Sunt verba rerum: the pragmatic life of words.

Pragmatics is not about language as such, viewed in isolation, but about words as they are being used. And words are never things, pure objects; words have their history and lives: their story is the story of their users. Pragmatic thinking focuses not just on what 'is' there (the 'essentialist' method of linguistics), but on how what 'is' there, 'got' there, and what it 'does' there, in a 'functionalist' approach, characteristic of pragmatics. Such a functional approach relies heavily on the processes that are material in creating the conditions for words to be used in a particular way: both those processes we normally call 'historical' (the history of what has been) and those that are characteristic for what happens in our own times: the pragmatic life of words. I will illustrate these reflections by focusing on a series of well-known linguistic phenomena, first of all the historical 'emptying' of content known as 'semantic bleaching', and second the transformation of the ways words function, commonly known under the name of 'grammaticalization' or 'grammaticization'. To better understand these processes, I will first focus on what I call the 'historical bias' of structuralist linguistics, including a brief discussion of issues having to do with language development and how linguists and historians traditionally have tried to deal with this.

Child Intelligence and Reductions in Water Arsenic and Manganese: A Two-Year Follow-up Study in Bangladesh.

BACKGROUND: Arsenic (As) exposure from drinking water is associated with modest intellectual deficits in childhood. It is not known whether reducing exposure is associated with improved intelligence. OBJECTIVE: We aimed to determine whether reducing As exposure is associated with improved child intellectual outcomes. METHODS: Three hundred three 10-year-old children drinking from household wells with a wide range of As concentrations were enrolled at baseline. In the subsequent year, deep community wells, low in As, were installed in villages of children whose original wells had high water As (WAs ≥ 50 µg/L). For 296 children, intelligence was assessed by WISC-IV (Wechsler Intelligence Scale for Children, 4th ed.), with a version modified for the study population, at baseline and approximately 2 years later; analyses considered standardized scores for both Full Scale IQ and Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed Indices. Creatinine-adjusted urinary arsenic (UAs/Cr), blood As (BAs), and blood manganese (BMn) were assessed at both times. RESULTS: UAs/Cr concentrations declined significantly by follow-up for both the high (≥ 50 µg/L) and low (< 50 µg/L) WAs subgroups. At baseline, adjusting for maternal age and intelligence, plasma ferritin, head circumference, home environment quality, school grade, and BMn, UAs/Cr was significantly negatively associated with Full Scale IQ, and with all Index scores (except Processing Speed). After adjustment for baseline Working Memory scores and school grade, each 100-µg/g reduction in UAs/Cr from baseline to follow-up was associated with a 0.91 point increase in Working Memory (95% CI: 0.14, 1.67). The change in UAs/Cr across follow-up was not significantly associated with changes in Full Scale IQ or Index scores. CONCLUSIONS: Installation of deep, low-As community wells lowered UAs, BAs, and BMn. A greater decrease in UAs/Cr was associated with greater improvements in Working Memory scores, but not with a greater improvement in Full Scale IQ. CITATION: Wasserman GA, Liu X, Parvez F, Factor-Litvak P, Kline J, Siddique AB, Shahriar H, Uddin MN, van Geen A, Mey JL, Balac O, Graziano JH. 2016. Child intelligence and reductions in water arsenic and manganese: a two-year follow-up study in Bangladesh. Environ Health Perspect 124:1114-1120; http://dx.doi.org/10.1289/ehp.1509974.

Evaluation of an Elementary School-based Educational Intervention for Reducing Arsenic Exposure in Bangladesh.

BACKGROUND: Chronic exposure to well water arsenic (As) remains a major rural health challenge in Bangladesh and some other developing countries. Many mitigation programs have been implemented to reduce As exposure, although evaluation studies for these efforts are rare in the literature. OBJECTIVES: In this study we estimated associations between a school-based intervention and various outcome measures of As mitigation. METHODS: We recruited 840 children from 14 elementary schools in Araihazar, Bangladesh. Teachers from 7 schools were trained on an As education curriculum, whereas the remaining 7 schools without any training formed the control group. Surveys, knowledge tests, and well-water testing were conducted on 773 children both at baseline and postintervention follow-up. Urine samples were collected from 210 children from 4 intervention schools and the same number of children from 4 control schools. One low-As (< 10 µg/L) community well in each study village was ensured during an 18-month intervention period. RESULTS: After adjustment for the availability of low-As wells and other sociodemographic confounders, children receiving the intervention were five times more likely to switch from high- to low-As wells (p < 0.001). We also observed a significant decline of urinary arsenic (UAs) (p = < 0.001) (estimated ß = -214.9; 95% CI: -301.1, -128.7 µg/g creatinine) among the children who were initially drinking from high-As wells (> Bangladesh standard of 50 µg/L) and significantly improved As knowledge attributable to the intervention after controlling for potential confounders. CONCLUSIONS: These findings offer strong evidence that school-based intervention can effectively reduce As exposure in Bangladesh by motivating teachers, children, and parents.

Folic Acid and Creatine as Therapeutic Approaches to Lower Blood Arsenic: A Randomized Controlled Trial.

BACKGROUND: The World Health Organization estimates that > 140 million people worldwide are exposed to arsenic (As)-contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/supplemental creatine. OBJECTIVES: Our aim was to determine whether 400 or 800 µg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. METHODS: We conducted a clinical trial in which 622 participants were randomized to receive 400 µg FA, 800 µg FA, 3 g creatine, 3 g creatine+400 µg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. RESULTS: Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-µg FA group exceeded that of the placebo group (weeks 1-12: ß= -0.09, 95% CI: -0.18, -0.01; weeks 13-24: FA continued: ß= -0.12, 95% CI: -0.24, -0.00; FA switched to placebo: ß= -0.14, 95% CI: -0.26, -0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. CONCLUSIONS: In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 µg (but not 400 µg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles.

A dose-response study of arsenic exposure and markers of oxidative damage in Bangladesh.

OBJECTIVE: To evaluate the dose-response relationship between arsenic (As) exposure and markers of oxidative damage in Bangladeshi adults. METHODS: We recruited 378 participants drinking water from wells assigned to five water As exposure categories; the distribution of subjects was as follows: (1) less than 10 µg/L (n=76); (2) 10 to 100 µg/L (n=104); (3) 101 to 200 µg/L (n=86); (4) 201 to 300 µg/L (n=67); and (5) more than 300 µg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8-oxo-2'-deoxyguanosine and plasma protein carbonyls were measured to assess oxidative damage. RESULTS: None of our measures of As exposure were significantly associated with protein carbonyl or 8-oxo-2'-deoxyguanosine levels. CONCLUSIONS: We found no evidence to support a significant relationship between long-term exposure to As-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults.

A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren.

BACKGROUND: In recent studies in Bangladesh and elsewhere, exposure to arsenic (As) via drinking water is negatively associated with performance-related aspects of child intelligence (e.g., Perceptual Reasoning, Working Memory) after adjustment for social factors. Because findings are not easily generalizable to the US, we examine this relation in a US population. METHODS: In 272 children in grades 3-5 from three Maine school districts, we examine associations between drinking water As (WAs) and intelligence (WISC-IV). RESULTS: On average, children had resided in their current home for 7.3 years (approximately 75% of their lives). In unadjusted analyses, household well WAs is associated with decreased scores on most WISC-IV Indices. With adjustment for maternal IQ and education, HOME environment, school district and number of siblings, WAs remains significantly negatively associated with Full Scale IQ and Perceptual Reasoning, Working Memory and Verbal Comprehension scores. Compared to those with WAs < 5 µg/L, exposure to WAs ≥ 5 µg/L was associated with reductions of approximately 5-6 points in both Full Scale IQ (p < 0.01) and most Index scores (Perceptual Reasoning, Working Memory, Verbal Comprehension, all p's < 0.05). Both maternal IQ and education were associated with lower levels of WAs, possibly reflecting behaviors (e.g., water filters, residential choice) limiting exposure. Both WAs and maternal measures were associated with school district. CONCLUSIONS: The magnitude of the association between WAs and child IQ raises the possibility that levels of WAs ≥ 5 µg/L, levels that are not uncommon in the United States, pose a threat to child development.

Confirmation of elevated arsenic levels in groundwater of Myanmar.

Millions of villagers across South and Southeast Asia are exposed to toxic levels of arsenic (As) by drinking well water. In order to confirm the field-kit results that Myanmar is also affected, a total of 55 wells were tested in the field in January 2013 and sampled for laboratory analysis across seven villages spanning a range of As contamination in the lower Ayeyarwady basin. Elevated concentrations of As (50-630 µg/L) were measured in wells up to 60 m deep and associated with high levels of Fe (up to 21 mg/L) and low concentrations of SO4 (<0.05 mg/L). Concentrations of As <10 µg/L were measured in some shallow (<30 m) grey sands and in both shallow and deep orange sands. These results indicate that the main mechanism of As release to groundwater in Myanmar is the reductive dissolution of Fe oxyhydroxides, as in the neighboring Bengal, Mekong, and Red River basins. Concentrations of As in groundwater of Myanmar are therefore unlikely to change rapidly over time and switching to existing low-As wells is a viable way of reducing exposure in the short term. However, only 17 of the 55 well owners interviewed correctly recalled the status of their well despite extensive testing in the region. A renewed effort is thus needed to test existing wells and new wells that continue to be installed and to communicate the health risks of exposure to As for infants, children, and adults.

Comparison of two blanket surveys of arsenic in tubewells conducted 12 years apart in a 25 km(2) area of Bangladesh.

The arsenic (As) content of groundwater pumped from all tubewells within 61 contiguous villages of Araihazar, Bangladesh, was determined a first time in 2000-01 with laboratory measurements and a second time in 2012-13 using the ITS Arsenic Econo-Quick kit. The two surveys indicate that the total number of tubewells within the area almost doubled from 5560 to 10,879 over 12 years. The evolution of the distribution of well ages between the two surveys is consistent with a simple model that combines an annual increase of 42 wells/year in the rate of installations within the 61 villages starting in 1980 and a 7%/year rate of abandonment of wells as a function of well age. Colored placards were posted on each pumphead in 2012-13 on the basis of the kit results relative to the WHO guideline for As and the Bangladesh standard for As in drinking water: blue for As≤10 µg/L, green>10-50 µg/L, and red: >50 µg/L. According to quality-control samples collected from 502 tubewells for comparing the kit results with laboratory measurements, not a single well labeled blue in 2012-13 should have been labeled red and vice-versa. Field-kit testing in 2012-13 did not change the status of wells relative to the Bangladesh standard of 876 (87%) out of 1007 wells with a placard based on laboratory measurements in 2000-01 still attached to the pumphead. The high proportion of tubewells believed by households to be unsafe (66% out of 2041) that were still used for drinking and cooking in 2012-13 underlines the need for more widespread testing to identify low-As wells as an alternative source of drinking water.

Retardation of arsenic transport through a Pleistocene aquifer.

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic. Holocene aquifers are the source of widespread arsenic poisoning across the region. In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16-20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport.

A dose-response study of arsenic exposure and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults.

BACKGROUND: Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation. OBJECTIVE: The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water. METHODS: Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [3H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation. RESULTS: Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-µg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures. CONCLUSIONS: These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications.

Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults.

Oxidative stress and DNA methylation are metabolically linked through the relationship between one-carbon metabolism and the transsulfuration pathway, but possible modulating effects of oxidative stress on DNA methylation have not been extensively studied in humans. Enzymes involved in DNA methylation, including DNA methyltransferases and histone deacetylases, may show altered activity under oxidized cellular conditions. Additionally, in vitro studies suggest that glutathione (GSH) depletion leads to global DNA hypomethylation, possibly through the depletion of S-adenosylmethionine (SAM). We tested the hypothesis that a more oxidized blood GSH redox status is associated with decreased global peripheral blood mononuclear cell (PBMC) DNA methylation in a sample of Bangladeshi adults. Global PBMC DNA methylation and whole blood GSH, glutathione disulfide (GSSG), and SAM concentrations were measured in 320 adults. DNA methylation was measured by using the [ (3)H]-methyl incorporation assay; values are inversely related to global DNA methylation. Whole blood GSH redox status (Eh) was calculated using the Nernst equation. We found that a more oxidized blood GSH Eh was associated with decreased global DNA methylation (B ± SE, 271 ± 103, p = 0.009). Blood SAM and blood GSH were associated with global DNA methylation, but these relationships did not achieve statistical significance. Our findings support the hypothesis that a more oxidized blood GSH redox status is associated with decreased global methylation of PBMC DNA. Furthermore, blood SAM does not appear to mediate this association. Future research should explore mechanisms through which cellular redox might influence global DNA methylation.

Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in Bangladeshi adults.

BACKGROUND: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys. OBJECTIVES: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment). METHODS: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: < 10 (n = 76), 10-100 (n = 104), 101-200 (n = 86), 201-300 (n = 67), and > 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC. RESULTS: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, -25.4 µmol/L; 95% CI: -45.3, -5.31) and plasma CySS (mean change, -3.00 µmol/L; 95% CI: -4.61, -1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys. CONCLUSIONS: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine.

Evaluation of an arsenic test kit for rapid well screening in Bangladesh.

Exposure to arsenic in groundwater via drinking remains unabated for millions of villagers in Bangladesh. Since a blanket testing campaign using test kits almost a decade ago, millions of new wells have been installed but not tested; thus affordable testing is needed. The performance of the Arsenic Econo-Quick (EQ) kit was evaluated by blindly testing 123 wells in Bangladesh and comparing with laboratory measurements; 65 wells were tested twice. A subset of the same 123 wells was also tested using the Hach EZ kit in the field and the Digital Arsenator in the laboratory in Bangladesh. The EQ kit correctly determined the status of 110 (89%) and 113 (92%) out of 123 wells relative to the WHO guideline (10 µg/L) and the Bangladesh standard (50 µg/L), respectively. Relative to the WHO guideline, all misclassifications were underestimates for wells containing between >10 and 27 µg/L As. Relative to the Bangladesh As standard, over- and underestimates were evenly distributed. Given its short reaction time of 10 min relative to the Hach EZ and its lower cost compared to the Arsenator, the EQ kit appears to have several advantages for well testing in Bangladesh and elsewhere.

Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers.

The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln µg/L) and urinary arsenic (ln µg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.

Impact on arsenic exposure of a growing proportion of untested wells in Bangladesh.

BACKGROUND: In many areas of Bangladesh, it has been more than six years since a national campaign to test tubewells for arsenic (As) was conducted. Many households therefore draw their water for drinking and cooking from untested wells. METHODS: A household drinking water survey of 6646 households was conducted in Singair upazilla of Bangladesh. A subset of 795 untested wells used by 1000 randomly selected households was tested in the field by trained village workers with the Hach EZ kit, using an extended reaction time of 40 min, and in the laboratory by high-resolution inductively-coupled plasma-mass spectrometry (HR ICP-MS). RESULTS: The household survey shows that more than 80% of the wells installed since the national testing campaign in this area were untested. Less than 13% of the households with untested wells knew where a low-As well was located near their home. Village workers using the Hach EZ kit underestimated the As content of only 4 out of 795 wells relative to the Bangladesh standard. However, the As content of 168 wells was overestimated relative to the same threshold. CONCLUSION: There is a growing need for testing tubewells in areas of Bangladesh where As concentrations in groundwater are elevated. This could be achieved by village workers trained to use a reliable field kit. Such an effort would result in a considerable drop in As exposure as it increases the opportunities for well switching by households.

Arsenic exposure and motor function among children in Bangladesh.

BACKGROUND: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children's intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function. METHODS: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8-11 years of age. We measured As and Mn concentrations in drinking water, blood, urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales-fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility-which can be summarized with a total motor composite score (TMC). RESULTS: Log-transformed blood As was associated with decreases in TMC [ß = -3.63; 95% confidence interval (CI): -6.72, -0.54; p < 0.01], FMC (ß = -1.68; 95% CI: -3.19, -0.18; p < 0.05), and BC (ß = -1.61; 95% CI: -2.72, -0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother's intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (ß = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (ß = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (ß = 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function. CONCLUSION: Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children.

Fecal contamination of shallow tubewells in Bangladesh inversely related to arsenic.

The health risks of As exposure due to the installation of millions of shallow tubewells in the Bengal Basin are known, but fecal contamination of shallow aquifers has not systematically been examined. This could be a source of concern in densely populated areas with poor sanitation because the hydraulic travel time from surface water bodies to shallow wells that are low in As was previously shown to be considerably shorter than for shallow wells that are high in As. In this study, 125 tubewells 6-36 m deep were sampled in duplicate for 18 months to quantify the presence of the fecal indicator Escherichia coli. On any given month, E. coli was detected at levels exceeding 1 most probable number per 100 mL in 19-64% of all shallow tubewells, with a higher proportion typically following periods of heavy rainfall. The frequency of E. coli detection averaged over a year was found to increase with population surrounding a well and decrease with the As content of a well, most likely because of downward transport of E. coli associated with local recharge. The health implications of higher fecal contamination of shallow tubewells, to which millions of households in Bangladesh have switched in order to reduce their exposure to As, need to be evaluated.