Towards an operational use of benthic foraminifera for organic pollution monitoring in open and enclosed marine environments: case histories from the outer shelf off Congo and the Firth of Clyde in Scotland.

Foraminifera are among the most abundant protists in marine benthic environments. Because of their short life cycles, high biodiversity and specific ecological requirements of individual species, foraminifera react quickly to environmental disturbance, and can be successfully employed as bio-indicators of environmental change, such as those brought about by anthropogenic pollution. In the last decennia, foraminifera have been increasingly used to monitor pollution in a wide range of marine environments, such as intertidal mudflats impacted by oil spillages, harbours affected by heavy metal pollution, or eutrophicated continental shelves. Our best examples of anthropogenic eutrophication are 1) a drill cutting disposal sites at the outer continental shelf off Congo, where we observed a zonation of foraminiferal faunas in the 750 m around the discharge point. In the immediate vicinity of the discharge points (within 70 m), faunas are characterised by low foraminiferal densities. Faunas between 70 m and 250 m of the disposal sites have very high foraminiferal densities, with high percentages of opportunistic taxa such as B. aculeata and B. marginata. Between 250 and 750 m, foraminiferal densities decrease, and the percentages of opportunistic species are lower; 2) a sewage sludge disposal on the sea floor in the Firth of Clyde (Scotland) where we used benthic foraminifera and macrofaunal/meiofaunal assemblages to evaluate the impact. These two communities present a very similar distributional pattern around the disposal site. In its immediate vicinity, both groups show impoverished faunas composed exclusively of species tolerant to strong oxygen depletion. This area is surrounded by an aureole of high density faunas dominated by opportunistic species. Still farther away, faunal density decreases, and equilibrium taxa gradually replace opportunistic species. At about 3 Km of the disposal site, both foraminiferal and macro-/meiofaunal taxa become comparable to those found at the reference station. We used these data to develop a quantitative pollution index, values of which are strongly correlated with the distance to the disposal site. This foraminiferal index offers the possibility to quantify the impact of anthropogenic eutrophication in marine environments, but its validity must be tested in wider range of naturally and anthropogenetically impacted marine environments.Foraminifera are among the most abundant protists in marine benthic environments. Because of their short life cycles, high biodiversity and specific ecological requirements of individual species, foraminifera react quickly to environmental disturbance, and can be successfully employed as bio-indicators of environmental change, such as those brought about by anthropogenic pollution. In the last decennia, foraminifera have been increasingly used to monitor pollution in a wide range of marine environments, such as intertidal mudflats impacted by oil spillages, harbours affected by heavy metal pollution, or eutrophicated continental shelves. Our best examples of anthropogenic eutrophication are 1) a drill cutting disposal sites at the outer continental shelf off Congo, where we observed a zonation of foraminiferal faunas in the 750 m around the discharge point. In the immediate vicinity of the discharge points (within 70 m), faunas are characterised by low foraminiferal densities. Faunas between 70 m and 250 m of the disposal sites have very high foraminiferal densities, with high percentages of opportunistic taxa such as B. aculeata and B. marginata. Between 250 and 750 m, foraminiferal densities decrease, and the percentages of opportunistic species are lower; 2) a sewage sludge disposal on the sea floor in the Firth of Clyde (Scotland) where we used benthic foraminifera and macrofaunal/meiofaunal assemblages to evaluate the impact. These two communities present a very similar distributional pattern around the disposal site. In its immediate vicinity, both groups show impoverished faunas composed exclusively of species tolerant to strong oxygen depletion. This area is surrounded by an aureole of high density faunas dominated by opportunistic species. Still farther away, faunal density decreases, and equilibrium taxa gradually replace opportunistic species. At about 3 Km of the disposal site, both foraminiferal and macro-/meiofaunal taxa become comparable to those found at the reference station. We used these data to develop a quantitative pollution index, values of which are strongly correlated with the distance to the disposal site. This foraminiferal index offers the possibility to quantify the impact of anthropogenic eutrophication in marine environments, but its validity must be tested in wider range of naturally and anthropogenetically impacted marine environments

Benthic foraminifera as bio-indicators of eutrophicated environments

Foraminifera are among the most abundant protists in marine benthic environments (Murray, 1991). Because of their short life cycles, high biodiversity and specific ecological requirements of individual species, foraminifera react quickly to environmental disturbance, and can be successfully employed as bio-indicators of environmental change, such as those brought about by anthropogenic pollution (as defined by Kramer and Botterweg, 1991). Foraminiferal assemblages are easy to collect; foraminifera are commonly abundant, providing a highly reliable database for statistical analysis, even when only small sample volumes are available. Furthermore, many foraminiferal taxa secrete a carbonate shell, and leave an excellent fossil record, that may be used to characterise baseline conditions, and to reconstruct the state of the ecosystem prior to sampling. Studies of the effects of pollution on benthic foraminiferal assemblages, and their possible use as pollution indicators were initiated in the early 1960’s by Resig (1960) and Watkins (1961). In the last decennia, foraminifera have been increasingly used to monitor pollution in a wide range of marine environments, such as intertidal mudflats impacted by oil spillages (Morvan et al., 2004), harbours affected by heavy metal pollution (Armynot Du Châtelet et al., 2004), or eutrophicated continental shelves (Sharifi et al., 1991; Yanko and Flexer, 1991). The goal of our study is to compare different types of eutrophicated environments, under anthropogenic or natural conditions:  we used benthic foraminifera as bio-indicators of anthropogenic eutrophication caused by drill cutting discharges (Congo and Gabon), by sewage sludge (Firth of Clyde; Scotland) and by fish farms (Loch Etive; Scotland) and compared the faunal patterns with those observed in the Rhone prodelta, en environment characterised by strong natural eutrophication due to  important continental nutrient input

Oxygen impurities in NiAl: Relaxation effects

We have used a full-potential linear muffin-tin orbital method to calculate the effects of oxygen impurities on the electronic structure of NiAl. Using the supercell method with a 16-atom supercell we have investigated the cases where an oxygen atom is substitutionally placed at either a nickel or an aluminum site. Full relaxation of the atoms within the supercell was allowed. We found that oxygen prefers to occupy a nickel site over an aluminum site with a site selection energy of 138 mRy (21,370 K). An oxygen atom placed at an aluminum site is found to cause a substantial relaxation of its nickel neighbors away from it. In contrast, this steric repulsion is hardly present when the oxygen atom occupies the nickel site and is surrounded by aluminum neighbors. We comment on the possible relation of this effect to the pesting degradation phenomenon (essentially spontaneous disintegration in air) in nickel aluminides.Comment: To appear in Phys. Rev. B (Aug. 15, 2001

The Pandora's Box of Evidence Synthesis and the case for a living Evidence Synthesis Taxonomy.

Have we, as an evidence-based health community, opened the Pandora's box of evidence synthesis? There now exists a plethora of overlapping evidence synthesis approaches and duplicate, redundant and poor-quality reviews.1-4 After years of advocating for the need for systematic reviews of the evidence, there is a risk that this message been disseminated too widely and has been misinterpreted in this process. We have reached a point where in some fields more reviews exist than clinical trials, where same topic reviews are being conducted in parallel, and evidence syntheses possess limited utility for decision-making because of their poor quality or poor reporting.To paraphrase the late Douglas Altman,5 it is possible we are now at a stage where we need less reviews, better reviews and reviews done for the right reason - as opposed to the current state of mass production (approximately 80 reviews per day)6.Zachary Munn, Danielle Pollock, Timothy Hugh Barker, Jennifer Stone, Cindy Stern, Edoardo Aromataris, Holger J Schünemann, Barbara Clyne, Hanan Khalil, Reem A Mustafa, Christina Godfrey, Andrew Booth, Andrea C Tricco, Alan Pearso

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium

Aims/hypothesis The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT. Methods Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size similar to 1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires. Conclusinos/interpretation DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes

Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI Direct study

Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n=403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n=458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariate regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred was associated with healthier diets high in wholegrain (β=0.004 g, p=0.02 and β=0.003 g, p=0.03) and lower energy intake (β=-0.0002 kcal, p=0.04 and β=-0.0002 kcal, p=0.003), and saturated fat (β=-0.03 g, p<.0001 and β=-0.03 g, p<.0001), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and improved lipid profiles HDL-cholesterol (β=0.07 mmol/L, p<.0001), (β=0.08 mmol/L, p=0.0002), and triglycerides (β=-0.1 mmol/L, p=0.003), (β=-0.2 mmol/L, p=0.0002), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat content (β=-0.74 %, p<.0001), and lower fasting concentrations of HbA1c (β=-0.9mmol/mol, p=0.02), glucose (β=-0.2 mmol/L, p=0.01) and insulin (β=-11.0 pmol/mol, p=0.01). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, p=0.03) and insulin (β=-9.2 pmol/mol, p=0.04) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

The presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments

Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: an IMI-DIRECT study

Aim To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration.Methods We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI-DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven-point oral glucose tolerance test at baseline and follow-up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months.Results At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1-4. Participants in Subgroups 2-4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (beta = 0.36, 95% CI 0.13-0.58), Subgroup 3 (beta = 0.30; 95% CI 0.10-0.50) and Subgroup 2 (beta = 0.18; 95% CI 0.04-0.32), compared to Subgroup 1. The same was observed for C-peptide and insulin. Five subgroups were identified at follow-up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months.Conclusions Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified.Molecular Epidemiolog

The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

AIMS/HYPOTHESIS: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). METHODS: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. RESULTS: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. CONCLUSIONS/INTERPRETATION: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.S.Bra. was funded by the UK Medical Research Council [MC_UU_12015/3]