Concerns about quadrupole ICP-MS lead isotopic data and interpretations in the environment and health fields

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in International Journal of Environmental Research and Public Health 15 (2018): 723, doi:10.3390/ijerph15040723.There has been a massive increase in recent years of the use of lead (Pb) isotopes in attempts to better understand sources and pathways of Pb in the environment and in man or experimental animals. Unfortunately, there have been many cases where the quality of the isotopic data, especially that obtained by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), are questionable, resulting in questionable identification of potential sources, which, in turn, impacts study interpretation and conclusions. We present several cases where the isotopic data have compromised interpretation because of the use of only the major isotopes 208Pb/206Pb and 207Pb/206Pb, or their graphing in other combinations. We also present some examples comparing high precision data from thermal ionization (TIMS) or multi-collector plasma mass spectrometry (MC-ICP-MS) to illustrate the deficiency in the Q-ICP-MS data. In addition, we present cases where Pb isotopic ratios measured on Q-ICP-MS are virtually impossible for terrestrial samples. We also evaluate the Pb isotopic data for rat studies, which had concluded that Pb isotopic fractionation occurs between different organs and suggest that this notion of biological fractionation of Pb as an explanation for isotopic differences is not valid. Overall, the brief review of these case studies shows that Q-ICP-MS as commonly practiced is not a suitable technique for precise and accurate Pb isotopic analysis in the environment and health field

87Sr/86Sr and 14C evidence for peccary (Tayassuidae) introduction challenges accepted historical interpretation of the 1657 Ligon map of Barbados

Contemporary West Indian biodiversity has been shaped by two millennia of non-native species introductions. Understanding the dynamics of this process and its legacy across extended temporal and spatial scales requires accurate knowledge of introduction timing and the species involved. Richard Ligon’s 17th century account and celebrated map of early colonial Barbados records the translocation of several Old World species to the island in the post-contact era, including pigs (Sus scrofa) believed to have been released by passing sailors the century prior. Here we challenge this long-accepted historical narrative, presenting evidence that Ligon’s “pigs” were in fact peccaries, a New World continental mammal often confused with wild boars. We document the first recorded instance of non-native peccary (Tayassuidae) on Barbados based on a securely identified mandibular specimen from a historic archaeological context. Results of specimen 87Sr/86Sr and AMS radiocarbon assays, along with newly reported data from Sr isotope environmental analyses, indicate a local origin dating to AD 1645–1670/1780–1800. These data support the presence of living peccary on Barbados some time during the first 175 years of English settlement, which, based on review of historical and archaeological data, most likely arises from 16th century peccary introduction from the Guianas/Trinidad by the Spanish or Portuguese. We argue dimorphic representations of “pigs” on Ligon’s map reflect the co-occurrence of peccary and European domestic swine on historic Barbados. Our findings overturn conventional history and provide greater taxonomic and chronological resolution for Caribbean bioinvasion studies, helping to refine our understanding of potential ecological impacts. In addition, the new bioavailable 87Sr/86Sr data for Barbados reported here advance current efforts toward mapping the Caribbean Sr isoscape

Pre-Columbian lead pollution from Native American galena processing and land use in the midcontinental United States

The presence and sources of pre-Columbian (before 1492 CE) lead (Pb) pollution in the midcontinental United States were investigated using geochemical and Pb isotope analyses on sediment cores recovered from Avery Lake, a floodplain lake located directly adjacent to the Kincaid Mounds archaeological site on the lower Ohio River, Illinois. Geochemical results indicate the presence of Pb pollution during the Baumer (300 BCE to 300 CE) and Mississippian (1150–1450 CE) occupations, and since the 1800s. Pb isotope results link Mississippian Pb pollution to the processing and use of galena primarily from southeastern and/or central Missouri, and to a lesser extent the upper Mississippi River valley, with ∼1.5 t (metric tons) of galena-derived Pb deposited in Avery Lake during this time. Pb pollution during the Baumer phase, equating to ∼0.4 t of Pb, was not accompanied by a Pb isotope excursion and most likely originated from local biomass burning. These results provide new information about the environmental impacts associated with pre-Columbian Native Americans’ interaction with and utilization of their landscape and its resources

Evidence for Patterns of Selective Urban Migration in the Greater Indus Valley (2600-1900 BC): A Lead and Strontium Isotope Mortuary Analysis

Just as modern nation-states struggle to manage the cultural and economic impacts of migration, ancient civilizations dealt with similar external pressures and set policies to regulate people’s movements. In one of the earliest urban societies, the Indus Civilization, mechanisms linking city populations to hinterland groups remain enigmatic in the absence of written documents. However, isotopic data from human tooth enamel associated with Harappa Phase (2600-1900 BC) cemetery burials at Harappa (Pakistan) and Farmana (India) provide individual biogeochemical life histories of migration. Strontium and lead isotope ratios allow us to reinterpret the Indus tradition of cemetery inhumation as part of a specific and highly regulated institution of migration. Intra-individual isotopic shifts are consistent with immigration from resource-rich hinterlands during childhood. Furthermore, mortuary populations formed over hundreds of years and composed almost entirely of first-generation immigrants suggest that inhumation was the final step in a process linking certain urban Indus communities to diverse hinterland groups. Additional multi disciplinary analyses are warranted to confirm inferred patterns of Indus mobility, but the available isotopic data suggest that efforts to classify and regulate human movement in the ancient Indus region likely helped structure socioeconomic integration across an ethnically diverse landscape

Advanced Age Is Associated with Iron Dyshomeostasis and Mitochondrial DNA Damage in Human Skeletal Muscle

Whether disruption of iron metabolism is implicated in human muscle aging is presently unclear. We explored the relationship among iron metabolism, muscle mitochondrial homeostasis, inflammation, and physical function in older adults and young controls. Eleven young and 23 older men and women were included. Older adults were classified into high-functioning (HF) and low-functioning (LF) groups according to their Short Physical Performance Battery score. Vastus lateralis muscle biopsies were assayed for total iron content, expression of 8-oxoguanine and DNA glycosylase (OGG1), 3-nitrotyrosine (3-NT) levels, and mitochondrial DNA (mtDNA) content and damage. Circulating ferritin and hepcidin levels were also quantified. Muscle iron levels were greater in the old group. Protein expression of transferrin receptor 1, Zrt-Irt-like protein (ZIP) 8, and ZIP14 were lower in old participants. Circulating levels of ferritin, hepcidin, interleukin 6 (IL6), and C-reactive protein were higher in the old group. Old participants showed lower mtDNA content and greater mtDNA damage. OGG1 protein expression declined with age, whereas 3-NT levels were greater in old participants. Finally, a negative correlation was determined between ZIP14 expression and circulating IL6 levels in LF older adults. None of assayed parameters differed between HF and LF participants. Our findings suggest that muscle iron homeostasis is altered in old age, which might contribute to loss of mtDNA stability. Muscle iron metabolism may therefore represent a target for interventions against muscle aging

The dead shall be raised : Multidisciplinary analysis of human skeletons reveals complexity in 19th century immigrant socioeconomic history and identity in New Haven, Connecticut

In July 2011, renovations to Yale-New Haven Hospital inadvertently exposed the cemetery of Christ Church, New Haven, Connecticut’s first Catholic cemetery. While this cemetery was active between 1833 and 1851, both the church and its cemetery disappeared from public records, making the discovery serendipitous. Four relatively well-preserved adult skeletons were recovered with few artifacts. All four individuals show indicators of manual labor, health and disease stressors, and dental health issues. Two show indicators of trauma, with the possibility of judicial hanging in one individual. Musculoskeletal markings are consistent with physical stress, and two individuals have arthritic indicators of repetitive movement/specialized activities. Radiographic analyses show osteopenia, healed trauma, and other pathologies in several individuals. Dental calculus analysis did not identify any tuberculosis indicators, despite osteological markers. Isotopic analyses of teeth indicate that all four were likely recent immigrants to the Northeastern United States. Nuclear and mitochondrial DNA were recovered from three individuals, and these analyses identified ancestry, hair/eye color, and relatedness. Genetic and isotopic results upended our initial ancestry assessment based on burial context alone. These individuals provide biocultural evidence of New Haven’s Industrial Revolution and the plasticity of ethnic and religious identity in the immigrant experience. Their recovery and the multifaceted analyses described here illuminate a previously undescribed part of the city’s rich history. The collective expertise of biological, geochemical, archaeological, and historical researchers interprets socioeconomic and cultural identity better than any one could alone. Our combined efforts changed our initial assumptions of a poor urban Catholic cemetery’s membership, and provide a template for future discoveries and analyses

Altered Expression of Mitoferrin and Frataxin, Larger Labile Iron Pool and Greater Mitochondrial DNA Damage in the Skeletal Muscle of Older Adults

Mitochondrial dysfunction and iron (Fe) dyshomeostasis are invoked among the mechanisms contributing to muscle aging, possibly via a detrimental mitochondrial-iron feed-forward loop. We quantified the labile Fe pool, Fe isotopes, and the expression of mitochondrial Fe handling proteins in muscle biopsies obtained from young and older adults. The expression of key proteins of mitochondrial quality control (MQC) and the abundance of the mitochondrial DNA common deletion (mtDNA4977) were also assessed. An inverse association was found between total Fe and the heavier Fe isotope (56Fe), indicating an increase in labile Fe abundance in cells with greater Fe content. The highest levels of labile Fe were detected in old participants with a Short Physical Performance Battery (SPPB) score 64 7 (low-functioning, LF). Protein levels of mitoferrin and frataxin were, respectively, higher and lower in the LF group relative to young participants and older adults with SPPB scores 65 11 (high-functioning, HF). The mtDNA4977 relative abundance was greater in old than in young participants, regardless of SPPB category. Higher protein levels of Pink1 were detected in LF participants compared with young and HF groups. Finally, the ratio between lipidated and non-lipidated microtubule-associated protein 1A/1B-light chain 3 (i.e., LC3B II/I), as well as p62 protein expression was lower in old participants regardless of SPPB scores. Our findings indicate that cellular and mitochondrial Fe homeostasis is perturbed in the aged muscle (especially in LF older adults), as reflected by altered levels of mitoferrin and frataxin, which, together with MQC derangements, might contribute to loss of mtDNA stability

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The Pb isotopic record of historical to modern human lead exposure

Human teeth and bones incorporate trace amounts of lead (Pb) from the local environment during growth and remodeling. Anthropogenic activities have caused changes in the natural Pb isotopic background since historical times and this is reflected in the Pb isotopes of historical European teeth. Lead mining and use increased exponentially during the last century and the isotopic compositions of modern human teeth reflect the modern anthropogenic Pb. USA teeth show the most radiogenic Pb and Australian teeth show the least radiogenic Pb, a result of different Pb ores used in the two regions. During the last century the Australian Pb was exported to Europe, Asia, South America, and Africa, resulting in swamping of the local environmental Pb signal by the imported Pb. As a result, the modern human teeth in Europe show a significant drop to lower isotopic values compared with historical times. Similarly, modern human teeth in other regions of the world show similar Pb isotopic ratios to modern European teeth reflecting the Pb imports. The specific pattern of human Pb exposure allows us to use the Pb isotopic signal recorded in the skeleton as a geo-referencing tool. As historical European teeth show a distinct Pb signal, we can identify early European skeletal remains in the New World and likely elsewhere. In modern forensic investigations we can discriminate to some extent Eastern Europeans from Western and Northern Europeans. Australians can be identified to some extent in any region in the world, although there is some overlap with Western European individuals. Lead isotopes can be used to easily identify foreigners in the USA, as modern USA teeth are distinct from any other region of the world. By analogy, USA individuals can be identified virtually in any other region of the world.10 page(s