Pooling samples for "top-down" molecular exposomics research: the methodology.

BACKGROUND: Exposomics is the cutting-edge concept of screening the environmental risk factors for disease. In the novel "top-down" approach, we estimate the molecular exposome by measuring all body fluid analytes in a case-controlled study. However, to detect diverse pollutants, a sufficient sample size and multiple analytical methods are required. This may lead to dramatically increased costs and research workload. METHODS: To help reduce complexity, we suggest a sample pooling strategy along with a scheme for combining both general unknown or multi-targeted screening with targeted analysis. The sample pooling method was tested using computer simulations. RESULTS: By comprehensively analysis of pooled samples, it is possible to identify environmental risk factors. Factors are initially screened in the pooled case and control population samples, then in the randomized grouped and pooled case and control subpopulation samples. In the sample grouping, five or more pools were suggested for groups having 30 individuals per pool. CONCLUSIONS: This study suggests that sample pooling is a useful strategy for exposomics research, which provides a hypothesis-free method for pollutant risk screening.

CombiSimilarity, an innovative method to compare environmental and health data sets with different attribute sizes example: eighteen Organochlorine Pesticides in soil and human breast milk samples.

Human health and the health of the environment have entwined. In this paper we underpin this position by presenting a modeling approach named CombiSimilarity, which has been developed by the first author in the software tool PyHasse comprising a wide variety of partial ordering tools. A case study of 18 Organochlorine Pesticides (OCPs) detected in soil as well as in human breast milk samples in the Taurus Mountains in Turkey is carried out. Seven soil samples and 44 breast milk samples were measured. We seek to answer the question whether the contamination pattern in breast milk is associated with the contamination pattern in soil by studying the mutual quantitative relationships of the chemicals involved. We could demonstrate that there is a similarity with respect to the concentration profiles between the soil and breast milk pollution. Therefore the hypothesis may be formulated that the concentrations of chemicals in the milk samples are strongly related to the soil contamination. This supports the concept that soil could be a surrogate for human exposure at background locations.

Increased sex ratio in Russia and Cuba after Chernobyl: a radiological hypothesis.

BACKGROUND: The ratio of male to female offspring at birth may be a simple and non-invasive way to monitor the reproductive health of a population. Except in societies where selective abortion skews the sex ratio, approximately 105 boys are born for every 100 girls. Generally, the human sex ratio at birth is remarkably constant in large populations. After the Chernobyl nuclear power plant accident in April 1986, a long lasting significant elevation in the sex ratio has been found in Russia, i.e. more boys or fewer girls compared to expectation were born. Recently, also for Cuba an escalated sex ratio from 1987 onward has been documented and discussed in the scientific literature. PRESENTATION OF THE HYPOTHESIS: By the end of the eighties of the last century in Cuba as much as about 60% of the food imports were provided by the former Soviet Union. Due to its difficult economic situation, Cuba had neither the necessary insight nor the political strength to circumvent the detrimental genetic effects of imported radioactively contaminated foodstuffs after Chernobyl. We propose that the long term stable sex ratio increase in Cuba is essentially due to ionizing radiation. TESTING OF THE HYPOTHESIS: A synoptic trend analysis of Russian and Cuban annual sex ratios discloses upward jumps in 1987. The estimated jump height from 1986 to 1987 in Russia measures 0.51% with a 95% confidence interval (0.28, 0.75), p value < 0.0001. In Cuba the estimated jump height measures 2.99% (2.39, 3.60), p value < 0.0001. The hypothesis may be tested by reconstruction of imports from the world markets to Cuba and by radiological analyses of remains in Cuba for Cs-137 and Sr-90. IMPLICATIONS OF THE HYPOTHESIS: If the evidence for the hypothesis is strengthened, there is potential to learn about genetic radiation risks and to prevent similar effects in present and future exposure situations.

Evaluation of organochlorine pesticides in breast milk samples in Turkey applying features of the partial order technique.

Exposure data to organochlorine pesticides (OCPs) of mothers' breast milk samples were measured in different locations in the Taurus Mountains/Turkey. Villages at five altitudes were looked upon. The data analysis method applied is the Hasse diagram technique, based on Discrete Mathematics. For each of the five regions, one Hasse diagram was calculated and showed the same maximal object, namely, p-p'-Dichlorodiphenyldichloroethane (DDE). In a further data investigation step, we performed the similarity analyses of the locations in order to quantify the similarities and incomparabilities. It was revealed that no correlation exists between most altitudes and the pattern of contamination of breast milk samples. The two lowest situated areas, Sahil at sea level and Ciftlikköy at 121 m above sea level were similar. We reduced the datasets by applying the interval analysis followed by similarity analyses. We observed that endrin (END1), mirex (MIRE), and pentachlorobenzene (PECB) reduce most severely the similarity.

Secondary sex ratio and trends in the associated gender-specific births near nuclear facilities in France and Germany: Update of birth counts.

Increases in childhood cancer near nuclear facilities in France and in Germany as well as elevated human birth sex ratios after the atmospheric atomic bomb tests and after Chernobyl motivated the inspection of the secondary sex ratio and the corresponding gender-specific birth counts in the vicinity of nuclear facilities. Focus is on which changes in the birth counts go along with significant changes in the sex ratios. Official municipality-specific annual birth counts by sex for all of France and for whole Germany are updated until 2016 and 2017, respectively. Using logistic regression, we determine significant change-points (jumps) after distinct radiological events in sex ratio time-trends in circular areas around pertinent nuclear facilities. With Poisson regression, we quantify the corresponding change-points in the trends of absolute annual birth counts for boys and girls. In the 35-km vicinity of the 'Centre de l'Aube Nuclear Disposal Facility (CSA)' in France in the year 2000, we observe a jump in the sex odds (SO) with sex odds ratio (SOR) 1.101; 95% CI: (1.033, 1.175), p-value 0.0033. This jump in the sex odds can be associated with a drop in boys of 3.44% (-4.02, 10.37), p-value 0.3561, and a drop in girls of 8.44% (1.33, 15.04), p-value 0.0208. In the highly populated area around the nuclear power plant Philippsburg in Germany from 2001 onward, we see a similar effect: SOR 1.027 (1.008, 1.046), p-value 0.0045; drop in boys 5.56% (2.24, 8.76), p-value 0.0012; drop in girls 6.92% (3.62, 10.10), p-value <0.0001. The presented findings corroborate and specify earlier observations and call for intensifying bio-physical research in exposure mechanisms and exposure pathways of natural or artificial ionizing radiation including neutron radiation and neutron activation. Reinforced biological and epidemiological research should aim at clarifying the associated genetic and carcinogenic consequences at the population level.

Basic principles of Hasse diagram technique in chemistry.

Principles of partial order applied to ranking are explained. The Hasse diagram technique (HDT) is the application of partial order theory based on a data matrix. In this paper, HDT is introduced in a stepwise procedure, and some elementary theorems are exemplified. The focus is to show how the multivariate character of a data matrix is realized by HDT and in which cases one should apply other mathematical or statistical methods. Many simple examples illustrate the basic theoretical ideas. Finally, it is shown that HDT is a useful alternative for the evaluation of antifouling agents, which was originally performed by amoeba diagrams.

Ranking of pharmaceuticals detected in the environment: aggregation and weighting procedures.

Pharmaceuticals are omnipresent in waste-water world-wide. Research has shown that many pharmaceuticals are not completely removed during wastewater treatment, and as a result, this has led to their occurrence being reported in waste water treatment plant effluents, rivers and lakes, and more rarely in groundwater and in drinking water. Hence, it is only logical that pharmaceutical residues in the environment and their potential toxic effects have been recognized as one of the emerging research areas in environmental chemistry. A lack of data, especially ecotoxicological and fate data on pharmaceuticals, is evident. The extent to which data are missing should therefore be looked upon in more detail in order to trigger further political steps in performing studies concerning the risk assessment of pharmaceuticals in the environment. In this investigation, we evaluate the data-availability of 16 pharmaceuticals in 17 Internet databases which means we examine a 16 (objects) x 17 (attributes) data-matrix. The consideration of the chosen pharmaceutical in databases is coded 0 = not available, or 1 = available. For the evaluation of the data-matrix, we apply the multi-criteria decision method named METEOR (Method of Evaluation by Order Theory). In contrast to conventional multi-criteria decision aids, like the well-known PROMETHEE, AHP, SMART, ORESTE as well as different versions of ELECTRE, we support the basic consideration of environmetrics: let first the data speak and let us then include subjective preferences in order to get a unique decision. The basis of METEOR is a data-matrix in which the objects are characterized by a set of attributes (indicators). By means of the attributes, a partial order is derived. In the subsequent steps, attributes are aggregated by a weighting procedure, allowing a high degree of involvement of experts, stakeholders and other participants. All conducted approaches show that the data-situation on the chosen test-set of 16 well-known and highly produced pharmaceuticals is far from being satisfactory. For the two well-known pharmaceuticals roxithomycin (antibiotic) and diatrizoate (contrast media), the data-situation is extremely bad, independent of how the weighting is performed. The data-availability for diatrizoate is a little better. The best data coverage is detected for the chemicals carbamazepine, diazepam, ethinyl estradiol, 5-fluorouracil, and phenazone. The issue of pharmaceuticals in the environment and the unavailability of data necessitate much closer communication between science and medical healthcare and politicians in the future.

Trends in the human sex odds at birth in Europe and the Chernobyl Nuclear Power Plant accident.

To investigate trends in the sex odds before and after the Chernobyl accident, gender-specific annual birth statistics were obtained from the Czech Republic, Denmark, Finland, Germany, Hungary, Norway, Poland, and Sweden between 1982 and 1992. For parts of Germany, annual birth statistics and fallout measurements after Chernobyl are available at the district level. Trend models allowing for discontinuities of the male birth proportions are suggested. Superimposed on a downward trend in male proportions there was a jump in 1987 with a sex odds ratio of 1.0047 (95%-confidence interval: 1.0013-1.0081, p=0.0061). A positive association of the male proportion in Germany between 1986 and 1991 with radioactive exposure at the district level is reflected by a sex odds ratio of 1.0145 per mSv/a (1.0021-1.0271, p=0.0218). These findings suggest a possible long-term chronic influence of the Chernobyl Nuclear Power Plant accident on the human sex odds at birth in several European countries.

Postoperative analgesia after major spine surgery: patient-controlled epidural analgesia versus patient-controlled intravenous analgesia.

BACKGROUND: Spinal fusion surgery causes severe postoperative pain, hampering reconvalescense. We investigated the efficacy of patient-controlled epidural analgesia (PCEA) in a prospective, double-blind, randomized, controlled comparison with patient-controlled IV analgesia (PCIA). METHODS: After lumbar anterior-posterior fusion receiving an epidural catheter intraoperatively, 72 patients were given either PCEA (ropivacaine 0.125% and sufentanil 1.0 microg/mL at 14 mL/h; bolus: 5 mL; lockout time: 15 min) and IV placebo or PCIA (morphine 2.0 mg/mL; bolus: 3 mg; lockout time: 15 min) and epidural placebo. Pain levels (visual analog scale 0-10), functional capabilities (turning in bed, standing, and walking), analgesic consumption, and side effects were evaluated until 72 h after surgery. RESULTS: Fourteen patients were excluded by predetermined criteria, leaving 58 patients for data analysis. Pain levels at rest and during mobilization were significantly lower in the PCEA when compared with that in the PCIA group throughout the study period (P < 0.0001 in all cases). Time until able to turn in bed was achieved earlier in the PCEA group (P < 0.05). Patients in the PCEA group were significantly more satisfied with pain therapy (P < 0.01). CONCLUSION: We conclude that PCEA with ropivacaine and sufentanil, using intraoperatively placed epidural catheters, provides superior analgesia and higher patient satisfaction when compared with PCIA after spinal fusion surgery.

Human sex ratio at birth and residential proximity to nuclear facilities in France.

The possible detrimental genetic impact on humans living in the vicinity of nuclear facilities has been previously studied. We found evidence for an increase in the human secondary sex ratio (sex odds) within distances of up to 35km from nuclear facilities in Germany and Switzerland. Here, we extend our pilot investigations using new comprehensive data from France. The French data (1968-2011) account for 36,565 municipalities with 16,968,701 male and 16,145,925 female births. The overall sex ratio was 1.0510. Using linear and nonlinear logistic regression models with dummy variables coding for appropriately grouped municipalities, operation time periods, and corresponding spatiotemporal interactions, we consider the association between annual municipality-level birth sex ratios and minimum distances of municipalities from nuclear facilities. Within 35km from 28 nuclear sites in France, the sex ratio is increased relative to the rest of France with a sex odds ratio (SOR) of 1.0028, (95% CI: 1.0007, 1.0049). The detected association between municipalities' minimum distances from nuclear facilities and the sex ratio in France corroborates our findings for Germany and Switzerland.

Ionizing radiation and the human gender proportion at birth--A concise review of the literature and complementary analyses of historical and recent data.

It has long been known that ionizing radiation causes genetic mutations and that nuclear bomb testing, nuclear accidents, and the regular and incidental emissions of nuclear facilities enhance environmental radioactivity. For this reason, the carcinogenic and genetic impact of ionizing radiation has been an escalating issue for environmental health and human health studies in the past decades. The Windscale fire (1957) and the Chernobyl accident (1986) caused alterations to the human birth sex ratio at national levels across Europe, and childhood cancer and childhood leukemia are consistently elevated near nuclear power plants. These findings are generalized and corroborated by the observation of increased sex ratios near nuclear facilities in Austria, France, Germany, Luxembourg, Switzerland, and The Netherlands. We present a concise review of the pertinent literature and we complement our review by spatiotemporal analyses of historical and most recent data. Evidence of genetic damage by elevated environmental radioactivity is provided.

Discrete mathematical data analysis approach: a valuable assessment method for sustainable chemistry.

Sustainable/Green Chemistry is a chemical philosophy encouraging the design of products and processes that reduce or eliminate the use and generation of hazardous substances. In this respect, metrical scientific disciplines like Chemometrics are important, because they indicate criteria for chemicals being hazardous or not. We demonstrated that sustainable principles in the disciplines Green Chemistry, Green Engineering, and Sustainability in Information Technology have main aspects in common. The use of non-hazardous chemicals or the more efficient use of chemical substances is one of these aspects. We take a closer look on the topic of the hazards of chemical substances. Our research focuses on data analyses concerning environmental chemicals named Persistent Organic Pollutants (POPs), which are found all over the world and pose a large risk to environment as well as to humans. The evaluation of the data is a major step in the elucidation of the danger of these chemicals. The data analysis method demonstrated here, is based on the theory of partially ordered sets and provides a generalized ranking. In our approach we investigate data sets of breast milk samples of women in Denmark, Finland, and Turkey which contained measurable levels of 20 POPs. The goal is twofold: On the one side the hazardous chemicals are to be identified and on the other side possible differences among the three nations should be detected, because in that case possible different uptake mechanisms may be supposed. The data analysis is performed by the free available software package PyHasse, written by the third author. We conclude that the data analysis method can well be applied for distinguishing between more or less dangerous existing chemicals. Furthermore, it should be used in sustainable chemistry in the same manner for detecting more and less sustainable chemicals.

Response to W. Kramer: The human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities: comment (doi:10.1007/s11356-011-0644-8).

INTRODUCTION: This paper is in response to criticism of our article "The human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities" published in Environ Sci Pollut Res 18(5):697-707, 2011. METHODS: Our findings and methods concerning the disturbed human sex odds at birth have been criticized in this journal for being artifacts of data mining, that the concept of statistical significance was misunderstood, and that confounding factors have not been accounted for. Here, we show that this criticism has no basis. We applied well-established statistical methods to large official data sets, and confounding is less important at the level of secular sex odds trends in aggregated annual figures from countries or continents. RESULTS AND CONCLUSIONS: Moreover, our results are strengthened by recent findings concerning increased infant death sex odds in Germany and increased Down syndrome prevalence at birth across Europe after Chernobyl. Prompted by our studies, an official investigation in Lower Saxony, Germany, by the "Niedersächsisches Landesgesundheitsamt (NLGA)" confirmed our observation of severely escalated sex odds within 40 km distance from the nuclear storage site in Gorleben, Germany.

The human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities.

BACKGROUND, AIM, AND SCOPE: Ever since the discovery of the mutagenic properties of ionizing radiation, the possibility of birth sex odds shifts in exposed human populations was considered in the scientific community. Positive evidence, however weak, was obtained after the atomic bombing of Japan. We previously investigated trends in the sex odds before and after the Chernobyl Nuclear Power Plant accident. In a pilot study, combined data from the Czech Republic, Denmark, Finland, Germany, Hungary, Norway, Poland, and Sweden between 1982 and 1992 showed a downward trend in the sex odds and a significant jump in 1987, the year immediately after Chernobyl. Moreover, a significant positive association of the sex odds between 1986 and 1991 with Chernobyl fallout at the district level in Germany was observed. Both of these findings, temporality (effect after exposure) and dose response association, yield evidence of causality. The primary aim of this study was to investigate longer time periods (1950-2007) in all of Europe and in the USA with emphasis on the global atmospheric atomic bomb test fallout and on the Chernobyl accident. To obtain further evidence, we also analyze sex odds data near nuclear facilities in Germany and Switzerland. DATA AND STATISTICAL METHODS: National gender-specific annual live births data for 39 European countries from 1975 to 2007 were compiled using the pertinent internet data bases provided by the World Health Organization, United Nations, Council of Europe, and EUROSTAT. For a synoptic re-analysis of the period 1950 to 1990, published data from the USA and from a predominantly western and less Chernobyl-exposed part of Europe were studied additionally. To assess spatial, temporal, as well as spatial-temporal trends in the sex odds and to investigate possible changes in those trends after the atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities, we applied ordinary linear logistic regression. Region-specific and eventually changing spatial-temporal trends were analyzed using dummy variables coding for continents, countries, districts, municipalities, time periods, and appropriate spatial-temporal interactions. RESULTS: The predominantly western European sex odds trend together with the US sex odds trend (1950-1990 each) show a similar behavior. Both trends are consistent with a uniform reduction from 1950 to 1964, an increase from 1964 to 1975 that may be associated with delayed global atomic bomb test fallout released prior to the Partial Test Ban Treaty in 1963 and again a more or less constant decrease from 1975 to 1990. In practically all of Europe, including eastern European countries, from 1975 to 1986, and in the USA from 1975 to 2002, there were highly significant uniform downward trends in the sex odds with a reduction of 0.22% to 0.25% per 10 years. In contrast to the USA, in Europe there was a highly significant jump of the sex odds of 0.20% in the year 1987 following Chernobyl. From 1987 to 2000, the European sex odds trend reversed its sign and went upward, highly significantly so, with 0.42% per 10 years relative to the downward trend before Chernobyl. The global secular trend analyses are corroborated by the analysis of spatial-temporal sex odds trends near nuclear facilities (NF) in Germany and Switzerland. Within 35 km distance from those NF, the sex odds increase significantly in the range of 0.30% to 0.40% during NF operating time. CONCLUSIONS: The atmospheric atomic bomb test fallout affected the human sex odds at birth overall, and the Chernobyl fallout had a similar impact in Europe and parts of Asia. The birth sex odds near nuclear facilities are also distorted. The persistently disturbed secular human sex odds trends allow the estimation of the global deficit of births in the range of several millions.

Influence of altitude concerning the contamination of humus soils in the German Alps: a data evaluation approach using PyHasse.

BACKGROUND, AIM AND SCOPE: In an international project named MONARPOP (Monitoring Network in the Alpine Region for Persistent and other Organic Pollutants), selected chemicals in different environmental media were analysed in the years 2004 and 2005. Seventeen pesticides were chosen and analysed in humus and mineral soil in the German Alps. The samples were taken at different altitudes. MATERIALS AND METHODS: In such a rather complex environmental datasets, it is often necessary to compare different sets of criteria and their influence on rankings. In the similarity analysis which is part of the theory of the Hasse diagram technique, we intend to calculate the similarity of different rankings. Furthermore, we perform a so-called dominance-dominance/dominance-separability method, followed by a sensitivity analysis, both subroutines in the newly developed PyHasse programme in order to find out if the concentration of the chemicals can be related to the altitudes at which the samples were taken. RESULTS AND DISCUSSION: It can be demonstrated that the altitude has a considerable influence on the concentration of some organic chemicals in humus: The concentrations of some chemicals increase with the altitude. This increase shows certain irregularities for which several explication attempts including possible effects of atmospheric stratification phenomena in valleys have been made. CONCLUSION: These results should be complemented in further studies with MONARPOP monitoring data from other Alpine countries, e.g. Austria, Switzerland, Italy and Slovenia.