Polymer-based drug-eluting stent treatment extends the time to reintervention for patients with symptomatic femoropopliteal artery disease: clinical evidence and potential economic value.

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US $1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames.

Comparative life-cycle sustainability assessment of centralized and decentralized remediation strategies at the city level.

Remediation of contaminated soil at industrial sites has become a challenge and an opportunity for sustainable urban land use, considering the substantial secondary impacts resulting from remediation activities. The design of soil remediation strategies for multi-site remediation from a regional perspective is of great significance for cities with a large number of brownfields. Centralized and decentralized facilities have been studied in different environmental fields, yet limited research has focused on centralized soil remediation, specifically the treatment of contaminated soil from different sites through the construction of shared soil treatment facilities. This study proposes a framework for comparing centralized and decentralized strategies for contaminated soil remediation based on the integration of life-cycle sustainability assessment and multi-objective optimization. With Zhuzhou, an industrial city in China, serving as an example, results show that after optimization, the centralized scenario can reduce total environmental impacts by 25 %-41 %. In addition, the centralized scenario can reduce economic costs by 27 %-39 %, saving up to 176 million USD. The advantages of the centralized soil remediation strategy include: (1) increased use of soil washing, (2) reduced use of off-site disposal, and (3) reduced construction and efficient utilization of soil treatment facilities. In conclusion, the centralized strategy is relatively suitable for cities or areas with a large number of medium or small-sized contaminated sites. The built framework can quantitatively evaluate multiple sites soil remediation at both the city and individual site level, allowing for a straightforward and objective comparison with the optimal remediation design.

Comprehensive assessment of soil and dust heavy metal(loid)s exposure scenarios at residential playgrounds in Beijing, China.

Small playgrounds situated within residential communities are popular recreational areas. However, heavy metal(loid)s (HMs) in soil or equipment dust may pose a public health risk. This study provides a comprehensive assessment of the health risk associated with HMs exposure at residential playgrounds in cities, a field that has not been thoroughly investigated previously. 70 soil and 70 equipment dust samples were collected from 30 urban and 40 suburban playgrounds in Beijing. Results indicated significant enrichment of Cu, As, and Ni in the soil with Enrichment Factors (EFs) >5 from both anthropogenic and lithogenic sources. Correlation analyses showed that the levels of Be, Cr, Mn, Co, Ni in soil and Be, Mn, As, Cd in dust were positively correlated with the distance to the nearest highway, with p-values < 0.01. Enrichment and correlation analyses contributed to a better understanding of the sources and transport pathways of HMs in urban environment. Based on a site-specific Conceptual Site Model (CSM), the carcinogenic risks (CRs) and Hazard Quotients (HQs) were quantified for residents as the ratio of HMs exposure to reference doses. Risk assessment indicated the mean predicted CR for children and adults exposed to soil was 3.75 × 10-6 and 5.29 × 10-6, respectively, while that at dust exposure scenarios was lower, at 2.47 × 10-6 and 3.49 × 10-6, respectively, all of which were at the upper end of U.S. EPA's acceptable criteria of 1 × 10-6 to 1 × 10-4. Among the HMs, As and Ni were identified as the priority control contaminants due to significant contribution to CRs. Furthermore, the spatial distribution revealed an increasing trend in health risk from the urban center to the suburbs. This study emphasizes the need for effective measures to mitigate potential health risk and enhance the safety of recreational areas, particularly for susceptible individuals.

DynSus: Dynamic sustainability assessment in groundwater remediation practice.

Decision-making processes for clean-up of contaminated sites are often highly complex and inherently uncertain. It depends not only on hydrological and biogeochemical site variability, but also on the associated health, environmental, economic, and social impacts of taking, or not taking, action. These variabilities suggest that a dynamic framework is required for promoting sustainable remediation. For this, the decision support system DynSus is presented here for integrating a predeveloped contaminant fate and transport model with a sustainability assessment tool. Implemented within a system dynamics framework, the new tool uses model simulations to provide remediation scenario analysis and handling of uncertainty in various data. DynSus was applied to a site in south Sweden, contaminated with pentachlorophenol (PCP). Simulation scenarios were developed to enable a comparison between alternative remediation strategies and combinations of these. Such comparisons are provided for selected sustainability indicators and remediation performance (in terms of concentration at the recipient). This leads to identifying the most critical variables to ensure that sustainable solutions are chosen. Simulation results indicated that although passive practices, e.g., monitored natural attenuation, were more sustainable at first (5-7 years after beginning remediation measures), they failed to compete with more active practices, e.g., bioremediation, over the entire life cycle of the project (from the beginning of remedial action to achieving the target concentration at the recipient). In addition, statistical tools (clustering and genetic algorithms) were used to further assess the available hydrogeochemical data. Taken together, the results reaffirmed the suitability of the simple analytical framework that was implemented in the contaminant transport model. DynSus outcomes could therefore enable site managers to evaluate different scenarios more quickly and effectively for life cycle sustainability in such a complex and multidimensional problem.

Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2.

The COVID-19 pandemic exposed difficulties in scaling current quantitative PCR (qPCR)-based diagnostic methodologies for large-scale infectious disease testing. Bottlenecks include lengthy multi-step processes for nucleic acid extraction followed by qPCR readouts, which require costly instrumentation and infrastructure, as well as reagent and plastic consumable shortages stemming from supply chain constraints. Here we report an Oil Immersed Lossless Total Analysis System (OIL-TAS), which integrates RNA extraction and detection onto a single device that is simple, rapid, cost effective, and requires minimal supplies and infrastructure to perform. We validated the performance of OIL-TAS using contrived SARS-CoV-2 viral particle samples and clinical nasopharyngeal swab samples. OIL-TAS showed a 93% positive predictive agreement (n = 57) and 100% negative predictive agreement (n = 10) with clinical SARS-CoV-2 qPCR assays in testing clinical samples, highlighting its potential to be a faster, cheaper, and easier-to-deploy alternative for infectious disease testing.

Biochar Aging: Mechanisms, Physicochemical Changes, Assessment, And Implications for Field Applications.

Biochar has triggered a black gold rush in environmental studies as a carbon-rich material with well-developed porous structure and tunable functionality. While much attention has been placed on its apparent ability to store carbon in the ground, immobilize soil pollutants, and improve soil fertility, its temporally evolving in situ performance in these roles must not be overlooked. After field application, various environmental factors, such as temperature variations, precipitation events and microbial activities, can lead to its fragmentation, dissolution, and oxidation, thus causing drastic changes to the physicochemical properties. Direct monitoring of biochar-amended soils can provide good evidence of its temporal evolution, but this requires long-term field trials. Various artificial aging methods, such as chemical oxidation, wet-dry cycling and mineral modification, have therefore been designed to mimic natural aging mechanisms. Here we evaluate the science of biochar aging, critically summarize aging-induced changes to biochar properties, and offer a state-of-the-art for artificial aging simulation approaches. In addition, the implications of biochar aging are also considered regarding its potential development and deployment as a soil amendment. We suggest that for improved simulation and prediction, artificial aging methods must shift from qualitative to quantitative approaches. Furthermore, artificial preaging may serve to synthesize engineered biochars for green and sustainable environmental applications.

Phytoremediation: Climate change resilience and sustainability assessment at a coastal brownfield redevelopment.

Phytoremediation offers a nature based solution (NBS) for contaminated soil remediation; however, its application under a brownfield redevelopment context has not been well studied. Moreover, climate change could impact large numbers of contaminated sites, yet there remains little research on the potential impacts for remediation. This study examined phytoremediation at a brownfield redevelopment in the San Francisco Bay area, where thousands of cleanup sites are vulnerable to rising sea levels. Life cycle assessment (LCA) was used to determine both primary and secondary impacts and the system's resilience to various sea level scenarios and hydroclimatic conditions was investigated. It was found that the phytoremediation project rendered only a small environmental footprint, and was associated with low cost and substantial socioeconomic benefits. For instance, it fitted well with the site redevelopment setting by offering attractive landscape features. Moreover, under a modeled moderate sea level rise scenario, the groundwater hydraulic gradient at the site decreased, which was coupled with greater natural biodegradation and reduced plume migration, and, therefore, lower life cycle impact. There was also minimal increase in the vapor intrusion risk with increased sea level. Overall, phytoremediation at the site was found to be resilient to a moderate sea level rise and other hydroclimatic effects induced by climate change. However, the system performance responded to increasing sea level rise in a non-linear manner. Under a high sea level rise scenario, the system is predicted to perform abruptly worse.

Groundwater depletion and contamination: Spatial distribution of groundwater resources sustainability in China.

China is facing a groundwater depletion and deterioration crisis, culminating from long-term over-exploitation and groundwater contamination. Aggravating factors include population growth, unprecedented urbanization and climate change. Sustainable groundwater management is called for, however, a valid means for a national-scale assessment of groundwater resource sustainability does not currently exist. Here we present a drivers-pressures-states-impact-response (DPSIR) assessment framework. Based on this framework, groundwater sustainability indices for mainland China's 31 provinces and municipalities were derived, with an average score of 59.5 out of 100, ranging from 47.3 for Tianjin to 72.9 for Tibet. We found that due to fewer Drivers and better States, groundwater resources in southern China are far more sustainable than those in the northern and eastern areas. An appraisal of subcategories shed light on the importance of affording attention to externalities such as societal, economic and environmental factors, which are interrelated as complex systems. Based on the assessment findings, implications for policy and decision-making suggestions for sustainable management of China's groundwater resources are put forward.

Strengthening social-environmental management at contaminated sites to bolster Green and Sustainable Remediation via a survey.

The Green and Sustainable Remediation (GSR) movement demands informed, integrated, and holistic management of contaminated sites. As such, GSR may become increasingly relevant in developing countries such as China, where vast areas of contaminated land require clean-up. Among other efforts, the World Bank together with China's Foreign Economic Cooperation Office is facilitating GSR adoption through the development of a guideline on social-environmental management. However, there are no existing studies that have considered how the established remediation industry perceives its effectiveness in addressing the various social-environmental management aspects, or how certain aspects have rooted. Without this information, it may be difficult to guide social-environmental practice forward, or introduce GSR into developing remediation markets with any precision. Therefore, a questionnaire survey of remediation participators was undertaken with principal component analysis (PCA) applied to the data to help group the various aspects. The PCA extracted two components for environmental management, ascribed to: (1) on-site/local impacts; and, (2) widespread impacts, and three social management components, ascribed to: (1) community inclusion; (2) economic gain; and, (3) health, safety, and welfare. It was found that the aspects the industry are most familiar with historically are generally dealt with more effectively than those that have only recently been introduced by the GSR movement. In particular, bolstering the management of widespread environmental impacts and giving greater regard to the economic gain of remediation, may be beneficial. In developing countries, public engagement is often very limited, necessitating improvement in remediation policy and guidance.

Mercury speciation, transformation, and transportation in soils, atmospheric flux, and implications for risk management: A critical review.

Mercury (Hg) is a potentially harmful trace element in the environment and one of the World Health Organization's foremost chemicals of concern. The threat posed by Hg contaminated soils to humans is pervasive, with an estimated 86 Gg of anthropogenic Hg pollution accumulated in surface soils worldwide. This review critically examines both recent advances and remaining knowledge gaps with respect to cycling of mercury in the soil environment, to aid the assessment and management of risks caused by Hg contamination. Included in this review are factors affecting Hg release from soil to the atmosphere, including how rainfall events drive gaseous elemental mercury (GEM) flux from soils of low Hg content, and how ambient conditions such as atmospheric O3 concentration play a significant role. Mercury contaminated soils constitute complex systems where many interdependent factors, including the amount and composition of soil organic matter and clays, oxidized minerals (e.g. Fe oxides), reduced elements (e.g. S2-), as well as soil pH and redox conditions affect Hg forms and transformation. Speciation influences the extent and rate of Hg subsurface transportation, which has often been assumed insignificant. Nano-sized Hg particles as well as soluble Hg complexes play important roles in soil Hg mobility, availability, and methylation. Finally, implications for human health and suggested research directions are put forward, where there is significant potential to improve remedial actions by accounting for Hg speciation and transportation factors.

Assessment of sources of heavy metals in soil and dust at children's playgrounds in Beijing using GIS and multivariate statistical analysis.

Potentially toxic elements such as heavy metals are ubiquitous in the environment. Risk-based environmental management relies upon identifying pollution sources, pathways, and the exposed population. In a Chinese urban setting, many residents live in high-rise buildings without private gardens. Therefore, the main residential risk of exposure to contaminated soils and dusts may be associated with public open spaces. As children are the most vulnerable receptor, playgrounds represent an important yet often overlooked exposure point. The present study assessed plausible sources of heavy metals at children's playgrounds in a representative metropolitan environment. Soil and equipment dust samples were collected from 71 playgrounds across Beijing, which were analyzed for 11 different heavy metals. Principal component analysis (PCA) was used to identify the latent constructs which control heavy metal variability and reflect potential sources. Cluster analysis (CA) was conducted to group sampled locations, which provided further insights on plausible sources. The main factors extracted from the PCA were then subject to geostatistical analysis. The systematic combination of GIS with multivariate statistical analysis proved valuable for elucidating anthropogenic and natural sources. Elevated Be, V, Cr, Mn, Co, Ni, As in playground soils were found to derive mainly from the natural background (spatial autocorrelation = 2 km), while elevated Cu and Pb was attributed to traffic activities (spatial autocorrelation = 17 km), especially along the routes of Beijing's inner ring-roads, the major roads toward the northwest and northeast, and the international airport. These results suggest that heavy metals in playground equipment dust may derive mainly from atmospheric deposition of air pollution of both natural and anthropogenic origin (spatial autocorrelation = 11-13 km). Among them, Be, V, Mn, Co, Cu, As, Pb were attributed to atmospheric pollution deriving from the north of Beijing, brought by the prevailing northern wind in the winter season; whereas, Cr and Ni may possibly be brought from the southeast by the summer season winds. Knowledge of anthropogenic vs. natural origins of heavy metals in playgrounds is critical in assessing health impact and designing policy instruments for metropolitan areas.

Targeting cleanups towards a more sustainable future.

A tension arises between society's disposition to protect people at risk from environmental pollution, and an aversion towards the potential harmful side-effects associated with cleanup activities. Here we explore how setting different cleanup standards may influence some of the environmental, social, and economic side-effects of remediation, and how they can be quantified for incorporation into cleanup target setting; these include (1) secondary environmental impacts, assessed by life cycle assessment (LCA); (2) fatalities and injuries, assessed by actuarial risk analysis; and (3) the cost effectiveness of stringent cleanup standards, assessed by the incremental cost-effectiveness ratio (ICER). We argue that only by using optimal cleanup standards that integrate quantified remediation side-effects with health risk assessment (HRA) can the green and sustainable remediation (GSR) movement maximize its potential. Together, the combined approaches may provide a more holistic management of risks for a more sustainable future.

Environmental and socio-economic sustainability appraisal of contaminated land remediation strategies: A case study at a mega-site in China.

Green and sustainable remediation (GSR) has become a global trend in the contaminated land remediation field. Growing numbers of countries have adopted GSR procedures published in regulatory and/or technical guidance. China is fast becoming one of the largest remediation markets in the world, and is beginning to engage with GSR. Among other efforts, a taskforce is currently developing the first Chinese technical standard on GSR. This paper presents the context positioning and development of a sustainable remediation assessment indicator set for China. This sustainability indicator set was formed based on existing sustainable remediation guidelines and literature. LCA was used to evaluate environmental impacts, and the results combined with social and economic appraisal via MCA. The indicator set was applied to a remediation 'mega-site' in China. The results showed that compared to excavation and landfill, an alternative treatment strategy of soil washing, thermal desorption and S/S brought about relatively less waste generation, better worker safety, and preferable local impacts, leading to higher scores in the environmental and social-economic domains. However, the social-economic scores were limited by a lack of public engagement. The results of the case study have shown that the indicator set is valid, with lessons learnt and suggestions for improvement discussed.

Integrated GIS and multivariate statistical analysis for regional scale assessment of heavy metal soil contamination: A critical review.

Heavy metal soil contamination is associated with potential toxicity to humans or ecotoxicity. Scholars have increasingly used a combination of geographical information science (GIS) with geostatistical and multivariate statistical analysis techniques to examine the spatial distribution of heavy metals in soils at a regional scale. A review of such studies showed that most soil sampling programs were based on grid patterns and composite sampling methodologies. Many programs intended to characterize various soil types and land use types. The most often used sampling depth intervals were 0-0.10 m, or 0-0.20 m, below surface; and the sampling densities used ranged from 0.0004 to 6.1 samples per km2, with a median of 0.4 samples per km2. The most widely used spatial interpolators were inverse distance weighted interpolation and ordinary kriging; and the most often used multivariate statistical analysis techniques were principal component analysis and cluster analysis. The review also identified several determining and correlating factors in heavy metal distribution in soils, including soil type, soil pH, soil organic matter, land use type, Fe, Al, and heavy metal concentrations. The major natural and anthropogenic sources of heavy metals were found to derive from lithogenic origin, roadway and transportation, atmospheric deposition, wastewater and runoff from industrial and mining facilities, fertilizer application, livestock manure, and sewage sludge. This review argues that the full potential of integrated GIS and multivariate statistical analysis for assessing heavy metal distribution in soils on a regional scale has not yet been fully realized. It is proposed that future research be conducted to map multivariate results in GIS to pinpoint specific anthropogenic sources, to analyze temporal trends in addition to spatial patterns, to optimize modeling parameters, and to expand the use of different multivariate analysis tools beyond principal component analysis (PCA) and cluster analysis (CA).

Use of Minimal Residual Disease Assessment to Redefine Induction Failure in Pediatric Acute Lymphoblastic Leukemia.

Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR. Median follow-up was 5 years 9 months. Results Fifty-nine patients (1.9%) had morphologic induction failure with 5-year event-free survival (EFS) of 50.7% (95% CI, 37.4 to 64.0) and 5-year overall survival of 57.7% (95% CI, 44.2 to 71.2). Of these, a small proportion of patients with M2 marrow (6 of 44) and a low EOI MRD level (< 0.01%) had 5-year EFS of 100%. Conversely, among patients with morphologic remission 2.3% (61 of 2,633) had high MRD (≥ 5%) and 5-year EFS of 47.0% (95% CI, 32.9 to 61.1), which was similar to those with morphologic induction failure. Redefining induction failure to include morphologic induction failure and/or MRD ≥ 5% identified 3.9% (120 of 3,133 patients) of the trial cohort with 5-year EFS of 48.0% (95% CI, 39.3 to 58.6). Induction failure (morphologic or MRD ≥ 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking established chromosomal abnormalities (5.6%; 43 of 772 B-other cases). Genetic testing within the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases. Conclusion Integration of EOI MRD level with morphology identifies induction failure more precisely than morphology alone. Prevalence of EBF1-PDGFRB fusions in this group highlights the importance of genetic screening to identify abnormalities that may be targets for novel agents.

Development of a Qualitative Quantitative Polymerase Chain Reaction Test to Identify Patients Failing First-Line Therapy to Non-Nucleotide Reverse Transcriptase Inhibitor.

Antiretroviral therapy (ART) can be compromised by selection of drug resistance strains, which can be promoted by lack of adherence during therapy and drug tolerance, and some of these drug-resistant strains can persist for years as minority populations. The K103N drug resistance mutation is selected by the use of non-nucleotide reverse transcriptase inhibitors, including nevirapine or efavirenz (EFV), used in low-income countries. Here we describe the use of a less expensive qualitative point mutation polymerase chain reaction (PMqPCRK103N) targeting K103N mutation. To validate the use of this methodology, we tested previously sequenced samples from patients treated with highly active ART with viral loads above 2,000 copies/ml and compared the results of our assay with Illumina deep sequencing. Due to its low cost and high specificity, this test is particularly suitable for low-income countries to screen for pretreatment resistance in patients either initiating ART or failing first-line regimens containing EFV.

Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components.

The recent Zika virus outbreak highlights the need for low-cost diagnostics that can be rapidly developed for distribution and use in pandemic regions. Here, we report a pipeline for the rapid design, assembly, and validation of cell-free, paper-based sensors for the detection of the Zika virus RNA genome. By linking isothermal RNA amplification to toehold switch RNA sensors, we detect clinically relevant concentrations of Zika virus sequences and demonstrate specificity against closely related Dengue virus sequences. When coupled with a novel CRISPR/Cas9-based module, our sensors can discriminate between viral strains with single-base resolution. We successfully demonstrate a simple, field-ready sample-processing workflow and detect Zika virus from the plasma of a viremic macaque. Our freeze-dried biomolecular platform resolves important practical limitations to the deployment of molecular diagnostics in the field and demonstrates how synthetic biology can be used to develop diagnostic tools for confronting global health crises. PAPERCLIP.

Renal function after low central venous pressure-assisted liver resection: assessment of 2116 cases.

OBJECTIVES: Low central venous pressure (LCVP)-assisted hepatectomy is associated with decreased blood loss and lower transfusion rates. Concerns about its impact on renal function have prevented widespread application. This study was conducted to review the dynamics of renal function after LCVP-assisted hepatectomy. METHODS: A retrospective analysis of a prospective surgical database was carried out. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The RIFLE (risk-injury-failure-loss-end-stage) criteria were used to define postoperative biochemical acute kidney injury (bAKI). Occurrences of clinically relevant AKI (cAKI) were identified in the study center postoperative database. RESULTS: During the period 2003-2012, 2116 LCVP-assisted hepatectomies were performed. The median patient age was 61 years [interquartile range (IQR): 51-70 years] and 51% of patients were male. The median number of resected segments was two; resections involved from one to four segments. Median estimated blood loss was 300 ml (IQR: 200-600 ml). Rates of morbidity and 90-day mortality were 21% and 2%, respectively. Low baseline eGFR (<90 ml/min) was seen in 84% of patients; 29% of patients had eGFR of <30 ml/min. Postoperative bAKI was seen in 17% (n = 350) of patients. Biochemical AKI with low eGFR was seen in 336 patients, representing 16% of the whole cohort; 13% of patients had been at risk, 2% experienced injury and 1% experienced failure. Kidney function had normalized at discharge in 159 of these patients. Nine patients (<1%) developed postoperative cAKI. CONCLUSIONS: The majority of patients in the study cohort had low baseline eGFR. Biochemical alterations in eGFR are transient in the vast majority of patients after LCVP-assisted hepatectomy and their clinical impact is limited. The present data suggest that clinically relevant renal dysfunction is a very uncommon event in patients undergoing LCVP-assisted liver resection.

Low-cost ultra-wide genotyping using Roche/454 pyrosequencing for surveillance of HIV drug resistance.

BACKGROUND: Great efforts have been made to increase accessibility of HIV antiretroviral therapy (ART) in low and middle-income countries. The threat of wide-scale emergence of drug resistance could severely hamper ART scale-up efforts. Population-based surveillance of transmitted HIV drug resistance ensures the use of appropriate first-line regimens to maximize efficacy of ART programs where drug options are limited. However, traditional HIV genotyping is extremely expensive, providing a cost barrier to wide-scale and frequent HIV drug resistance surveillance. METHODS/RESULTS: We have developed a low-cost laboratory-scale next-generation sequencing-based genotyping method to monitor drug resistance. We designed primers specifically to amplify protease and reverse transcriptase from Brazilian HIV subtypes and developed a multiplexing scheme using multiplex identifier tags to minimize cost while providing more robust data than traditional genotyping techniques. Using this approach, we characterized drug resistance from plasma in 81 HIV infected individuals collected in São Paulo, Brazil. We describe the complexities of analyzing next-generation sequencing data and present a simplified open-source workflow to analyze drug resistance data. From this data, we identified drug resistance mutations in 20% of treatment naïve individuals in our cohort, which is similar to frequencies identified using traditional genotyping in Brazilian patient samples. CONCLUSION: The developed ultra-wide sequencing approach described here allows multiplexing of at least 48 patient samples per sequencing run, 4 times more than the current genotyping method. This method is also 4-fold more sensitive (5% minimal detection frequency vs. 20%) at a cost 3-5× less than the traditional Sanger-based genotyping method. Lastly, by using a benchtop next-generation sequencer (Roche/454 GS Junior), this approach can be more easily implemented in low-resource settings. This data provides proof-of-concept that next-generation HIV drug resistance genotyping is a feasible and low-cost alternative to current genotyping methods and may be particularly beneficial for in-country surveillance of transmitted drug resistance.