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• Bayesian inference based state estimation of voltage dips in power system. • Network uncertainties have been incorporated. • A iterative sampling process is used to accelerate the Monte Carlo integration. • The required measurement set-up is quantified. The magnitudes of voltage dips on non-monitored buses can be estimated by applying Bayes's theorem with measured voltage dips on a limited number of monitored buses. Bayes's theorem is used to obtain the grid conditions, including the network impedance, load, distributed generation vector, and short-circuit location, from which the voltage magnitudes along the feeder can be calculated. In order to implement this approach effectively, it is necessary to understand which parameters among the grid conditions are more significant for the estimation performance and how the uncertainties associated with these parameters affect the estimation results. Moreover, since the measurement structure provides observations to calculate the posterior distribution from the prior distribution of the grid conditions. The measurement parameters, quantities, and accuracy levels are varied in simulations to obtain an optimum measurement structure balancing between the cost and the measurement performance. This paper presented the results of the sensitivity studies which have been done on the IEEE 13-Bus and 123-Bus test systems. The results shows the performance of the voltage dip state estimation approach is less sensitive to the uncertainty level of the load while more sensitive to those of the DG, the short-circuit power, the zero sequence impedance of the cable and the short-circuit resistance. The voltage measurement accuracy is more important than that of current and phase angles. The proposed method shows much stronger robustness compared to the conventional one and the estimation performance can be improved through several measures, e.g. adding more measurement points. [ABSTRACT FROM AUTHOR]

The introduction of electric vehicles and photovoltaics is changing the residential electricity consumption. Distribution network operators (DNO) are investing in an advanced metering infrastructure (AMI) to enable cost reduction through smart grid applications. The DNO also benefits from the additional measurement data the AMI gives for the network planning process. The availability of AMI data can be limited by the cost of communication and by privacy concerns. To determine the social welfare of an AMI, the economic gains should be estimated. For the planning of the low voltage (LV) network, a method for determining the value of an AMI still needs to be developed. Therefore, a planning methodology which allows various levels of measurement data availability has been developed. By applying this approach the value of different levels of AMI from an LV-network planning perspective can be determined. To illustrated the application of this approach a case study for the LV-network of a Dutch DNO is performed. The results show that an increase in measurement data can lead to €49-254 lower LV-network reinforcement costs. A detailed analysis of the results shows that already 50% of the possible cost reduction can be achieved if only 65% of the households have AMI data available. [ABSTRACT FROM AUTHOR]

In the residential sector, with the introduction of electric vehicles and photovoltaics, developments are taking place which have an impact on residential load curves. In order to assess the integration of these new types of technologies on both the generation and load side, as well as to develop mitigation strategies like demand side management, detailed information is required about the load curve of a household. To gain knowledge about this load curve a residential load model is developed based on publicly available data. The model utilises a Markov Chain Monte Carlo method to model the occupancy in a household based on time use surveys, which together with weather variables, neighbourhood characteristics and behavioural data are used to model the switching pattern of appliances. The modelling approach described in this paper is applied for the situation in the Netherlands. The resulting load curve probability distributions are validated with smart meter measurements for 100 Dutch households for a week. The validation shows that the model presented in this paper can be employed for further studies on demand side management approaches and integration issues of new appliances in distribution grids. [ABSTRACT FROM AUTHOR]

The shift to more renewable electricity generation, electrification of heating and transportation and the rise of ICT and energy storage lead to changes in the distribution of electricity. To facilitate the transition towards a clean sustainable power system distribution network operators are required to act proactively to these changes. To optimally capitalise on these changes it is imperative to have a clear and complete overview of the main developments and their effects on the distribution network. The technical, social, regulatory and economical effects of the renewable energy and ICT driven energy transition are discussed based on requirements which the distribution network should comply with. The discussed technologies all have effects on multiple requirements for the distribution network and the mitigation of unwanted effects should be assessed on these areas simultaneously. This can ensure that the future distribution network is best equipped to deal with the renewable energy and ICT driven energy transition. The overview of the requirements shows that the capacity, regulation and power quality are the main requirements which are affected by the renewable energy and ICT driven energy transition. [ABSTRACT FROM AUTHOR]

We report the selection of enfuvirtide-resistant human immunodeficiency virus type 1 in cerebrospinal fluid, resulting in subsequent loss of viral suppression in the plasma. This case report emphasizes the potential danger of low-level penetration of entry inhibitors into the central nervous system. [ABSTRACT FROM AUTHOR]

BACKGROUND: Airway infection with influenza virus induces local expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which has been shown to enhance inflammatory mediator responses in vitro. Because secondary pneumococcal infections occurring shortly after recovery from influenza are associated with enhanced inflammatory responses, we hypothesized that IDO activity contributes to the enhanced response to bacterial challenges in mice previously infected with influenza virus. METHODS: On day 14 after influenza virus infection (with strain A/PR/8/34), C57Bl/6 mice were intranasally inoculated with 1 x 10(4) colony-forming units of S. pneumoniae (serotype 3). Matrix-driven delivery pellets that contained 70 mg of the IDO inhibitor 1-methyl-DL-tryptophan (MeTrp) released over a period of 7 days were subcutaneously implanted 48 h before pneumococcal infection. RESULTS: MeTrp treatment resulted in a 20-fold reduction in pneumococcal outgrowth 48 h after bacterial inoculation. Remarkably, pulmonary levels of interleukin-10 and tumor necrosis factor-alpha were significantly reduced in mice treated with MeTrp. CONCLUSIONS: Our data suggest that IDO expression during influenza virus infection alters the inflammatory response and facilitates the outgrowth of pneumococci during secondary bacterial pneumonia. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

During summer and fall, enterovirus infections are responsible for a considerable proportion of hospitalizations of young infants. We prospectively studied the incidence of enterovirus infections via real-time polymerase chain reaction (PCR) in blood, feces, and cerebrospinal fluid samples from infants ⩽ 60 days old who had received a clinical diagnosis of sepsis. Forty-five patients were included: 19 were admitted to the pediatric wards of 2 general hospitals, and 26 had been hospitalized since birth in the neonatal intensive care unit (NICU) of a tertiary care hospital. None of the NICU patients developed enteroviral disease. In contrast, an enterovirus was detected in 11 (58%) of the patients admitted to the 2 general hospitals, 10 of whom (53%) showed evidence of systemic infection. Enterovirus infections are an important cause of sepsis in infants admitted to the hospital. Real-time PCR in serum was a rapid and sensitive method for diagnosis of enterovirus infection. [ABSTRACT FROM AUTHOR]

Introduction: HIV reservoir quantification is essential for evaluation of HIV curative strategies and may provide valuable insights about reservoir dynamics during antiretroviral therapy. The Intact Proviral DNA Assay (IPDA) provides the unique opportunity to quantify the intact and defective reservoir. The current IPDA is optimized for HIV-1 subtype B, the dominant subtype in resource-rich settings. However, subtype C is dominant in Sub-Saharan Africa, jointly accounting for around 60% of the pandemic. We developed an assay capable of quantifying intact and defective proviral HIV-1 DNA of subtype B and C. Methods: Primer and probe sequences were strategically positioned at conserved regions in psi and env and adapted to subtype B&C. In silico analysis of 752 subtype B and 697 subtype C near-full length genome sequences (nFGS) was performed to predict the specificity and sensitivity. Gblocks were used to determine the limit of blank (LoB), limit of detection (LoD), and different annealing temperatures were tested to address impact of sequence variability. Results: The in silico analysis showed that the HIV-1 B&C IPDA correctly identified 100% of the intact subtype B, and 86% of the subtype C sequences. In contrast, the original IPDA identified 86% and 12% of these subtype B and C sequences as intact. Furthermore, the HIV-1 B&C IPDA correctly identified hypermutated (87% and 88%) and other defective sequences (73% and 66%) for subtype B and C with comparable specificity as the original IPDA for subtype B (59% and 63%). Subtype B cis-acting sequences were more frequently identified as intact by the HIV-1 B&C IPDA compared to the original IPDA (39% and 2%). The LoB for intact proviral DNA copies was 0, and the LoD for intact proviral DNA copies was 6 (> 95% certainty) at 60 °C. Quantification of 2–6 copies can be performed with > 80% certainty. Lowering the annealing temperature to 55 °C slightly lowered the specificity but prevented exclusion of samples with single mutations in the primer/probe region. Conclusions: We developed a robust and sensitive assay for the quantification of intact and defective HIV-1 subtype B and C proviral DNA, making this a suitable tool to monitor the impact of (large-scale) curative interventions. [ABSTRACT FROM AUTHOR]

HIV persists in latently infected cells of patients on antiretroviral therapy (ART). This persistent proviral DNA reservoir is an important predictor of viral rebound upon therapy failure or interruption and forms a major obstacle towards cure. Accurate quantification of the low levels of persisting HIV DNA may aid patient monitoring and cure research. Digital PCR is a promising tool that enables direct absolute quantification with high sensitivity. With recent technological advances, several platforms are available to implement digital PCR in a clinical setting. Here, we compared two digital PCR platforms, the Quantstudio 3D (Life Technologies) and the QX100 (Bio-Rad) with a semi-nested qPCR on serial HIV DNA dilutions and DNA isolated from PBMCs of ART-suppressed patients. All three methods were able to detect target to the lowest levels of 2.5 HIV DNA copies. The QX100 excelled in having the least bias and highest precision, efficiency and quantitative linearity. Patient sample quantifications by the QX100 and semi-nested qPCR were highly agreeable by Bland-Altman analysis (0.01 ± 0.32 log10). Due to the observation of false-positive signals with current digital PCR platforms however, semi-nested qPCR may still be preferred in a setup of low quantity detection to discriminate between presence or absence of HIV DNA. [ABSTRACT FROM AUTHOR]

Available data on the use of maraviroc (MVC) in clinical settings are limited. In this cohort study, the clinical outcomes of HIV-1-infected patients treated with MVC were analysed and the predictive values of different tropism assays were compared. Baseline viral tropism was assessed and compared by phenotypic (Trofile and MT-2) and genotypic assays. Virological and immunological responses were evaluated. In total, 62 predominantly extensively pre-treated patients started MVC [median GSS 2.0 (IQR 2.0–2.5)]. Tropism assays were performed on baseline samples of 58 patients (93.5%). Thirty-two samples (80.0%) were classified as R5 by Trofile, 41 (80.4%) by genotypic tropism test (GTT) and 17 (81.0%) by MT-2. At least two types of tropism assay were performed on samples from 39 patients, whereas in 15 patients all three assays were performed (concordance 84.8–94.1%). Plasma HIV-RNA was <50 copies/mL in 82.1%, 85.0% and 68.8% of patients after 12, 24 and 36 months, respectively; median CD4 cell increase was 199 (IQR 108–283), 291 (IQR 187–413) and 234 (IQR 106–444) cells/μL. The predictive values of different tropism assays were comparably high: at Month 24, 92.9% (Trofile and GTT) and 100.0% (MT-2) of patients had plasma HIV-RNA <50 copies/mL. Three patients stopped MVC treatment because of suspected side effects. Five patients died during follow-up. In this heavily pre-treated cohort, treatment with MVC was well tolerated and resulted in good immunological and virological responses. Results generated by the different tropism assays correlated well with each other and had a high predictive value. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2012; 18: 606-612 Abstract Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with improved prediction of virological response by increasing the detection of X4-tropic variants. Our objective was to evaluate the impact of triplicate genotypic analysis on prediction of co-receptor usage in routine clinical practice. Samples from therapy-naive and therapy-experienced patients were collected for routine tropism testing at three European clinical centres. Viral RNA was isolated from plasma and proviral DNA from peripheral blood mononuclear cells. Gp120-V3 was amplified in a triplicate nested RT-PCR procedure and sequenced. Co-receptor usage was predicted using the Geno2Pheno[coreceptor] algorithm and analysed with a false-positive rate (FPR) of 5.75%, 10%, or an FPR of 20% and according to the current European guidelines on the clinical management of HIV-1 tropism testing. A total of 266 sequences were obtained from 101 patient samples. Discordance in tropism prediction for the triplicates was observed in ten samples using an FPR of 10%. Triplicate testing resulted in a 16.7% increase in X4-predicted samples and to reclassification from R5 to X4 tropism for four cases rendering these patients ineligible for Maraviroc treatment. In conclusion, triplicate genotypic tropism testing increases X4 tropism detection in individual cases, which may prove to be pivotal when CCR5-inhibitor therapy is applied. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the mechanism explaining the persistence of human immunodeficiency virus (HIV) type 1 variants with multiple protease inhibitor (PI)-resistance mutations in the absence of PI therapy. METHODS: Longitudinal genotypic analyses were performed on sequential samples obtained from 2 HIV-1-infected patients who had stopped PI therapy for 4 years. Replication capacity (RC) was determined using recombinant viruses. Subsequently, the effect that changing individual protease mutations back to wild type has on RC was analyzed. RESULTS: We observed prolonged persistence (up to 4 years) of viruses with multiple protease mutations after PI therapy was stopped, despite the fact that the RC of the viruses was severely reduced. Forcing the virus to evolve toward wild type by changing individual protease mutations to wild type was unsuccessful, because all variants displayed a decreased RC in comparison with that of their predecessors. CONCLUSIONS: We propose compensatory fixation as a mechanism for the in vivo persistence of variants with multiple PI-resistance mutations in the absence of PI therapy. Viruses with multiple PI mutations have (partially) compensated for the initial loss in RC. Therefore, reversion of a single mutation causes a (further) reduction in RC and, as a consequence, the route to wild type is blocked. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Abstract: The emergence of drug-resistant viruses is a major issue in the treatment of HIV-1 infections. Quite often these drug-resistant viruses have a reduced replication capacity. A novel assay was developed to study the impact of mutations selected during therapy on viral replication capacity. Two HIV-1 HXB2 reference clones were constructed for this assay based on viral competition experiments, which are identical except for the presence of two silent nucleotide changes in p24 in one of the two clones. Within these two reference clones, three different contiguous deletions were constructed: (I) the C-terminus of Gag and protease, (II) the N-terminus of RT and (III) the C-terminus of Gag and protease together with the N-terminus of RT. Using these reference clones, recombinant viruses were created and viral competition experiments were performed. The proportion of each virus during the competition experiments was determined with a real-time PCR assay based on the two silent nucleotide changes in p24 in one of the two reference clones. With this novel assay it was possible to detect accurately differences in replication capacity due to mutations in the C-terminus of Gag and protease and/or the N-terminus of RT. [Copyright &y& Elsevier]