with autologous inactivated HIV, we performed exome analysis by screening more than 240,000 putative functional exonic variants in 18 HIV-positive Brazilian patients that underwent the immune treatment. METHODS: Exome analysis has been performed using the ILLUMINA Infinium HumanExome BeadChip. zCall algorithm allowed us to recall rare variants. Quality control and SNP-centred analysis were done with GenABEL R package. An in-house implementation of the Wang method permitted gene-centred analysis. RESULTS: CCR4-NOT transcription complex, subunit 1 (CNOT1) gene (16q21), showed the strongest association with the modification of the response to the therapeutic vaccine (p=0.00075). CNOT1 SNP rs7188697 A/G was significantly associated with DC treatment response. The presence of a G allele indicated poor response to the therapeutic vaccine (p=0.0031; OR=33.00; CI=1.74-624.66), and the SNP behaved in a dominant model (A/A vs. A/G+G/G p=0.0009; OR=107.66; 95% CI=3.85-3013.31), being the A/G genotype present only in weak/transient responders, conferring susceptibility to poor response to the immune treatment. DISCUSSION: CNOT1 is known to be involved in the control of mRNA deadenylation and mRNA decay. Moreover, CNOT1 has been recently described as being involved in the regulation of inflammatory processes mediated by tristetraprolin (TTP). The TTP-CCR4-NOT complex (CNOT1 in the CCR4-NOT complex is the binding site for TTP) has been reported as interfering with HIV replication, through post-transcriptional control. Therefore, we can hypothesize that genetic variation occurring in the CNOT1 gene could impair the TTP-CCR4-NOT complex, thus interfering with HIV replication and/or host immune response. CONCLUSIONS: Being aware that our findings are exclusive to the 18 patients studied with a need for replication, and that the genetic variant of CNOT1 gene, localized at intron 3, has no known functional effect, we propose a novel potential candidate locus for the modulation of the response to the immune treatment, and open a discussion on the necessity to consider the host genome as another potential variant to be evaluated when designing an immune therapy study
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Adipose tissue-derived mesenchymal stem cells (ADSC) exhibit immunosuppressive capabilities both in vitro and in vivo. Their use for therapy in the transplant field is attractive as they could render the use of immunosuppressive drugs unnecessary. The aim of this study was to investigate the effect of ADSC therapy on prolonging skin allograft survival. Animals that were treated with a single injection of donor allogeneic ADSC one day after transplantation showed an increase in donor skin graft survival by approximately one week. This improvement was associated with preserved histological morphology, an expansion of CD4(+) regulatory T cells (Treg) in draining lymph nodes, as well as heightened IL-10 expression and down-regulated IL-17 expression. In vitro, ADSC inhibit naïve CD4(+) T cell proliferation and constrain Th-1 and Th-17 polarization. In summary, infusion of ADSC one day post-transplantation dramatically increases skin allograft survival by inhibiting the Th-17 pathogenic immune response and enhancing the protective Treg immune response. Finally, these data suggest that ADSC therapy will open new opportunities for promoting drug-free allograft survival in clinical transplantation.
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Negli ultimi decenni la Politica Agricola Comune (PAC) è stata sottoposta a diverse revisioni, più o meno programmate, che ne hanno modificato gli obiettivi operativi e gli strumenti per perseguirli. In letteratura economica agraria sono state eseguite diverse ricerche che affrontano analisi ex-ante sui possibili impatti delle riforme politiche, in particolare al disaccoppiamento, riguardo all’allocazione dei terreni alle diverse colture e all’adozione di tecniche di coltivazione più efficienti. Ma tale argomento, nonostante sia di grande importanza, non è stato finora affrontato come altri temi del mondo agricolo. Le principali lacune si riscontrano infatti nella carenza di analisi ex-ante, di modelli che includano le preferenze e le aspettative degli agricoltori. Questo studio valuta le scelte di investimento in terreno di un’azienda agricola di fronte a possibili scenari PAC post-2013, in condizioni di incertezza circa le specifiche condizioni in cui ciascuno scenario verrebbe a verificarsi. L’obiettivo è di ottenere indicazioni utili in termini di comprensione delle scelte di investimento dell’agricoltore in presenza di incertezza sul futuro. L’elemento maggiormente innovativo della ricerca consiste nell’applicazione di un approccio real options e nell’interazione tra la presenza di diversi scenari sul futuro del settore agricolo post-2013, e la componente di incertezza che incide e gravita su di essi. La metodologia adottata nel seguente lavoro si basa sulla modellizzazione di un’azienda agricola, in cui viene simulato il comportamento dell’azienda agricola in reazione alle riforme della PAC e alla variazione dei prezzi dei prodotti in presenza di incertezza. Mediante un modello di Real Option viene valutata la scelta della tempistica ottimale per investire nell’acquisto di terreno (caratterizzato da incertezza e irreversibilità). Dai risultati emerge come in presenza di incertezza all’agricoltore convenga rimandare la decisione a dopo il 2013 e in base alle maggiori informazioni disponibili eseguire l’investimento solo in presenza di condizioni favorevoli. La variazione dei prezzi dei prodotti influenza le scelte più dell’incertezza dei contributi PAC. Il Real Option sembra interpretare meglio il comportamento dell’agricoltore rispetto all’approccio classico del Net Present Value.
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In allogeneic hematopoietic stem cell transplantation (allo-HSCT), alloreactive T lymphocytes of donor origin mediate the beneficial graft-versus-leukemia effect but also induce graft-versus-host disease (GvHD). Since human leukocyte antigens (HLA) mismatch alleles represent major targets of alloreactive T lymphocytes, patient and donor are usually matched for the class I molecules A, B, C, and for the class II molecules DRB1 and DQB1, in order do reduce the risk of GvHD. The HLA-DPB1 locus, however, is still ignored in donor selection. Interestingly, clinical studies have demonstrated that disparities at HLA-DQB1 alleles as well as distinct HLA DPB1 mismatch constellations do not adversely affect the outcome of allo-HSCT. It has also been shown that HLA class II is predominantly expressed on hematopoietic cells under non-inflammatory conditions. Therefore, this PhD thesis focused on the application of CD4 T cells in adoptive immunotherapy of leukemias.rnIn the first part of this thesis we developed a rapid screening approach to detect T-cell reactivity of donors to single HLA class II mismatch alleles. Allo-HLA reactivity was measured in naive, memory, and entire CD4 T cells isolated from PBMC of healthy donors by flow cytometric cell sorting according to expression of the differentiation markers CD45RA, CD45RO, CD62L, and CCR7. T-cell populations were defined by a single marker to facilitate translation into a clinical-grade allo-depletion procedure. Alloreactivity to single HLA-DR/-DQ mismatch alleles was analyzed in short-term mixed lymphocyte reactions (MLR) in vitro. As standard antigen-presenting cells, we used the HLA-deficient cell line K562 upon electroporation with single HLA-DR/-DQ allele mRNA. We observed in IFN-γ ELISpot assays that allo-HLA-reactivity preferentially derived from subsets enriched for naive compared to memory T cells in healthy donors, irrespective of the HLA mismatch allele. This separation was most efficient if CD62L (P=0.008) or CD45RA (P=0.011) were used as marker. Median numbers of allo-HLA-reactive effector cells were 3.5-fold and 16.6-fold lower in CD62Lneg and CD45RAneg memory CD4 T cells than in entire CD4 T cells, respectively. In allele-specific analysis, alloreactivity to single HLA-DR alleles clearly exceeded that to HLA-DQ alleles. In terms of alloproliferation no significant difference could be observed between individual CD4 T-cell subsets. rnThe second part of this thesis dealed with the generation of allo-HLA-DQ/-DP specific CD4 T cells. Naive CD45RApos CD4 T cells isolated from healthy donor PBMC by flow cytometric cell sorting were stimulated in MLR against single allo-HLA-DQ/-DP alleles transfected into autologous mature monocyte-derived dendritic cells by mRNA electroporation. Rapidly expanding HLA-DQ/-DP mismatch reactive T cells significantly recognized and cytolysed primary acute myeloid leukemia (AML) blasts, fibroblasts (FB) and keratinocytes (KC) in IFN-γ ELISpot and 51chromium release assays if the targets carried the HLA DQ/ DP allele used for T cell priming. While AML blasts were recognized independent of pre-incubating them with IFN-γ, recognition of FB and KC required IFN-γ pre treatment. We further investigated HLA class II expression on hematopoietic and non-hematopoietic cells by flow cytometry. HLA class II was not detected on primary FB, KC, and non-malignant kidney cells, but was expressed at significant levels on primary AML blasts and B-LCL. Up-regulation of HLA class II expression was observed on all cell types after pre-incubation with IFN-γ.rnIn summary, the novel K562-HLA based MLR approach revealed that naive-depleted CD4 T-cell subsets of healthy individuals contain decreased allo-HLA reactivity in vitro. We propose the application of CD45RAneg naive-depleted CD4 T cells as memory T cell therapy, which might be beneficial for HLA-mismatched patients at high-risk of GvHD and low-risk of leukemia relapse. Memory T cells might also provide important post-transplant immune functions against infectious agents. Additionally, the screening approach could be employed as test system to detect donors which have low risks for the emergence of GvHD after allo-HSCT. In the second part of this thesis we developed a protocol for the generation of allo-HLA-DQ/-DP specific CD4 T cell lines, which could be applied in situations in which patient and donor are matched in all HLA alleles but one HLA-DQ/-DP allele with low GvHD potential. These T cells showed lytic activity to leukemia cells while presumably sparing non-hematopoietic tissues under non-inflammatory conditions. Therefore, they might be advantageous for allo-HSCT patients with advanced stage AML after reduced-intensity conditioning and T-cell depletion for the replenishment of anti-leukemic reactivity if the risk for disease relapse is high. rn
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Die oberflächennahe Geothermie leistet im Bereich der Nutzung regenerativer Wärme einen wichtigen Beitrag zum Klima- und Umweltschutz. Um die technische Nutzung oberflächennaher Geothermie zu optimieren, ist die Kenntnis der Beschaffenheit des geologischen Untergrundes ausschlaggebend. Die vorliegende Dissertation befasst sich mit der Bestimmung verschiedener Untergrundparameter an einem Erdwärmesondenfeld. Es wurden Untersuchungen zur Bestimmung der Wärmeleitfähigkeit wie der enhanced Thermal Response Test (eTRT), sowie eine Untergrund-Temperaturüberwachung im ersten Betriebsjahr durchgeführt. Die Überwachung zeigte keine gegenseitige Beeinflussung einzelner Sonden. Ein Vergleich zwischen dem geplanten und dem tatsächlichem Wärmebedarf des ersten Betriebsjahres ergab eine Abweichung von ca. 35%. Dies zeigt, dass die Nutzungsparameter der Anlage deren Effizienz maßgeblich beeinflussen können. Der am Beispielobjekt praktisch durchgeführte eTRT wurde mittels numerischer Modellierung auf seine Reproduzierbarkeit hin überprüft. Bei einem rein konduktiven Wärmetransport im Untergrund betrug die maximale Abweichung der Messung selbst unter ungünstigen Bedingungen lediglich ca. 6% vom zu erwartenden Wert. Die Detektion von grundwasserdurchflossenen Schichten ist in den Modellen ebenfalls gut abbildbar. Problematisch bleibt die hohe Abhängigkeit des Tests von einer konstanten Wärmezufuhr. Lediglich die Bestimmung der Wärmeleitfähigkeit über das Relaxationsverhalten des Untergrundes liefert bei Wärmeeintragsschwankungen hinreichend genaue Ergebnisse. Die mathematische Nachbearbeitung von fehlerhaften Temperaturkurven bietet einen Einstiegspunkt für weiterführende Forschung.