Emerging airborne contaminants in India : Platinum Group Elements from catalytic converters in motor vehicles

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Applied Geochemistry 75 (2016): 100-106, doi:10.1016/j.apgeochem.2016.10.006.Platinum Group Element (PGE) pollution on the Indian subcontinent is a growing concern because vehicle sales in India have rapidly increased over the last decade, and it is well known that automobile catalytic converters are one of the major source of anthropogenic PGE in the environment. Despite the rapid growth of the Indian automobile industry, the sources and magnitude of PGE contamination in Indian airborne particles are unknown. In this study we report PGE and mercury (Hg) concentrations, as well as osmium isotope ratios (187Os/188Os) of airborne particles (PM10) collected in Kanpur, a large industrial city in India. We estimate that 61±22%, 32±24%, and 7±3% of the total Os fraction are derived from eroding upper continental crust, catalytic converters fitted in the exhaust system of motor vehicles, and fossil fuel combustion, respectively. Only one sample had a ten times higher (~76%) than average contribution from fossil fuel. Unlike Os, Pt is predominantly (84±10%) derived from anthropogenic sources. Platinum Group Element and Hg concentrations are not well correlated. However, the highest concentration of particulate Hg corresponds to the most radiogenic 187Os/188Os isotope ratios (4.6). Our results further indicated that PGE/Ir ratios could be successfully used to quantify the relative proportions of natural and anthropogenic PGE sources in aerosol samples. Since PGE and Hg data on Indian environmental samples are scarce, this study provides an interpretive framework that calls for additional assessments of PGE and Hg concentrations in environmental samples from India.I.S. acknowledges an Indian Institute of Technology Kanpur Initiation Grant that supported this research.2018-10-2

Blood total mercury and methylmercury among pregnant mothers in Charleston, South Carolina, USA

Background Maternal blood total mercury (THg) is a biomarker for prenatal methylmercury (MeHg) exposure. Few studies have quantified both blood THg and MeHg during pregnancy, and few studies have reported longitudinal trends. Objectives We analyzed blood THg and MeHg in a cohort of pregnant mothers in Charleston, South Carolina (n = 83), and investigated whether blood THg or MeHg changed between early and late gestation. Methods THg and MeHg were analyzed in blood samples from early (12 +/- 1.7 weeks) and late (35 +/- 2.2 weeks) gestation. Results Blood %MeHg (of THg) averaged 63% (range: 10-114%) and 61% (range: 12-117%) during early and late gestation, respectively. In unadjusted analyses, blood MeHg decreased from early to late pregnancy (paired t-test, p = 0.04), while THg did not change (paired t-test, p = 0.34). When blood MeHg was normalized by the hematocrit, this decrease was no longer statistically significant (paired t-test, p = 0.09). Conclusions In unadjusted analyses, blood MeHg, but not THg, decreased significantly between early and late gestation; this decrease was due in part to hemodilution. Percent MeHg (of THg) varied by up to one order of magnitude. Results highlight the importance of Hg speciation in maternal blood samples to assess prenatal MeHg exposure

The impact of over 100 years of wildfires on mercury levels and accumulation rates in two lakes in southern California, USA

In southern California, USA, wildfires may be an important source of mercury (Hg) to local watersheds. Hg levels and Hg accumulation rates were investigated in dated sediment cores from two southern California lakes, Big Bear Lake and Crystal Lake, located approximately 40-km apart. Between 1895 and 2006, fires were routinely minimized or suppressed around Big Bear Lake, while fires regularly subsumed the forest surrounding Crystal Lake. Mean Hg concentrations and mean Hg accumulation rates were significantly higher in Crystal Lake sediments compared to Big Bear Lake sediments (Hg levels: Crystal Lake 220 ± 93 ng g−1, Big Bear Lake 92 ± 26 ng g−1; Hg accumulation: Crystal Lake 790 ± 1,200 μg m−2 year−1, Big Bear 240 ± 54 μg m−2 year−1). In Crystal Lake, the ratio between post-1965 and pre-1865 Hg concentrations was 1.1, and several spikes in Hg levels occurred between 1910 and 1985. Given the remote location of the lake, the proximity of fires, and the lack of point sources within the region, these results suggested wildfires (rather than industrial sources) were a continuous source of Hg to Crystal Lake over the last 150 years

Fecal Methylmercury Correlates With Gut Microbiota Taxa in Pacific Walruses (Odobenus rosmarus divergens)

ObjectivesMethylmercury metabolism was investigated in Pacific walruses (Odobenus rosmarus divergens) from St. Lawrence Island, Alaska, United States.MethodsTotal mercury and methylmercury concentrations were measured in fecal samples and paired colon samples (n = 16 walruses). Gut microbiota composition and diversity were determined using 16S rRNA gene sequencing. Associations between fecal and colon mercury and the 24 most prevalent gut microbiota taxa were investigated using linear models.ResultsIn fecal samples, the median values for total mercury, methylmercury, and %methylmercury (of total mercury) were 200 ng/g, 4.7 ng/g, and 2.5%, respectively, while in colon samples, the median values for the same parameters were 28 ng/g, 7.8 ng/g, and 26%, respectively. In fecal samples, methylmercury was negatively correlated with one Bacteroides genus, while members of the Oscillospirales order were positively correlated with both methylmercury and %methylmercury (of total mercury). In colon samples, %methylmercury (of total mercury) was negatively correlated with members of two genera, Romboutsia and Paeniclostridium.ConclusionsMedian %methylmercury (of total mercury) was 10 times higher in the colon compared to the fecal samples, suggesting that methylmercury was able to pass through the colon into systemic circulation. Fecal total mercury and/or methylmercury concentrations in walruses were comparable to some human studies despite differences in seafood consumption rates, suggesting that walruses excreted less mercury. There are no members (at this time) of the Oscillospirales order which are known to contain the genes to methylate mercury, suggesting the source of methylmercury in the gut was from diet and not in vivo methylation

Enrichments of Metals, Including Methylmercury, in Sewage Spills in South Carolina, USA

Exposure to microbial pathogens is the primary concern of sanitary sewer overflows; however, sewage spills may also be a significant source of toxic metals, including methylmercury (MeHg). Between November 2015 and January 2017, after Hurricane Joaquin, surface water samples were collected routinely from three creeks in Columbia, SC. Routine sampling coincided with six sewage spills. Total mercury (THg) and MeHg (unfiltered and filtered) and 32 other metals (filtered) were measured. Compared with surface water samples, THg (unfiltered and filtered), MeHg (unfiltered), and 19 other metals were significantly higher in sewage spills (all log(10)-transformed) (two-tailed t test, p < 0.05 for all, n = 38-42). Toxic weighting factors were applied to 18 metals, including THg and MeHg, in samples collected directly from sewage spills (n = 3-4) and a wastewater outfall (n = 5). On average, sewage was 18.2 and 12.0 times more toxic for THg and MeHg, respectively, and 1.75 times more toxic for all 18 metals, compared to treated effluent from the wastewater outfall. Results suggest sewage spills were a source of inorganic Hg, MeHg, and other metals to the receiving waters and may potentially contribute to water quality impairments

Diffusion of Subsidized ACTs in Accredited Drug Shops in Tanzania: Determinants of Stocking and Characteristics of Early and Late Adopters.

Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers

Prognostic impact of <i>CEBPA </i>mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIP InDel), frameshift InDel or nonsense mutations inducing translational stop (bZIP STOP) or single base-pair missense alterations (bZIP ms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIP InDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIP InDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIP InDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIP InDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIP ms). (Figure presented.)</p

Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist decision-making on reimbursement

<p>Abstract</p> <p>Background</p> <p>XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid + oxaliplatin) have shown similar improvements in survival in patients with metastatic colorectal cancer (MCRC). A US cost-minimization study found that the two regimens had similar costs from a healthcare provider perspective but XELOX had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost-effectiveness study found XELOX had superior cost-effectiveness. This study compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in two oncology departments in Hong Kong.</p> <p>Methods</p> <p>Cost data were collected from the medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4) from two hospitals. Drug costs, outpatient visits, hospital days and investigations were recorded and expressed as cost per patient from the healthcare provider perspective. Estimated travel and time costs were included in a societal perspective analysis. All costs were classed as either scheduled (associated with planned chemotherapy and follow-up) or unscheduled (unplanned visits or admissions and associated tests and medicines). Costs were based on government and hospital sources and expressed in US dollars (US$).</p> <p>Results</p> <p>XELOX patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles) and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The scheduled cost per patient per cycle was$2,046 for XELOX and $2,152 for FOLFOX4, while the unscheduled cost was$240 and $421, respectively. Total treatment cost per patient was$16,609 for XELOX and $23,672 for FOLFOX4; the total cost for FOLFOX4 was 37$17,836 for XELOX and $27,455 for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4 when using full drug regimen costs, incorporating data from a US model with costs and adverse event data from their clinical trial and with the removal of oxaliplatin from both treatment arms. Capecitabine would have to cost around four times its present price in Hong Kong for the total resource cost of treatment with XELOX to equal that of FOLFOX4.</p> <p>Conclusion</p> <p>XELOX costs less than FOLFOX4 for this patient group with MCRC from both the healthcare provider and societal perspectives.</p

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number

Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia

Prognostic impact of CEBPA mutational subgroups in adult AML

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP) or single base-pair missense alterations (bZIPms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms)