Sediment Toxicity Testing for Prospective Risk Assessment—A New Framework and How to Establish It

There is a recognized need to design a new framework for sediment toxicity testing that meets current scientific standards and regulatory requirements, such as reliable assessment of toxicity, which prevents any harmful effects on biodiversity, a strong capability to predict population- and community-level effects, and applicability of the results to decision-making. We propose a new framework for prospective sediment toxicity testing, and suggest solutions to the key methodological challenges that hinder establishment of this framework (comparison of sensitivities, design of test batteries, consideration of different exposure routes, extrapolations to population and community levels, use of test results for decision-making). The proposed framework consists of the following three units: test-battery system, higher-tier testing systems and additional ecological modeling, and a decision support system. The key methodologies proposed to establish this framework are compound-tailored test-battery use approach, relative sensitivity distribution analysis, toxicity tests that combine bacteria and arthropods, micro- and mesocosms studies, population and community models, and model-driven decision support systems. The proposed framework, as well as the key methods mentioned above, has the potential to improve not only prospective toxicity testing for sediments, but also ecological risk assessment in general.     

The Aquatic Environment and Textile Mill Effluents — An Ecological Risk Assessment

Textile mill effluents (TMEs) are wastewater discharges from textile mills that are involved in wet processes such as scouring, neutralizing, desizing, mercerizing, carbonizing, fulling, bleaching, dyeing, printing and other wet finishing activities. TMEs are complex mixtures containing a wide variety of chemicals which have a range of pH, temperature, colour and oxygen demand characteristics. Most wet processing mills in Canada discharge to municipal wastewater collection systems where those effluents receive some form of wastewater treatment. This paper reports the results of a tiered assessment approach that was used to determine the impacts on the aquatic environment of whole effluents discharged by wet processing textile mills in Canada. A conservative assessment indicated that no substantial threat to the aquatic environment was associated with TMEs receiving secondary or tertiary treatment, on- site or at a municipal wastewater treatment plant, prior to discharge to receiving waters. In the case of TMEs receiving only primary treatment or no treatment prior to discharge, a weight-of-evidence risk assessment supported the conclusion that those effluents could produce significant environmental harm in aquatic environments.     

“Solution-Focused Risk Assessment”: A Proposal for the Fusion of Environmental Analysis and Action

For 30 years, more attention and resources have been expended on dissecting problems (risk assessment) than on evaluating actual solutions that reduce risks. The basic dogma holds that risk assessment must precede risk management. But there is an opposite and perhaps better way: the opening question should not be “How bad is the problem?” but “How good are the solutions we might apply to the problem?” Rethinking risk assessment in this context offers three classes of benefits over the status quo. First, it can help break the endless cycle of analysis: when the goal is to know enough to decide, rather than to know everything, natural stopping points emerge. Second, it can lead to more decisions that actually achieve risk reduction, rather than pronouncements about how much risk reduction would be optimal. Third, it can highlight ways to resolve multiple risks simultaneously, avoid needless and tragic risk-risk tradeoffs, and involve affected stakeholders in debating what should be done. Arguably, the longer the disembodied analysis of risk information is allowed to proceed, the more likely it is that the “problem” will be defined in a way that blunts the free-wheeling discussion of solutions, to the detriment of human health, the environment, and the economy.     

Average Information Content Maximization—A New Approach for Fingerprint Hybridization and Reduction

Fingerprints, bit representations of compound chemical structure, have been widely used in cheminformatics for many years. Although fingerprints with the highest resolution display satisfactory performance in virtual screening campaigns, the presence of a relatively high number of irrelevant bits introduces noise into data and makes their application more time-consuming. In this study, we present a new method of hybrid reduced fingerprint construction, the Average Information Content Maximization algorithm (AIC-Max algorithm), which selects the most informative bits from a collection of fingerprints. This methodology, applied to the ligands of five cognate serotonin receptors (5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT_5A, 5-HT₆), proved that 100 bits selected from four non-hashed fingerprints reflect almost all structural information required for a successful in silico discrimination test. A classification experiment indicated that a reduced representation is able to achieve even slightly better performance than the state-of-the-art 10-times-longer fingerprints and in a significantly shorter time.     

Tonsillectomy and the Risk for Deep Neck Infection—A Nationwide Cohort Study

Background

Although the tonsils contribute to first line immunity against foreign pathogens in the upper aero-digestive tract, the association of tonsillectomy with the risk of deep neck infection remains unclear. The aim of this study was to assess the incidence rate and risk of deep neck infection among patients who had undergone a tonsillectomy.

Methods

This retrospective cohort study evaluated all patients who had undergone tonsillectomy between 2001 and 2009 as identified from the Taiwan National Health Insurance Research Database. For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched controls without a history of tonsillectomy were randomly selected. Cox Proportional hazard model and propensity score model were performed to evaluate the association between tonsillectomy and deep neck infection after adjusting for demographic and clinical data.

Results

There were 34 (71.6 cases per 100,000 person-years) and 174 (36.6 cases per 100,000 person-years) patients that developed deep neck infection in the tonsillectomized and comparison cohorts, respectively. After adjusting for covariates, patients who had undergone a tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox proportional hazard model (95% confidence interval, 1.13-2.59) and propensity score model (95% confidence interval, 1.10-2.66). This association was not altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797).

Conclusions

Based on our review of a nationwide cohort study we identified that the risk of deep neck infection is significantly increased among patients who have undergone a tonsillectomy. Additional research is needed to explore the possible mechanisms behind these findings.     

Environmental Pathway and Risk Assessment Studies of the Musi River's Heavy Metal Contamination—A Case Study

The Musi River, in Hyderabad, the capital city of Andhra Pradesh state in India, is relatively dry for most of the year except for the four monsoon months when 700–800 mm of rain falls. Throughout the year, sewage, industrial, and hospital waste is released into the river. In the present work the Musi River from Amberpet Bridge to Nallacheruvu (8 km stretch) was assessed and monitored for heavy metal contamination attributable to sewage and industrial effluents. Twelve locations were assessed for Zn, Cr, Cu, Ni, Co, As, Hg, Cd, and Pb in soils, waters, forage grass, milk, and vegetables. A sequential extraction scheme revealed that high levels of Zn, Cr, and Cu were associated with labile fractions, making them more mobile and phytoavailable. Human risk was assessed in people exposed to pollution by analyzing metals concentrations in venous blood and urine. Results showed high amounts of Pb, Zn, Cr, and Ni compared to permissible limits, attributable to the consumption of contaminated food. Metals concentrations were monitored systematically to assess risks and support management decisions to help curtail the possible entry of metals into human food chains. An assessment was also made of a possible analysis of a remediation technology for lead-contaminated soils and water.     

Fractionation,Source Identification and Risk Assessments for Heavy Metals in Soils near a Small-Scale Industrial Area (Çanakkale-Turkey)

Contamination of soils by heavy metals due to urbanization increases various environmental concerns. The objective of this research was to determine the potential sources of heavy metals in agricultural soils in the vicinity of a small-scale industrial area and to assess their environmental impacts. Soil samples were obtained from 15 different locations near a small industrial area in the Çanakkale province of Turkey. Heavy metal (Cd, Co, Cu, Ni, Pb, Zn) contents of soil samples were determined with four different geochemical fractions via a sequential extraction procedure. The results revealed that pseudo-total heavy metal concentrations were ordered in decreasing order as Zn > Pb > Cu > Ni > Co > Cd. Considering the results, Cd (1.95 ± 0.12 µg/g), Pb (39.21 ± 2.14 µg/g) and Zn (64.99 ± 8.16 µg/g) values were above the normal values specified for agricultural lands. The findings obtained from sequential extraction procedure showed that Cd (78%) and Pb (65%) existed mostly in mobile phases. Such mobile phases originated mostly from anthropogenic sources. These findings were also supported by chemometric analyses. Risk assessments pointed out that while Pb and Zn have moderate risks on the environment, Cd creates high risks.     

Microcirculatory Rarefaction in South Asians — A Potential Mechanism for Increased Cardiovascular Risk and Diabetes

People of South Asian descent have an increased risk of cardiovascular disease (CVD) and diabetes, but little is known about the microcirculation in South Asian people despite evidence that this plays an important role in the aetiology of CVD. We compared the retinal microcirculation in a population-based sample of 287 middle-aged adults (144 European 143 South Asian) matched for age and sex. Retinal photographs were taken and analysed using a validated semi-automated program and microvascular measures were compared. Blood pressure, anthropometry and fasting bloods were also measured. South Asians had significantly fewer arteriolar and venular vessels and bifurcations. Arterioles and venules were longer and venules were also more tortuous in South Asians. These differences were not explained by adjustment for traditional risk factors including blood pressure, body mass index, diabetes or measures of insulin resistance. People of South Asian descent have rarefaction of the retinal microcirculation compared to age-sex matched individuals of European descent. Reduced microvascular density could contribute to the elevated risk of CVD and impaired glucose tolerance in South Asian people.     

The discharge letter and data collection — A method for avoiding duplication

It frequently happens that following a patient consultation similar data are recorded in a number of ways in a number of places. This paper describes a method which has been used in one busy clinic to capture this data only once, effecting a saving in consultant's time, avoiding delay in data capture and ensuring consistency of databases. The implementation, using a mixture of custom programs and commercial database software, is discussed. Examples of the sort of data input and user interfaces and some future directions for extension are given. Limitations of commercial packages encountered are mentioned.     

The Modes of Binding Methyl—α (and β)-D-glucopyranosides and Some of their Derivatives to Concanavalin A—A Theoretical Approach

Abstract

The probable modes of binding of Methyl—α (and β)-D-glucopyranosides and some of their derivatives to concanavalin A have been proposed from theoretical studies. Theory predicts that βMeGlcP can bind to ConA in three different modes whereas α-MeGlcP can bind only in one mode. βMeGlcP in its most favourable mode of binding differs from α-MeGlcP in its alignment in the active-site of the lectin where it binds in a flipped or inverted orientation. Methyl substitution at the C-2 atom of the α-MeGlcP does not significantly affect the possible orientations of the sugar in the active-site of the lectin. Methyl substitution at C-3 or C-4, however, affects the allowed orientations drastically leading to the poor inhibiting power of Methyl-3-O-methyl-α-D-glucopyranoside and the inactivity of Methyl-4-O-methyl-α-D-glucopyranoside. These studies suggest that the increased activity of the α-MeGlcP over β-MeGlcP may be due to the possibility of formation of better hydrogen bonds and to hydrophobic interactions rather than to steric factors as suggested by earlier workers. These models explain the available NMR and other binding studies.     

Phenylketonuria—The Guthrie Screening Test—A Method of Quantitation,Observations on Reliability and Suggestions for Improvement

The Guthrie bacterial inhibition assay method of screening neonatal infants for phenylketonuria (pku) initiated mass screening for inborn errors of metabolism. It is a simple, cheap procedure admirably suited to private local use as against private or public central use. However, using parallel fluorometric determinations as a basis for comparison, and 4 mg per 100 ml serum phenylalanine as a presumptive positive threshhold, the Guthrie test yielded 53 per cent “false negatives.” Extrapolating from a combination of our data and reported phenylalanine levels at three days of age or less in proved pku patients, it is estimated the Guthrie test might fail to detect one of 25 pku patients screened at three days of age or less. Means to diminish this risk are considered.     

The Apache Longbow–Hellfire Missile Test at Yuma Proving Ground: Introduction and Problem Formulation for a Multiple Stressor Risk Assessment

An ecological risk assessment was conducted at Yuma Proving Ground, Arizona, as a demonstration of the Military Ecological Risk Assessment Framework (MERAF). The focus of the assessment was a testing program at the Cibola Range, which involved an Apache Longbow helicopter firing Hellfire missiles at moving targets, that is, M60-A1 tanks. The problem formulation for the assessment included conceptual models for three component activities of the test, helicopter overflight, missile firing, and tracked vehicle movement, and two ecological endpoint entities, woody desert wash communities and desert mule deer (Odocoileus hemionus crooki) populations. An activity-specific risk assessment framework was available to provide guidance for assessing risks associated with aircraft overflights. Key environmental features of the assessment area include barren desert pavement and tree-lined desert washes. The primary stressors associated with helicopter overflights were sound and the view of the aircraft. The primary stressor associated with Hellfire missile firing was sound. The principal stressor associated with tracked vehicle movement was soil disturbance, and a resulting, secondary stressor was hydrological change. Water loss to desert washes and wash vegetation was expected to result from increased ponding, infiltration, and/or evaporation associated with disturbances to desert pavement. A plan for estimating integrated risks from the three military activities was included in the problem formulation.     

The z-model — A proposal for spatial and temporal modeling of visual threshold perception

By considering only the modulation transfer functions of stationary, uniformly moved, and time modulated sinusoidal gratings it is possible to derive a simple model, the z-model, for the spatio-temporal frequency behaviour of one-dimensional patterns. The transmission function of this model is a band pass function of a single coordinate z, which is a quadratic form of the spatial and temporal frequencies (rotational symmetry with respect to space and time). The model is determined by only three constants. Optionally a time phase which accounts for delay and phase distortion can be added. This model can also be derived from reaction time measurements for switched on sinusoidal gratings. With this model the response of a wide variety of spatio-temporal patterns have been calculated and compared with measured threshold data. For two-dimensional patterns orientational filtering has to be added to the model leading to a further parameter. This model predicts satisfactorily the threshold modulation for a great variety of arbitrary spatio-temporal patterns. However the absolute threshold value for aperiodic transient patterns differs slightly in direction of smaller sensitivity as compared with periodic stationary patterns. This suggests that the peak detection scheme usually used in threshold detection modeling should be replaced by an integrative mechanism.     

The NAD World: A New Systemic Regulatory Network for Metabolism and Aging—Sirt1, Systemic NAD Biosynthesis,and Their Importance

For the past several years, it has been demonstrated that the NAD-dependent protein deacetylase Sirt1 and nicotinamide phosphoribosyltransferase (Nampt)-mediated systemic NAD biosynthesis together play a critical role in the regulation of metabolism and possibly aging in mammals. Based on our recent studies on these two critical components, we have developed a hypothesis of a novel systemic regulatory network, named “NAD World”, for mammalian aging. Conceptually, in the NAD World, systemic NAD biosynthesis mediated by intra- and extracellular Nampt functions as a driver that keeps up the pace of metabolism in multiple tissues/organs, and the NAD-dependent deacetylase Sirt1 serves as a universal mediator that executes metabolic effects in a tissue-dependent manner in response to changes in systemic NAD biosynthesis. This new concept of the NAD World provides important insights into a systemic regulatory mechanism that fundamentally connects metabolism and aging and also conveys the ideas of functional hierarchy and frailty for the regulation of metabolic robustness and aging in mammals.     

CHRONIC RENAL FAILURE—Its Effect on Calcium,Phosphorus and Osseous Metabolism; A Unified Approach

The renal osteodystrophies represent the metabolic consequences of (1) vitamin D resistance, (2) secondary hyperplasia of the parathyroids, and (3) the changes in serum PO₄= and Ca++ secondary to the renal insufficiency per se.The osseous lesion in any given patient with chronic renal failure may be osteitis fibrosa, rickets (osteomalacia), calcium deficiency osteoporosis or any combination of these. The concentration of Ca++ and PO₄= in the serum is determined by the degree of renal failure and the skeletal response to parathyroid hormone.     

Incidence and Risk Factors of Childhood Pneumonia-Like Episodes in Biliran Island,Philippines—A Community-Based Study

Pneumonia is a leading cause of deaths in infants and young children in developing countries, including the Philippines. However, data at the community level remains limited. Our study aimed to estimate incidence and mortality rates and to evaluate risk factors and health-seeking behavior for childhood pneumonia. A household level interview survey was conducted in Biliran Island, the Philippines. Caregivers were interviewed using a semi-structured questionnaire to check if children had symptoms suggesting pneumonia-like episodes from June 2011 to May 2012. Of 3,327 households visited in total, 3,302 (99.2%) agreed to participate, and 5,249 children less than 5 years of age were included in the study. Incidence rates of pneumonia-like episodes, severe pneumonia-like episodes, and pneumonia-associated mortality were 105, 61, and 0.9 per 1,000 person-years, respectively. History of asthma [hazard ratio (HR): 5.85, 95% confidence interval (CI): 4.83–7.08], low socioeconomic status (SES) (HR: 1.11, 95% CI: 1.02–1.20), and long travel time to the healthcare facility estimated by cost distance analysis (HR: 1.32, 95% CI: 1.09–1.61) were significantly associated with the occurrence of pneumonia-like episodes by the Cox proportional hazards model. For severe pneumonia-like episodes, a history of asthma (HR: 8.39, 95% CI: 6.54–10.77) and low SES (HR: 1.30, 95% CI: 1.17–1.45) were significant risk factors. Children who had a long travel time to the hospital were less likely to seek hospital care (Odds ratio: 0.32, 95% CI: 0.19–0.54) when they experienced severe pneumonia-like episodes. Incidence of pediatric pneumonia-like episodes was associated with a history of asthma, SES, and the travel time to healthcare facilities. Travel time was also identified as a strong indicator for health-seeking behavior. Improved access to healthcare facilities is important for early and effective management. Further studies are warranted to understand the causal relationship between asthma and pneumonia.     

A Specific and Essential Role for Na,K-ATPase α3 in Neurons Co-expressing α1 and α3

Most neurons co-express two catalytic isoforms of Na,K-ATPase, the ubiquitous α1, and the more selectively expressed α3. Although neurological syndromes are associated with α3 mutations, the specific role of this isoform is not completely understood. Here, we used electrophysiological and Na⁺ imaging techniques to study the role of α3 in central nervous system neurons expressing both isoforms. Under basal conditions, selective inhibition of α3 using a low concentration of the cardiac glycoside, ouabain, resulted in a modest increase in intracellular Na⁺ concentration ([Na⁺]_i) accompanied by membrane potential depolarization. When neurons were challenged with a large rapid increase in [Na⁺]_i, similar to what could be expected following suprathreshold neuronal activity, selective inhibition of α3 almost completely abolished the capacity to restore [Na⁺]_i in soma and dendrite. Recordings of Na,K-ATPase specific current supported the notion that when [Na⁺]_i is elevated in the neuron, α3 is the predominant isoform responsible for rapid extrusion of Na⁺. Low concentrations of ouabain were also found to disrupt cortical network oscillations, providing further support for the importance of α3 function in the central nervous system. The α isoforms express a well conserved protein kinase A consensus site, which is structurally associated with an Na⁺ binding site. Following activation of protein kinase A, both the α3-dependent current and restoration of dendritic [Na⁺]_i were significantly attenuated, indicating that α3 is a target for phosphorylation and may participate in short term regulation of neuronal function.