Deep Salvage Research Articles

Forest topsoil salvage and placement depth affects oil sands reclamation in the boreal forest.

Reclamation of disturbances from oil sands mining requires effective soil management to ensure successful plant establishment and to promote recovery of native plant communities. In this study we investigated the effects of salvage depths (shallow vs. deep) and placement depths (shallow vs. deep) of forest topsoil on plant establishment, species richness, and soil properties in two substrate types (sand and peat-mineral). Shallow salvage led to greater tree stem densities and higher canopy cover for most plant groups, although there was no significant difference in species richness between shallow and deep salvages. Deep placement generally resulted in greater canopy cover, while its effect on plant density was very small for most plant groups. On peat-mineral substrate, fewer differences were detected between shallow and deep salvage, and multiple treatments resulted in greater cover. Findings suggest that a balance between maximizing the area over which propagules are redistributed and providing sufficient resources for successful plant establishment is necessary. Forest topsoil from shallow salvages and deep placements is recommended when targeting increased site productivity and species diversity. In contrast, deep salvage should be used when the primary objective is to obtain maximum reclamation material volume. Salvage depth effects may be influenced by substrate type, with peat-mineral substrate providing more favourable conditions for plant establishment. Further research is needed to assess the long-term impacts of different salvage and placement depths on plant community development and the potential effects of substrate properties on soil and plant response.

PO 8411 MOLECULAR CHARACTERISATION OF GP41 AND GP120 V3 LOOP IN HIV-1C PATIENTS FAILING SALVAGE THERAPY IN BOTSWANA

BackgroundTriple class drug-resistant HIV-1 infection remains a global challenge in individuals with extensive antiretroviral treatment (ART) experience, in terms of high mortality and probability of onward transmission. New therapeutic options within old and new drug classes are therefore essential. We determined if patients failing salvage therapy in Botswana are eligible for maraviroc (MVC) and enfuvirtide (T20) viral entry inhibitors based on the coreceptor usage and drug-resistant mutations in envelope gp120 and gp41.MethodsA total of 38 deep salvage patients were included in the analysis. We amplified and sequenced gp41 and V3 regions of HIV-1 envelope. Drug resistance mutations were analysed according to the IAS-USA 2017 reference mutation lists. Coreceptor usage was determined using PSSM and Geno2Pheno using a false-positive rate (FPR) of 10%.ResultsAmong 38 participants, 34 (89%) were successfully sequenced and amplified gp41 and 26 (68%) gp120 V3 loop sequences were obtained. Major T20 mutation G36S was obtained in 1/34 samples (5.8%) within the study population. Polymorphisms I169V(97%), I135L(100%), E151A(70.6%) and N42S(70.6%) were detected in HR1 and HR2 of gp41. CXCR4 coreceptor associated use, mutation L34M in gp41 HR1 was detected in 2 samples (5%). Analysis of coreceptor usage showed (17/26) 65.4% use of CCR5, and a (9/26) 34.6% use of the CXCR4 coreceptor.ConclusionA moderately high proportion of treatment-experienced (deep salvage) participants had CXCR4 coreceptor using strains. The use of maraviroc in Botswana would require coreceptor tropism testing. Non-T20 treatment experience in Botswana reduces the prevalence of the major mutations that confer resistance to the drug. T20 is therefore a potential alternative drug for patients failing salvage therapy in Botswana.

P034: Darunavir-containing deep salvage regimens in routine clinical practice: a stewardship strategy

Antiretroviral therapies have proved life-saving in HIV infection, dramatically reducing morbidity and mortality. With longer survival, morbidities and mortalities in HIV infection are increasingly similar to the morbidities and mortalities associated with ageing. In treated HIV infection, the risk of these morbidities and mortalities is linked to immune activation, inflammation and coagulation indices. And in persons with treated HIV infection, failure to restore circulating CD4 T cell numbers is associated with a greater risk of morbidities and mortalities as well as to heightened levels of inflammation and coagulation. The drivers of immune activation, inflammation and coagulation in treated HIV infection are incompletely defined and could be related to sustained low levels of viral replication in tissues, to translocation of microbial products across a damaged gut mucosa, to replication of co-pathogens such as cytomegalovirus, to increased levels of inflammatory lipids, or to homeostatic responses to lymphocytopenia that may drive expansion of CD8 T cell numbers. We present here models that link inflammation and coagulation to morbid outcomes as well as to the pathogenesis of CD4 T cell restoration failure and CD8 T cell expansion.

Added Value of Deep Sequencing Relative to Population Sequencing in Heavily Pre-Treated HIV-1-Infected Subjects

ObjectiveTo explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects.MethodsIn a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological failure who also developed virologic failure to deep salvage therapy including, at least, darunavir, tipranavir, etravirine or raltegravir. Viral susceptibility was inferred before salvage therapy initiation and at virological failure using deep and population sequencing genotypes interpreted with the HIVdb, Rega and ANRS algorithms. The threshold level for mutant detection with deep sequencing was 1%.Results7 subjects with previous exposure to a median of 15 antiretrovirals during a median of 13 years were included. Deep salvage therapy included darunavir, tipranavir, etravirine or raltegravir in 4, 2, 2 and 5 subjects, respectively. Self-reported treatment adherence was adequate in 4 and partial in 2; one individual underwent treatment interruption during follow-up. Deep sequencing detected all mutations found by population sequencing and identified additional resistance mutations in all but one individual, predominantly after virological failure to deep salvage therapy. Additional genotypic information led to consistent decreases in predicted susceptibility to etravirine, efavirenz, nucleoside reverse transcriptase inhibitors and indinavir in 2, 1, 2 and 1 subject, respectively. Deep sequencing data did not consistently modify the susceptibility predictions achieved with population sequencing for darunavir, tipranavir or raltegravir.ConclusionsIn this subset of heavily pre-treated individuals, deep sequencing improved the assessment of genotypic resistance to etravirine, but did not consistently provide additional information on darunavir, tipranavir or raltegravir susceptibility. These data may inform the design of future studies addressing the clinical value of minority drug-resistant variants in treatment-experienced subjects.

The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

BackgroundAlthough being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations.ResultsBased on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options.Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks.ConclusionsIn this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002).In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.

Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure

Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. Double 148R + N155H mutants were also detected in 1.7% of viruses at virological failure in association with E138K and/or G163R. Our findings illustrate the ability of HIV-1 to escape from suboptimal antiretroviral drug pressure through selection of pre-existing drug-resistant mutants, underscoring the importance of using fully active antiretroviral regimens to treat all HIV-1-infected subjects.

Effective Treatment of Patients in a Deep Salvage Situation with "Non-Active HAART": Experiences with the Expert Advice System RADATA

Clinical studies suggest expert recommendations as a possibility to optimize highly active antiretroviral therapy (HAART) in patients with multi-drug resistant virus strains. An online system (RADATA) has been developed to provide expert advice for the drug therapy of HIV-infected patients. To evaluate the efficacy of expert-advice-guided HAART switches in patients with triple-class failure. Virological and immunological outcome of patients having undergone at least three prior ART regimens, including nucleoside inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) use, were analyzed. Changes in HIV-RNA and CD4-cell count were evaluated every 3 months. 183 patients with a median baseline viral load of 3.90 log copies/ml (1.88-6.54 log) and a CD4-cell count of 298 c/ll (5-910 c/ll) were eligible for analysis. The patients had a median of seven prior ART regimens and a treatment duration of 83 months. A median of three (range 0-8) NRTI-, two (0-7) thymidine-associated (TA), one (0-4) NNRTI-, and three (0-13) PI-associated resistance mutations were present at baseline. Despite available resistance analyses and expert recommendations, 66% (n = 119) of the patients started a new ART regimen without any active drugs according to the resistance analysis. The HIV-RNA declined by a median of 0.61 log and 0.92 log after 12 and 24 months, respectively, while the CD4-cell count rose by a median of +9 c/microl and +25 c/microl during this period. No significant differences related to number of prior regimens or number of active substances used could be found. Despite extensive pre-treatment and multiple resistances against prescribed HAART, our patients demonstrated a decline in viral load and a stable CD4-cell count over the observation period. We conclude that the activity of antiretroviral regimens is not exclusively explained by the current algorithms used for estimating antiretroviral drug activity.

Reversal of Major Genotypic Tipranavir Mutations Under Long-Term Treatment with Tipranavir/Ritonavir Itself with Very Limited Optimized Background, During Deep Salvage Antiretroviral Therapy

A reversal of key HIV protease mutations against tipranavir has been observed in a patient undergoing a late salvage antiretroviral therapy. Our patient initially introduced tipranavir/ritonavir in absence of an optimized background and novel drug classes, and nevertheless he experienced a virological-immunological benefit. Our report is a contribution to the present debate around the role of each single HIV protease mutation, and the validation of mutational "scores" (like the so-called tipranavir weighted score), to be applied to last-generation protease inhibitor compounds initially targeted on patients with limited, residual therapeutic options.

A new approach for ‘deep salvage’ trials in advanced HIV infection

One of the most difficult problems in HIV care today is the management of individuals infected with multidrug-resistant viruses. Well-controlled, carefully designed clinical trials have recently resulted in the approval of several new antiviral agents for the treatment of drug-resistant HIV. The design of these trials has come at the cost of the predictable emergence of drug-resistant viruses among individuals randomly assigned to receive a suboptimal revised treatment regimen. We propose here a different approach to the evaluation of drug efficacy in individuals harbouring multidrug-resistant HIV.

Promising New Options for Treatment-Experienced Patients

In October 2005, the U.S. Department of Health and Human Services updated its guidelines to state that even in deep salvage therapy, the goal of

A High Accuracy Hybrid Navigation System for Unmanned Underwater Vehicle

The development of small, light weight, low power navigation system for guidance of both tethered and autonomous Unmanned Underwater Vehicle (UUV) is required in applications such as deep salvage, oil and gas well head and pipe line laying and maintenance, etc. All have stringent position requirements in order to define target locations followings the initial find, minimize search time for return missions, as well as support of autopilot functions. In these applications mainly an accurate Sonar Doppler Velocity Log (DVL) was used for Inertial Navigation System (INS) error corrections. But the settlement of DVL is not affordable to various UUV so that not convenient to low cost and small UUV. In this paper we propose a new algorithm for combining the low cost but highly accurate INS with Water Screw Speed (WSS) of the UUV efficiently. In order to evaluate our algorithm we produced the data acquisition system and after several experimental run, we simulated this algorithm searching the error correlation time and noise variance of these estimations.

Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease

The virological and immunological response to an efavirenz-containing rescue regimen was compared with that of a nevirapine-containing one in a prospective, open-label 12-month study performed in patients previously treated with ≥12 months of nucleoside analogue monotherapy, and ≥15 months of indinavir- or ritonavir-containing HAART. Pooled laboratory data were assessed according to change or continuation of nucleoside analogues, at the time of start of salvage treatment. An improvement of markers of HIV disease progression occurred in all 59 evaluable patients (with a higher viral load decrease in the efavirenz over the nevirapine group at the third month), but the virological response was neither complete nor sustained at the end of study, irrespective of efavirenz or nevirapine adjunct, and complete viral suppression was attained in only 16.9% of subjects. A progressively increasing mean CD4+ lymphocyte count characterized the immunological response of all patients. The 35 patients who changed at least one nucleoside analogue when introducing salvage therapy had a better outcome, irrespective of the non-nucleoside reverse transcriptase inhibitor chosen. Rescue strategies are increasingly needed in HIV-infected patients treated for a long time with HAART. The association of nelfinavir, a non-nucleoside reverse transcriptase inhibitor, and dual nucleoside analogues, is popular among patients who fail first-line HAART. When prolonged prior treatment with nucleoside analogue monotherapy and HAART are of concern, and a quite elevated viral load is present, this salvage regimen may not allow a complete and sustained virological response in a 1-year period, while a more favourable immunological recovery can be expected. However, the concurrent change of nucleoside analogues significantly improves treatment outcome.

Deep sea salvage of flight recorders

Un submersible telecommande, fonctionnant aux limites de sa conception, a montre que le sauvetage a 2000 m est a la fois faisable et economique, lorsqu'il retrouve les enregistreurs des voix du cokpit d'un Boeing 747 situe a 2040 m de profondeur dans l'ocean Atlantique

Two-Ton Diving Ball for Use in Deep Sea Salvage Tested

Two-Ton Diving Ball for Use in Deep Sea Salvage Tested

IN RE DEEP SEA DIVING AND SALVAGE LTD.

IN RE DEEP SEA DIVING AND SALVAGE LTD.