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Abstract Background Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive disorder of leucine metabolism caused by mutations in MCCC1 or MCCC2 encoding the α and β subunit of MCC, respectively. The phenotype is highly variable ranging from acute neonatal onset with fatal outcome to asymptomatic adults. Methods We report clinical, biochemical, enzymatic and mutation data of 88 MCC deficient individuals, 53 identified by newborn screening, 26 diagnosed due to clinical symptoms or positive family history and 9 mothers, identified following the positive newborn screening result of their baby. Results Fifty-seven percent of patients were asymptomatic while 43% showed clinical symptoms, many of which were probably not related to MCC deficiency but due to ascertainment bias. However, 12 patients (5 of 53 identified by newborn screening) presented with acute metabolic decompensations. We identified 15 novel MCCC1 and 16 novel MCCC2 mutant alleles. Additionally, we report expression studies on 3 MCCC1 and 8 MCCC2 mutations and show an overview of all 132 MCCC1 and MCCC2 variants known to date. Conclusions Our data confirm that MCC deficiency, despite low penetrance, may lead to a severe clinical phenotype resembling classical organic acidurias. However, neither the genotype nor the biochemical phenotype is helpful in predicting the clinical course.

Abstract Background Junior physicians are sometimes sent in ambulances with critically ill patients who require urgent transfer to another hospital. Unfamiliar surroundings and personnel, time pressure, and lack of experience may imply a risk of insufficient treatment during transportation as this can cause the physician to loose the expected overview of the situation. While health care professionals are expected to follow complex algorithms when resuscitating, stress can compromise both solo-performance and teamwork. Aim To examine whether inter-hospital resuscitation improved with a structured team briefing between physician and ambulance crew in preparation for transfer vs. review of resuscitation guidelines. The effect parameters were physician team leadership (requesting help, delegating tasks), time to resuscitation key elements (chest compressions, defibrillation, ventilations, medication, or a combination of these termed "the first meaningful action"), and hands-off ratio. Methods Participants: 46 physicians graduated within 5 years. Design: A simulation intervention study with a control group and two interventions (structured team briefing or review of guidelines). Scenario: Cardiac arrest during simulated inter-hospital transfer. Results Forty-six candidates participated: 16 (control), 13 (review), and 17 (team briefing). Reviewing guidelines delayed requesting help to 162 seconds, compared to 21 seconds in control and team briefing groups (p = 0.021). Help was not requested in 15% of cases; never requesting help was associated with an increased hands-off ratio, from 39% if the driver's assistance was requested to 54% if not (p < 0.01). No statistically significant differences were found between groups regarding time to first chest compression, defibrillation, ventilation, drug administration, or the combined "time to first meaningful action". Conclusion Neither review nor team briefing improved the time to resuscitation key elements. Review led to an eight-fold increase in the delay to requesting help. The association between never requesting help and an increased hands-off ratio underpins the importance of prioritising available resources. Other medical and non-medical domains have benefited from the use of guidelines reviews and structured team briefings. Reviewing guidelines may compromise the ability to focus on aspects such as team leading and delegating tasks and warrants the need for further studies focusing on how to avoid this cognitive impairment.

Abstract Background First responders are recommended as a supplement to the Emergency Medical Services (EMS) in order to achieve early defibrillation. Practical and organisational aspects are essential when trying to implement new parts in the "Chain of Survival"; areas to address include minimizing dispatch time, ensuring efficient and quick communication, and choosing areas with appropriate driving distances. The aim of this study was to implement a system using Basic Life Support (BLS) responders equipped with an automatic external defibrillator in an area with relatively short emergency medical services' response times. Success criteria for implementation was defined as arrival of the BLS responders before the EMS, attachment (and use) of the AED, and successful defibrillation. Methods This was a prospective observational study from September 1, 2005 to December 31, 2007 (28 months) in the city of Aarhus, Denmark. The BLS responder system was implemented in an area up to three kilometres (driving distance) from the central fire station, encompassing approximately 81,500 inhabitants. The team trained on each shift and response times were reduced by choice of area and by sending the alarm directly to the fire brigade dispatcher. Results The BLS responders had 1076 patient contacts. The median response time was 3.5 minutes (25th percentile 2.75, 75th percentile 4.25). The BLS responders arrived before EMS in 789 of the 1076 patient contacts (73%). Cardiac arrest was diagnosed in 53 cases, the AED was attached in 29 cases, and a shockable rhythm was detected in nine cases. Eight were defibrillated using an AED. Seven of the eight obtained return of spontaneous circulation (ROSC). Six of the seven obtaining ROSC survived more than 30 days. Conclusion In this study, the implementation of BLS responders may have resulted in successful resuscitations. On basis of the close corporation between all participants in the chain of survival this project contributed to the first link: short response time and trained personnel to ensure early defibrillation.

Abstract Background The scientific evidence of a beneficial effect of physicians in prehospital treatment is scarce. The objective of this systematic review of controlled studies was to examine whether physicians, as opposed to paramedical personnel, increase patient survival in prehospital treatment and if so, to identify the patient groups that gain benefit. Methods A systematic review of studies published in the databases PubMed, EMBASE and Cochrane from January 1, 1990 to November 24, 2008. Controlled studies comparing patient survival with prehospital physician treatment vs. treatment by paramedical personnel in trauma patients or patients with any acute illness were included. Results We identified 1.359 studies of which 26 met our inclusion criteria. In nine of 19 studies including between 25 and 14.702 trauma patients in the intervention group, physician treatment increased survival compared to paramedical treatment. In four of five studies including between nine and 85 patients with out of hospital cardiac arrest, physician treatment increased survival. Only two studies including 211 and 2.869 patients examined unselected, broader patient groups. Overall, they demonstrated no survival difference between physician and paramedical treatment but one found increased survival with physician treatment in subgroups of patients with acute myocardial infarction and respiratory diseases. Conclusion Our systematic review revealed only few controlled studies of variable quality and strength examining survival with prehospital physician treatment. Increased survival with physician treatment was found in trauma and, based on more limited evidence, cardiac arrest. Indications of increased survival were found in respiratory diseases and acute myocardial infarction. Many conditions seen in the prehospital setting remain unexamined.

Abstract Background Retroperitoneal packing in patients with severe haemorrhage is a cornerstone of modern pelvic fracture management. However, few Danish trauma surgeons have experience with this procedure, and trauma audits show that many hesitate to perform the procedure, indicating a need for hands-on training for this simple and potentially lifesaving procedure. Materials and methods During a six-month period, trauma surgeons were taught the retroperitoneal packing procedure using human corpses at the Department of Pathology at Aarhus University Hospital. Results The course consisted of a 30 minute long single training session in retroperitoneal packing. Twenty-three sessions were held. Forty-two trauma surgeons (the entire staff at Aarhus Trauma Centre) and ten observers completed the course. Afterwards, all participants felt competent to perform the procedure. Conclusion All 42 surgeons at our local trauma organisation learned a simple lifesaving operation within a short time period. In the 12 months following the completion of the course, 11 patients were treated with packing without any hesitation and with success. Damage control surgery with packing was cost-effectively implemented at our centre with great ease and rapidity.

Background: Digital health solutions hold the potential for supporting general practitioners in decision-making, and include telemedicine systems, decision support systems, patient apps, wearables, fitness trackers, etc. AIM: This review aimed to identify digital solutions developed for, tested, or implemented in general practice to support the decisions of GPs in disease detection and management, using Denmark as an example country of a universal healthcare setting., Methods: This study was conducted as a rapid review. The primary search included a database search conducted in Embase and MEDLINE. The supplementary search was conducted in Infomedia and additionally included a snowball search in reference lists and citations of key articles identified in the database search. Titles were screened by two reviewers., Results: The review included 15 studies as key articles describing a total of 13 digital solutions for decision support in general practice in Denmark. 1.123 titles were identified through the database search and 240 titles were identified through the supplementary and snowball search., Conclusions: The review identified 13 digital solutions for decision support in general practice in a Danish healthcare setting aimed at detection and/or management of cancer, COPD, type 2 diabetes, depression, liver disease or multiple lifestyle-related diseases. Implementation aspects should be reported more transparently in future publications to enable applicability of digital solutions as decision support to aid general practitioners in disease detection and management., (© 2023. The Author(s).)

Objectives: This study aimed to examine the risk of mortality following incident and subsequent osteoporotic fractures, the effect of different fracture type combinations, and the mediating role of postfracture morbidity in a Danish population., Methods: We used the National Patient Registry to identify patients ≥60 years with incident major osteoporotic fracture of the hip, vertebrae, wrist or humerus between 2013 and 2018, and controls matched 1:10 on age and sex. Possible mediators were identified using International Classification of Diseases, 10th Revision codes registered in the 6 months following index fracture. HRs were estimated using Cox regression analyses with 95% CIs. The effect of possible mediators was estimated using mediation analyses., Results: The study included 106 303 patients and 1 062 988 controls. Mortality following index fracture was highest in the month following hip fractures (HR 10.98 (95% CI 10.23 to 11.79) in women and HR 16.40 (95% CI 15.00 to 17.93) in men). Subsequent hip fractures resulted in the highest HRs for all fracture type combinations. In women, the highest HR was observed in patients with index wrist/subsequent hip fractures (HR 2.43 (95% CI 2.12 to 2.78)). In men, the highest HR was observed in patients with index humerus/subsequent hip fractures (HR 2.69 (95% CI 2.04 to 3.54)). Pneumonia mediated the largest proportion of mortality, but dehydration, urinary tract infection and sepsis were also important factors., Conclusions: The highest mortality risk was found in the month immediately following both index and subsequent fracture. The combination of index and subsequent fractures at different skeletal sites had a substantial impact on the risk of mortality. Postfracture morbidities were found mediate the association., Competing Interests: Competing interests: ERC, AC, TGP, SM and KHR declare no competing interests. BA reports institutional research grants and personal fees from UCB, institutional research grants and personal fees from Kyowa-Kirin, institutional research grants and personal fees from Pharmacosmos, speakers fees from Amgen and speakers fees from Gedeon-Richter. MKS reports an educational grant from UCB, institutional research grants from UCB/Amgen and Region Zealand Health Scientific Research Foundation and a personal speakers fee from UCB Nordic., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

An accurate assessment of time since fracture is an essential component of abuse and death investigations; however, little evidence-based research exists on dating fractures, especially those of the cranial vault. This is primarily due to difficulties in procuring human fracture specimens of known posttraumatic survival times. The aim of this article is to introduce a new database through which limitations imposed by sample procurement may be mitigated. The Repository of Antemortem Injury Response (REPAIR) is a digitally accessible database of cranial vault fractures of known ages with extensive contextual information and visual documentation in the form of photography, radiography, and histological photomicrographs. This repository is a multifunctional tool that serves as a case submission portal for cranial fractures of known posttraumatic survival time, a sample database for research on fracture healing and rates of repair, a resource for comparative assessments of cranial fractures in forensic casework, and an educational tool for healing fracture histomorphology., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ultracold hybrid ion-atom gases represent an exciting frontier for quantum simulation offering a new set of functionalities and control. Here, we study a mobile ion immersed in a Bose-Einstein condensate and show that the long-range nature of the ion-atom interaction gives rise to an intricate interplay between few- and many-body physics. This leads to the existence of several polaronic and molecular states due to the binding of an increasing number of bosons to the ion, which is well beyond what can be described by a short-range pseudopotential. We use a complementary set of techniques including a variational ansatz and field theory to describe this rich physics and calculate the full spectral response of the ion. It follows from thermodynamic arguments that the ion-atom interaction leads to a mesoscopic dressing cloud of the polarons, and a simplified model demonstrates that the spectral weight of the molecules scale with increasing powers of the density. We finally calculate the quantum dynamics of the ion after a quench experiment.

A recent data set for 22 poly- and per-fluorinated compounds (PFASs) in Ponar grab samples of surface sediments and cores from the Great Lakes of North America was examined for concentrations, loads, correlations with geographical coordinates and depth (time), and for sources. Correlations were determined by multivariate regression analyses. Source apportionment of PFASs was carried out by positive matrix factorization (PMF) for two cores from Lake Ontario. For the five lakes together, the total load of PFASs in sediments was estimated to be 245 ± 24 tonnes, which is about half the load for total PCBs. The recent annual loading was 1812 ± 320 kg/yr. Concentrations and inventories of PFASs were greatest in Lakes Erie and Ontario. Since 1947, concentrations of perfluorooctane sulfonic acid (PFOS) in ten cores have increased exponentially as a function of time with doubling times between 10 and 54 yr and have leveled off in three cores since 2000. PMF demonstrated an effective grouping of two particle-associated factors, characterized mainly by longer-chain PFASs (C ≥ 8) and two other factors of mainly shorter-chain compounds (C ≤ 6). Two factors feature only one dominant compound: factor 1, PFOS, and factor 3, perfluorobutane sulfonic acid (PFBS). Of all factors, factor 3 with PFBS has the largest contribution (47.8%). Significant scores for perfluorohexane sulfonic acid (PFHxS) and PFBS, along with flat or decreasing PFOS contributions since 2003, indicate that the replacement of PFOS with these compounds is beginning to take effect in the environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

BACKGROUND Significant geographical disparities exist in stroke prevalence among southeastern states, including North Carolina. Additionally, stroke is more prevalent in rural areas. Peer support groups play an important role in stroke recovery by providing tools for effective coping, alleviating psychological stress, and creating an outlet for stroke survivors and caregivers. However, their perceived benefits have not been clearly defined for rural stroke survivors and their families. METHODS This qualitative study describes the experiences of survivors and caregivers in rural North Carolina who have participated in stroke peer support groups. Four focus groups were conducted with 32 participants (average age 67 years, 72% female) in 4 rural North Carolina counties, using a semi-structured discussion guide and an inductive coding approach. RESULTS Thematic analysis revealed that participants in rural support groups seek and receive knowledge from their support groups and feel empowered by providing and receiving this knowledge. Shared experiences cultivate a sense of community, and participants viewed support outside of the support group as necessary to their recovery process. LIMITATIONS This study reflects the views of a small group of predominantly non-Hispanic, white stroke survivors and caregivers who voluntarily participated. We did not conduct separate focus groups with survivors and caregivers. CONCLUSION Peer support groups are a sparse, but critical resource for rural stroke survivors and caregivers because they provide information and community that can assist with recovery to health and independence., (©2019 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ&#95;{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ&#95;{11} is determined via sub-Coulomb α-transfer reactions or the β-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the β-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b&#95;{β,11}=(5.02±0.10)×10^{-2}] and for β-delayed α emission [b&#95;{βα}=(1.59±0.06)×10^{-5}]. Our value for b&#95;{βα} is 33% larger than previously held, leading to a substantial increase in γ&#95;{11}. Our revised value for γ&#95;{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ&#95;{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

Data sets for concentrations of up to 22 elements including Pb, Cd, Ag, As, and Hg and several rare earth elements (REEs) in moss and surface soil from all over mainland Norway are analyzed by positive matrix factorization (PMF) and principal component analysis (PCA) with centered log-ratio transformation. Moss and soil samples collected in 2010 and 2005, respectively, show both a distinct long-range atmospheric transport PMF factor including a dominant Pb loading along with smaller loadings of Mo, Cd, Sb, and As, and a geogenic factor dominated by Ce, La, and Y. Other PMF factors for moss and soil are mainly anthropogenic except for two soil factors, a Cr, Co, Ce dominated factor, and an Eu factor. The source area of Eu is mainly inland consistent with its divalent oxidation state. A significant advantage of PMF factors is that their loadings are scaled according to their relative factor contributions. The PMF air pollution factor F3 in moss with average contribution of 7.11μg/g produces an air pollution input of 5.0μg/g which compares well with literature values for the total Pb concentration in moss for 2005 in southern Norway. PCA has the advantage that it can separate factors with very low element concentrations. To support sources of elements identified by PCA it is recommended to include calculation of factor scores to identify significant source areas., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A previously generated data set for polybrominated diphenyl ethers (PBDEs) in dated sediment cores of West Lake of El Dorado (AED), Calion Lake (ACL), and the lagoon of Magnolia Wastewater Treatment Facility (AMW) from Southern Arkansas is examined by a weighted chemical mass balance (CMB) model and positive matrix factorization (PMF) in order to quantify PBDE sources and debromination. DNA extraction and pyrosequencing were done on several core sections in order to investigate microbial debromination. CMB and PMF analyses indicate that deca technical mixtures are the dominant PBDE input (>99% in mole fraction in AED and ACL, and 94.7% in AMW). Minor contributions of penta and octa technical mixtures were found in all three water bodies (<1% in AED and ACL; and 1.1% and 4.1% in AMW, respectively). Results suggest that debromination takes place in all three lakes, but is more intense in AMW. In-situ microbial debromination was supported by the microorganism analysis. The PMF results are validated by PBDE manufacturing records, and the operating history of AMW. Despite the high PBDE concentrations in these sediments near former manufacturing facilities, the extent of debromination is limited, possibly due to sorption to natural organic matter of the sediment.

This work intended to explain the challenges of the fingerprints based source apportionment method for polycyclic aromatic hydrocarbons (PAH) in the aquatic environment, and to illustrate a practical and robust solution. The PAH data detected in the sediment cores from the Illinois River provide the basis of this study. Principal component analysis (PCA) separates PAH compounds into two groups reflecting their possible airborne transport patterns; but it is not able to suggest specific sources. Not all positive matrix factorization (PMF) determined sources are distinguishable due to the variability of source fingerprints. However, they constitute useful suggestions for inputs for a Bayesian chemical mass balance (CMB) analysis. The Bayesian CMB analysis takes into account the measurement errors as well as the variations of source fingerprints, and provides a credible source apportionment. Major PAH sources for Illinois River sediments are traffic (35%), coke oven (24%), coal combustion (18%), and wood combustion (14%)., (Copyright © 2015. Published by Elsevier Ltd.)

A stochastic process was developed to simulate the stepwise debromination pathways for polybrominated diphenyl ethers (PBDEs). The stochastic process uses an analogue Markov Chain Monte Carlo (AMCMC) algorithm to generate PBDE debromination profiles. The acceptance or rejection of the randomly drawn stepwise debromination reactions was determined by a maximum likelihood function. The experimental observations at certain time points were used as target profiles; therefore, the stochastic processes are capable of presenting the effects of reaction conditions on the selection of debromination pathways. The application of the model is illustrated by adopting the experimental results of decabromodiphenyl ether (BDE209) in hexane exposed to sunlight. Inferences that were not obvious from experimental data were suggested by model simulations. For example, BDE206 has much higher accumulation at the first 30 min of sunlight exposure. By contrast, model simulation suggests that, BDE206 and BDE207 had comparable yields from BDE209. The reason for the higher BDE206 level is that BDE207 has the highest depletion in producing octa products. Compared to a previous version of the stochastic model based on stochastic reaction sequences (SRS), the AMCMC approach was determined to be more efficient and robust. Due to the feature of only requiring experimental observations as input, the AMCMC model is expected to be applicable to a wide range of PBDE debromination processes, e.g. microbial, photolytic, or joint effects in natural environments., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Graphene (G) is attracting significant attention because of its unique physical and electronic properties. The production of graphene through the reduction of graphene oxide (GO) is a low-cost method. The reduction of GO can further lead to electrically conductive reduced GO. These graphene-based nanomaterials are attractive for high-performance water sensors due to their unique properties, such as high specific surface areas, high electron mobilities, and exceptionally low electronic noise. Because of potential risks to the environment and human health arising from heavy-metal pollution in water, G-/GO-based water sensors are being developed for rapid and sensitive detection of heavy-metal ions. In this review, a general introduction to graphene and GO properties, as well as their syntheses, is provided. Recent advances in optical, electrochemical, and electrical detection of heavy-metal ions using graphene or GO are then highlighted. Finally, challenges facing G/GO-based water sensor development and outlook for future research are discussed.

The objective of this work is to identify the photolytic debromination pathways of polybrominated diphenyl ethers (PBDEs). Thirteen PBDEs (BDEs 209, 208, 207, 206, 196, 183, 154, 153, 100, 99, 85, 47 and 28) in hexane were individually exposed to sunlight for up to 64 h. A total of 180 PBDEs were screened and 74 BDE debromination products were detected. The disappearance rate constant increased exponentially with increasing number of bromines. While no evident difference in debromination preference among ortho, meta and para bromines was found for heavier congeners, the vulnerability rank order was meta ≥ ortho > para for the lighter congeners (≤8 Br). The total molar mass of PBDEs continuously decreased during sunlight exposure, indicating PBDEs were transformed to non-PBDE compounds. A stochastic least squares debromination pathway model was developed to simulate the reactions and determine the yields to extend the results beyond the experimental observations., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

South-central Arkansas (AR) is home to major manufacturing facilities for brominated flame retardant chemicals (BFRs) in the U.S. Unintended release during production may have caused accumulation of the BFRs in the local environment. In this work, sediment cores were collected from six water bodies in AR, including three located close to the BFR manufacturing facilities in El Dorado and Magnolia, to investigate past and recent deposition histories. A total of 49 polybromodiphenyl ethers (PBDEs) and decabromodiphenyl ethane (DBDPE) were detected, with concentrations as high as 57000 and 2400 ng/g dry weight for decabromodiphenyl ether (BDE209) and DBDPE, respectively. Log-log regression of BDE209 and DBDPE surface concentrations versus distance to known BFR manufacturing facilities fit the Gaussian Plume Dispersion model, and showed that, if the distance is shortened by half, concentrations of BDE209 and DBDPE would increase by 5-fold. The spatial distribution and temporal trend of the contamination indicate that the manufacturing of PBDEs and DBDPE is the primary source for these compounds in the environment of southern Arkansas. Interestingly, the occurrence of debromination of PBDEs in the sediments of a previously used wastewater sludge retention pond in Magnolia is indicated by the presence of congeners that had not been detected in any commercial PBDE mixtures and by increased fractions of lower brominated congeners relative to higher brominated congeners. Two unknown brominated compounds were detected in the sediments, and identified as nonabromodiphenyl ethanes.

Anaerobic digesters provide clean, renewable energy (biogas) by converting organic waste to methane, and are a key part of China's comprehensive rural energy plan. Here, experimental and modeling results are used to quantify the net greenhouse gas (GHG) reduction from substituting a household anaerobic digester for traditional energy sources in Sichuan, China. Tunable diode laser absorption spectroscopy and radial plume mapping were used to estimate the mass flux of fugitive methane emissions from active digesters. Using household energy budgets, the net improvement in GHG emissions associated with biogas installation was estimated using global warming commitment (GWC) as a consolidated measure of the warming effects of GHG emissions from cooking. In all scenarios biogas households had lower GWC than nonbiogas households, by as much as 54%. Even biogas households with methane leakage exhibited lower GWC than nonbiogas households, by as much as 48%. Based only on the averted GHG emissions over 10 years, the monetary value of a biogas installation was conservatively estimated at US$28.30 ($16.07 ton(-1) CO(2)-eq), which is available to partly offset construction costs. The interaction of biogas installation programs with policies supporting improved stoves, renewable harvesting of biomass, and energy interventions with substantial health cobenefits are discussed.

Runoff coefficients are usually considered in isolation for each drainage area with resulting large uncertainties in the areas and coefficients. Accurate areas and coefficients are obtained here by optimizing runoff coefficients for characteristic Geographic Information Systems (GIS) subareas within each drainage area so that the resulting runoff coefficients of each drainage area are consistent with those obtained from runoff and rainfall volumes. Lack of fit can indicate that the ArcGIS information is inaccurate or more likely, that the drainage area needs adjustment. Results for 18 drainage areas in Milwaukee, WI for 2000-2004 indicate runoff coefficients ranging from 0.123 for a mostly residential area to 0.679 for a freeway-related land, with a standard error of 0.047. Optimized runoff coefficients are necessary input parameters for monitoring, and for the analysis and design of in situ stormwater unit operations and processes for the control of both urban runoff quantity and quality.

Clostridium difficile is a strict anaerobic spore-forming bacterium, and an increasingly common nosocomial pathogen. The U.S. Environmental Protection Agency (EPA) is responsible for the registration of disinfectants, including products designed to treat environmental surfaces contaminated with spores of C. difficile. Product efficacy data are required for registration; however, there is a lack of methodology for generating high-quality spore suspensions for evaluating product performance. As such, a study was carried out to select a suitable C. difficile strain and to develop a stand-alone method to prepare a spore suspension that meets specific criteria necessary for quantitative testing of disinfectants. The criteria are: (1) a spore titer of > 8 log10/mL, (2) > or = 90% spores to vegetative cells, and (3) resistance of spores (determined by viability) to 2.5 M hydrochloric acid (HCl). Several strains of C. difficile (toxigenic and nontoxigenic) were grown on various media (solid and liquid) for varying lengths of time to determine the best combination of incubation conditions and media to optimize spore production and quality. Once the spore production procedure was optimized, a toxigenic strain of C. difficile [American Type Culture Collection (ATCC) 43598] was selected for use in trials to verify repeatability from one production run to the next. The spore suspension was initiated by spreading vegetative cells of C. difficile (ATCC 43598) on CDC anaerobic 5% sheep blood agar plates and incubating for 7-10 days at 36 +/- 1 degrees C under anaerobic conditions. Spores were harvested when > or = 90% of the cells converted to spores as determined by observation using phase-contrast microscopy. The spores were washed three times with saline-Tween-80, resuspended in cold deionized water, heated to 70 degrees C for 10 min, evaluated microscopically for quality, and enumerated on cycloserine-cefoxitin-fructose agar containing horse blood and taurocholate. The spore suspension was used to inoculate brushed stainless steel carriers (1 cm in diameter) with and without a soil load in accordance with the Standard Quantitative Carrier Disk Test Method (ASTM E-2197-02) to determine carrier load. Once it was determined that > 6 log10 spores/carrier could be recovered, spores were evaluated for resistance to HCI. The sporulation method presented in this report is simple and repeatable and results in spore suspension of high titer (> 8 log10/mL) and quality (> or = 90% spores to vegetative cells) that met acid resistance criteria (spores were resistant to 2.5 M HCI for 10 min). In addition, recovery from brushed stainless steel carriers with and without soil load was > 6 log10 spores/carrier. A 6 log10 performance standard was set forth in the EPA's interim guidance for generating data to support a label claim for effectiveness against C. difficile spores on hard, nonporous surfaces. This precollaborative investigation successfully demonstrated the use of a methodology for in vitro production of C. difficile spores (ATCC 43598) necessary for conducting efficacy tests. A proposal will be submitted to the AOAC INTERNATIONAL Methods Committee on Antimicrobial Efficacy Testing for a collaborative study; see Appendix.

The gas chromatographic (GC) retention times of 180 polybrominated diphenyl ethers (PBDEs) were obtained under different operational conditions on two types of commonly used capillary columns, Restek Rtx-1614 and J&W DB-5MS, of different dimensions. The relative retention times (RRTs) for PBDEs were calculated by normalizing the retention times of individual congeners to the sum of those of BDEs 47 and 183. In clear contrast to polychlorinated biphenyls (PCBs), the elution of PBDEs has few cross-homolog overlaps, and this observation is discussed in terms of molecular conformation with regard to co-planarity. Within a homolog, ortho substitution in PBDEs tends to decrease GC retention, and such an effect is stronger for higher homologs. With the RRT database established in this work, a simple approach is evaluated for the identification of all mono to hepta PBDEs from the RRTs of 39 congeners under various GC conditions to facilitate the identification of unknown PBDE peaks for which chemical standards are not available., (Copyright 2010 Elsevier B.V. All rights reserved.)

Two easily available multivariate source apportionment models, Unmix and positive matrix factorization (PMF), often produce nearly the same source apportionment. However, this paper gives two examples in which this is not the case: a simulated air pollution data set of 8 species and 200 samples and a water quality data set of 32 PCB congeners and 106 sediment core samples from Sheboygan River Inner Harbor, WI. In the first case, a basic form of PMF fails primarily because the source compositions do not have any species with zero or near zero concentrations. Unmix produces source compositions and contributions that are much closer to the true values. A version of PMF with an adjustable parameter also gives good results. In the second case, each model found 5 sources for the Sheboygan PCB sediment data. PMF determined sources compositions were consistent with the original 50/50% Aroclor 1248/1254 mixture, a previously determined prominent dechlorination profile (processes H' + M), and three other partially dechlorinated profiles. The Unmix determined source compositions were not as successful as the Unmix results depended heavily on just three data points. Source apportionment results favor Unmix when edges in the data are well-defined and PMF when several zeros are present in the loading and score matrices. Since both models are seen to have potential weaknesses, both should be applied in all cases. If the two methods do not produce similar results the methods given in the paper can be used to select the model result most likely to be closest to the truth.

We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose-response models on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4-4-(trifluoromethyl)phenoxy-phenol) with ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357 mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using probit or Weibull models are calculated by nonlinear regression on the whole dataset using a dose-response regression program with variance weighting and proper inverse estimation. The Weibull model provides the best fit to the data for all four chemicals. Predicted EC10s (95% confidence limits) from our derived equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy-phenol and the probit model, we obtain 1.40 (1.22-1.61) mg/L versus 1.40 (1.20- 1.64) mg/L obtained from the nonlinear regression program. The main advantage of the approach is that EC10 or ECx (where x = 1-99) can be predicted from well-determined responses around EC20 to EC80 without experimental data in the low- or high-response range. Problems with the estimation of confidence interval for EClow,x (concentration predicted to cause x% inhibition) from algal growth inhibition also are addressed. Large confidence intervals may be the result of experimental error and lack of a well-defined reference response value.

A washoff rate equation for stormwater pollutants is presented based on linear buildup of pollutant mass in the watershed. The expression was applied to residential and open land areas that have not previously been considered even though these areas are major sources of metals, nutrients, and bacteria in stormwater runoff. The transport coefficient c was determined from the nearly constant portion of the hydrograph at the peak of each runoff event. Values of c (cm(-1)) for seven metals, i.e., Zn, Cu, Cd, Ni, Pb, Hg, and Ag (3.03+/-1.34-6.10+/-2.55 cm(-1)), TSS, BOD(5), total phosphorus (TP), E. coli, and fecal coliform (2.12+/-0.907-7.16+/-2.72 cm(-1)) were estimated using this equation. The washoff rate was developed to reflect mixed land uses based on mass deposition and effective area. The order of transport coefficients for metals is Pb>Ag>Zn>Cu>Ni>Hg>Cd reflecting decreasing particle association. For all parameters this order is TSS>fecal coliform>E. coli>Pb>BOD(5) BOD(5)>Ag>Zn>Cu>Ni>Hg>Cd>TP. The washoff rate and a related pollutant concentration model are expected to be useful for the development of best management practices for stormwater.

To reduce the combined sewer overflows (CSOs) and improve surface water quality in the Greater Milwaukee area, construction of a 19.5-mile (31.4 km) inline storage system (ISS) was completed in 1994 to capture and convey sanitary sewage and stormwater for treatment. However, one to six overflows per year still occur. Chemical mass balance (CMB) and positive matrix factorization (PMF) modeling was done in order to find origins of flows and pollutants in CSOs. Based on overflow events from 2000 to 2006 (CMB) and 2004 to 2006 (PMF), we found that between 27% and 56% of the total overflow is from sanitary sewage and most of the remaining from stormwater with possible minor contribution (< or = 8%) from groundwater. Most total suspended solids and metals (Cd, Cr, Cu, Pb, Ni, Hg, and Zn) are from stormwater, while sanitary sewage carries large contributions (> or = 28%) of BOD5, NH3, and total phosphorus. The fraction of NH3 is especially high, i.e., > or = 58%. Implications for a possible future sewer separation in combined sewer areas into separate sanitary and storm sewers are discussed.

A load model for stormwater constituents is proposed that describes mass retained on the drainage area after previous storms, as a function of a weighted sum of previous antecedent dry periods. It was used to compute the event load for 14 constituents--zinc, copper, cadmium, nickel, chromium, lead, mercury, silver, total suspended solids (TSS), E. coli, fecal coliform, total soluble phosphorus, total phosphorus, and 5-day biochemical oxygen demand. The results show acceptable fits for most constituents based on over 400 rain events (2000 to 2004) in Milwaukee, Wisconsin. Considering the retained pollutant mass after one previous storm rather than assuming the area to be clean after the previous storm gives more accurate results for all constituents, except TSS and silver. The model can be used for mixed land-use areas. The ratios of deposition fluxes of zinc and individual metals were determined at a major parking lot producing a profile characteristic of automobile emissions.

The Lomb periodogram and discrete Fourier transform are described and applied to harmonic analysis of two typical data sets, one air quality time series and one water quality time series. The air quality data is a 13 year series of 24 hour average particulate elemental carbon data from the IMPROVE station in Washington, D.C. The water quality data are from the stormwater monitoring network in Milwaukee, WI and cover almost 2 years of precipitation events. These data have irregular sampling periods and missing data that preclude the straightforward application of the fast Fourier transform (FFT). In both cases, an anthropogenic periodicity is identified; a 7-day weekday/ weekend effect in the Washington elemental carbon series and a 1 month cycle in several constituents of stormwater. Practical aspects of application of the Lomb periodogram are discussed, particularly quantifying the effects of random noise. The proper application of the FFT to data that are irregularly spaced with missing values is demonstrated on the air quality data. Recommendations are given when to use the Lomb periodogram and when to use the FFT.

Apportionment of sources of polycyclic aromatic hydrocarbons (PAHs) by a factor analysis model based on time records for seven sediment cores from central Lake Michigan is reconsidered to provide a more quantitative treatment, and one additional factor (source). The effect of mixing depth was observed on the unmixed fluxes, and a computer program was developed for estimation of the average PAH fluxes from the reconstructed PAH records. The new factor analysis model with nonnegative constraints includes not only scaling but also back scaling which improved the source apportionment significantly. One core, CLM-A, was an outlier and was omitted from the analysis. Wood burning was identified as a third major source of PAHs in the area (20% of the total PAH flux). The other two sources petroleum (traffic), 45%, and coal (coke oven emissions), 35%, became more apparent, where the contributions are based on the sum of concentrations of 16 PAH compounds. A reduced mixing depth (1.0-1.5cm) was found to be more appropriate than the originally estimated mixing depth (1.5-2.0cm).

Nine sediment cores were collected from the Sheboygan River Inner Harbor, WI, and analyzed for polychlorinated biphenyl (PCB) congeners. Total PCBs ranged from approximately 0 to 161 mg/g. Positive matrix factorization (PMF) was applied to the PCB data setto determine source profiles. Two factors were determined to be significant. One factor resembled the original approximated PCB mixture of 50% Aroclor 1248 and 50% Aroclor 1254 and the other factor was a dechlorinated version of the mixture. An anaerobic dechlorination model was applied to the dechlorinated source profiles to quantify possible dechlorination pathways. It was found that dechlorination process H' provided the best fit for an individual process, and H' + M provides the best fit for combined processes. PMF source contributions, and plots of PCB concentration versus congener for individual samples, provide evidence of enhanced dechlorination at high concentrations (>40 ppm) and small amounts of dechlorination at low concentrations (<3 ppm). In addition, downward migration of lower chlorinated PCBs in core SR1a has occurred. Remediation dredging in the Upper Sheboygan River in 1989 and 1990 reintroduced PCBs to the water column and selective transport of PCB 18 is observed in core SR7.

Four sediment cores were collected from Lake Hartwell, SC, in 1987 and 1998 and analyzed for polychlorinated biphenyl (PCB) congeners. Total PCBs ranged from -0 to 58 microg/ g. Positive matrix factorization (PMF) was applied to the data sets to determine PCB source profiles. Two factors were determined for each data set. One factor resembled the original estimated PCB mixture of 80% Aroclor 1016 and 20% Aroclor 1254 and the other factor was a dechlorinated version of the mixture. Evidence of a dechlorination plateau is apparent from the PMF loading solutions because the dechlorinated congener profiles do not change from 1987 to 1998, butthe contribution to the profile from the dechlorinated factor increases from 73% (1987) to 87% (1998). PMF source contributions and plots of PCB concentration versus congener for individual samples provide evidence of enhanced dechlorination at high concentrations. After source apportionment an anaerobic dechlorination model was applied to the dechlorinated source profiles to quantify possible dechlorination pathways. It was found that dechlorination process M, extended to target biphenyl rings with up to six chlorines, provided the best fit for an individual process, and M + Q provides the best fit for combined processes, although M + LP also provides a similarfit. Process LP targets the higher chlorinated congeners and appears to dechlorinate PCBs in the sediments initially.

A closed-system algal toxicity test with no headspace was applied to evaluate the toxicity of 11 aldehydes and two nitriles to Raphidocelis subcapitata. Algal growth rate and dissolved oxygen (DO) production were used as the test endpoints. Compared to literature data, our test results based on the endpoint of DO production is 2.5 to 257 times more sensitive than the conventional algal batch tests. In addition, our analyses show that different relative toxicity relationships may be observed when different test methods or different endpoints are applied. The test alga was found to be quite sensitive to aldehydes, and a quantitative structure-activity relationship (QSAR) relationship was established based on the n-octanol/water partition coefficient (log Kow). This study also evaluated the combined effects of aldehydes and nitriles. Four synergistic joint actions related to malononitrile were identified. On the other hand, most of the combined effects between aldehydes and acetonitrile were antagonistic. In general, we find that greater-than-additive effects mainly are associated with toxicants displaying flat dose-response curves, and less-than-additive effects may be related to certain steep-slope chemicals. Model analyses show that the above mixture toxicity behavior may be due to response addition or response multiplication joint action modes.

Sources of polycyclic aromatic hydrocarbons (PAHs) in the Black River and Ashtabula River sediments were apportioned using a factor analysis (FA) model with nonnegative constraints. Source profiles, contributions (microg/g) and percent contributions are determined with no prior knowledge of sources. The FA model includes scaling and backscaling of data with average PAH concentrations, without sample normalization. The present work is a follow-up to studies that used a chemical mass balance model to apportion sources to the same data sets. Literature source profiles, modified based on gas/particle partitioning of individual PAHs, from nine PAH sources were considered for comparison. FA results for a three-source solution indicate traffic (58%), coke oven (26%), and wood burning/coal tar (16%) are the primary PAH sources to Black River sediments. The primary PAH sources to the Ashtabula River sediments are traffic (51%), coke oven (44%), and wood burning (5%). This work supports the previous studies of Black River and Ashtabula River PAHs by CMB model. In addition, FA provides a more realistic fit to Ashtabula River model data by eliminating 100% contributions from one source.

Polychlorinated biphenyl (PCB) congeners were analyzed in eight deep, dated sediment cores collected from the immediate upstream and downstream of DePere dam in Fox River, Wisconsin. The average time span of the cores is about 100 yr, except for one core (FR-9) which is influenced by mixing or covers a short time period (2 yr). The total PCB concentrations have a range of 0.2-6.8 ppm for the upstream and 0.3-17.6 ppm for the downstream cores. The PCB data obtained from the sampling were analyzed as upstream and downstream data, using a factor analysis (FA) model with nonnegative constraints to identify PCB sources and congener patterns. The factor loadings obtained from the FA model were interpreted in terms of the presence of possible environmental degradation mechanisms. In addition, a recently developed model, which is used to identify and quantify possible pathways of anaerobic dechlorination of PCBs in the sediments, was validated on the basis of in situ data from the literature, and then applied to the congener patterns obtained from the FA model. The major PCB source to the Fox River sediments is identified as Aroclor 1242, for both the upstream and the downstream sediments. Loss of di- and trichlorobiphenyls (e.g., 2-4, 25-2) from the sediments suggests desorption from the sediments. On the other hand, observation of elevated amounts of certain congeners such as 24-3 and 25-3 indicates the presence of anaerobic dechlorination activity. The anaerobic dechlorination model demonstrates significant similarities between the Aroclor 1242 profile altered according to dechlorination processes Q (upstream) and H' (downstream) and the dominant congener patterns obtained from the FA model.

A factor analysis model with nonnegative constraints (FA) was used to apportion the sources of PAHs found in sediments of Lake Calumet and surrounding wetlands in southeast Chicago. Source profiles and contributions, with uncertainties, are determined with no prior knowledge of sources. The model includes scaling and backscaling of data with average PAH concentrations without sample normalization. This work is a follow-up to a study that used a chemical mass balance (CMB8.2) model to apportion sources to the same data set. Literature source profiles, modified based on gas/particle partitioning of individual PAHs, from eight PAH sources were considered for comparison. FA results for a two-source solution indicate coke oven (45%) and traffic (55%) are the primary PAH sources to Lake Calumet sediments. A six-source FA solution indicates that coke oven (47%) and traffic (45%) related sources are major PAH sources and wood burning-coal residential (2.3%) is a minor PAH source. From the six-source solution, two coke oven profiles are observed, a standard coke oven profile (33%), and a degraded or second coke oven profile (14%) low in phenanthrene and pyrene. Observed traffic related sources include gasoline engine (36%) exhaust and traffic tunnel air (9.3%). This work supports the previous study of Lake Calumet PAHs by CMB model. In addition, FA provides new insights since wood burning and secondary coke oven profiles were not recognized in the CMB model.

The toxicity of two amines, nonylamine and decylamine, which have a narcotic effect on organisms, and ethylparathion (enzymatic inhibitor) on Daphnia magna has been studied when acting singly and in joint toxicity tests. This was done on the basis of an isobologram method where curves of constant response, i.e., isoboles are plotted vs. the concentrations of the two toxicants. The concentrations that immobilized 50, 10, and 0% of the test population in 48 h (IC50-48h, IC10-48h, and IC0-48h) were calculated. It is shown that nonylamine-decylamine mixtures follow a near concentration addition model of joint toxicity, while ethylparathion-decylamine mixtures follow a less than additive or near independent action model. The study was performed using three toxicity indices: additive index, sum of toxic units, and similarity parameter lambda. An analysis of the similarity parameter lambda is done to evaluate whether it has a constant value for IC50-48h, IC10-48h, and IC0-48h. The results suggest that it is quite probable that a constant value of lambda can be used to characterize all response levels, as the isoboles corresponding to the average value of the similarity parameter fit within the 95% confidence intervals of toxicant concentrations at all response levels. The average value of lambda is about 0.80 for the nonylamine-decylamine test and 0.30 for the ethylparathion-decylamine test.

Black River, OH, is contaminated with polycyclic aromatic hydrocarbons (PAHs) from coke ovens of a US Steel Corp. Plant. Closing of a coking plant in 1983 and environmental dredging of the sediments during 1989 and 1990 has reduced the PAH levels significantly. This study quantifies the decrease, and consider source apportionment of PAHs in Black River sediments using chemical mass balance modeling. Five vibra cores collected in 1998 and dated using 210Pb and 137Cs, were analyzed for 18 PAHs. The cores had total PAH concentrations between 250 and 0.10 ppm. PAH maxima occur in 1949, 1969, in accordance with regional historical inputs (core BR4), and in 1991 due to remediation (BR6). Coke oven emissions (CO), highway dust (HWY), and wood burning (WB) are likely sources. The CO source (6-92% of total PAHs) is maximal in 1954, and again in 1992-1994 due to the exposure and redistribution of older contaminated sediments during dredging, and decreases thereafter. There is minimal CO content in 1985 (BR4), 2 yr after closure of the coking plant. The HWY contribution (2-86%) is high during 1969-1988, and increases again after 1993. The WB source is less than 23%, and exhibits a minimum (2%) around 1979 (BR4). There is evidence of aerobic biodegradation or photolysis in the sediment of phenanthrene (PhA) at PhA concentrations >500 ppb.

Polychlorinated biphenyl (PCB) congeners were analyzed in four deep, dated sediment cores from the Ashtabula River (OH, USA), for the purpose of identifying relevant PCB sources and congener patterns. The time span for three of the cores is from the mid 1960s to 1998, whereas the fourth has a time span of six years. The total PCB concentrations are in the range of 0.4 to 6.8 microg/g dry weight, with the highest concentrations observed in samples from the 1970s. A factor analysis (FA) model with nonnegative constraints was used to investigate the sources and patterns of PCBs. Additionally, a new model, based on a least squares method, was developed to identify possible patterns of anaerobic dechlorination of PCBs in the sediments, and to quantify the relevant dechlorination pathways. Both models were validated successfully either by artificially created data sets (FA model) or by using laboratory data from the literature (dechlorination model). The FA model revealed two significant sources. The first was identified as a slightly altered Aroclor 1248. The second did not resemble any Aroclor closely, but was very similar to the overall average congener profile of all samples. Simulation of anaerobic dechlorination on an Aroclor 1248 profile from the literature, according to dechlorination activities H/H', as defined in the literature, yielded a congener profile very similar to that of the second pattern. This indicates the likelihood of anaerobic dechlorination of PCBs in Ashtabula River sediments.

The PCB contamination in lower Fox River sediments was investigated in order to identify possible PCB sources, contributions, and transformations, using two receptor models. Congener specific sediment PCB data from sites immediately upstream of DePere dam to Green Bay that had been gathered for the Green Bay/Fox River Mass Balance Study, were used in this analysis. The first receptor model is a self training factor analysis (FA) model with non-negative constraints that was applied to identify the PCB sources and significant congener patterns. The second is a chemical mass balance model (CMB) in which published Aroclor sources, inferred from our FA model, were used to apportion these Aroclors to each sample. The FA model indicated two significant factors, the major one being Aroclor 1242 and the other, a profile dominated by low chlorinated congeners, indicating a possible PCB alteration profile. This profile had significant contributions to samples at or around sites with total PCB concentrations higher than 50 ppm, indicating a potential anaerobic dechlorination activity. It was also deduced from the FA model that very small contributions of more highly chlorinated Aroclors may be present in the system. The results from the CMB model confirmed that the system is dominated by Aroclor 1242. Its average contribution was 95%, with small amounts of Aroclor 1254 (2%) and 1260 (1%). Two of the samples, located in the vicinity of point sources, showed high contributions of Aroclor 1016 by the CMB model. This is interpreted as an altered Aroclor profile resembling the less chlorinated Aroclor 1016. Contributions obtained form the CMB and FA models show similar patterns.

Carbon particle analysis was performed on a dated sediment core from Lake Erie in order to explore the inputs of pollution from incomplete combustion of coal, oil, and wood. Carbon particles were isolated from the sediment by chemical digestion, and elemental carbon content was determined by CHN analysis. The type of carbon particle (from burning coal, oil, and wood) and particle size and relative abundance were determined using scanning electron microscopy on 100 particles from each core section. The elemental carbon content in the Lake Erie core ranges from 2.5 to 7.4 mg of carbon/g of sediment (1850-1998), and the maximum carbon content in the sediment occurs in the late 1960s to early 1970s. It is shown that particle mass is a better predictor than particle number of historical energy consumption records. This is especially clear for wood where variable particle volumes play a significant role in determining the record of elemental carbon mass from wood burning. Lake Erie core's content of total carbon and carbon particle type is in agreement with U.S. energy consumption records, except that a wood maximum occurs during 1905-1917, about 36 yr after the U.S. consumption maximum from 1870 to 1880.

The PCB pollution in Ashtabula River sediments was evaluated using a factor analysis (FA) model with non-negative constraints, and a chemical mass balance (CMB) model. The FA model identified Aroclor 1248 as the major PCB source, and also a congener pattern significantly different from that of any Aroclor. The CMB model that uses linear combinations of Aroclors, failed to reproduce the sample congener profiles with good statistical fit. The findings from both models indicate that the PCBs in Ashtabula River sediments have undergone significant alterations changing their profiles from those of the original sources. These alterations may be explained by the anaerobic dechlorination of highly chlorinated congeners, according to dechlorination activities H/H'.

The joint toxicity of nonylamine and decylamine and of atrazine and decylamine was evaluated in assays with the green alga Selenastrum capricornutum based on an isobologram method. In this method, curves of constant response, isoboles, are plotted versus concentrations of two toxicants. The response parameter was growth rate based on biomass, and several response levels were used. Dose-response curves were developed for dilution series using fixed ratios between concentrations in toxic units of the compounds. Probit and Weibull dose-response curves were then determined by nonlinear regression. A model for isoboles for partially similar action was used when applicable. The no-effect concentration (NEC or EC0) was estimated based on a newly proposed model containing median effective concentration (EC50) and EC0 as explicit variables. Results show that nonylamine and decylamine are nearly concentration additive at EC50 and EC10 (similarity parameter lambda = 0.70-0.76) and to a lesser extent at EC0. By contrast, the mixtures of atrazine and decylamine show antagonism in that atrazine acts as an antidote to decylamine. The shapes of these isoboles are independent of response level. The EC50 values (mg/L) for chemicals acting singly were 0.090 (nonylamine), 0.039 to 0.044 (decylamine), and 0.225 (atrazine). In order to determine NEC effectively, the level of inhibition must be fairly low, with observed growth rates between 0.6 and 1.0 times the average growth rate of the controls.

A comprehensive analysis of somatic and germline mutations related to DNA mismatch-repair (MMR) genes can clarify the prevalence and mechanism of inactivation in colorectal carcinoma (CRC). In the present study, 257 unselected patients referred for CRC resection were examined for evidence of defective DNA MMR. In particular, we sought to determine the frequency of hereditary defects in DNA MMR in this cohort of patients. MMR status was assessed by testing of tumors for the presence or absence of hMLH1, hMSH2, and hMSH6 protein expression and for microsatellite instability (MSI). Of the 257 patients, 51 (20%) had evidence of defective MMR, demonstrating high levels of MSI (MSI-H) and an absence of either hMLH1 (n=48) or hMSH2 (n=3). All three patients lacking hMSH2, as well as one patient lacking hMLH1, also demonstrated an absence of hMSH6. DNA sequence analysis of the 51 patients with defective MMR revealed seven germline mutations-four in hMLH1 (two truncating and two missense) and three in hMSH2 (all truncating). A detailed family history was available for 225 of the 257 patients. Of the seven patients with germline mutations, only three had family histories consistent with hereditary nonpolyposis colorectal cancer. Of the remaining patients who had tumors with defective MMR, eight had somatic mutations in hMLH1. In addition, hypermethylation of the hMLH1 gene promoter was present in 37 (88%) of the 42 hMLH1-negative cases available for study and in all MSI-H tumors that showed loss of hMLH1 expression but no detectable hMLH1 mutations. Our results suggest that, although defective DNA MMR occurs in approximately 20% of unselected patients presenting for CRC resection, hereditary CRC due to mutations in the MMR pathway account for only a small proportion of patients. Of the 257 patients, only 5 (1.9%) appear to have unequivocal evidence of hereditary defects in MMR. The epigenetic (nonhereditary) mechanism of hMLH1 promoter hypermethylation appears to be responsible for the majority of the remaining patients whose tumors are characterized by defective DNA MMR.

The mitigative effects of the deep tunnel for temporary storage of storm water and sewage, on the water quality of the Milwaukee, Menomonee, and Kinnickinnic Rivers are investigated. The analysis is based on data from the Milwaukee Metropolitan Sewerage District's overflow and surface-water quality monitoring program. Statistical analysis of water quality parameters (BOD, phosphorus, suspended solid, fecal coliform counts, zinc, and chloride) in the three rivers indicates that Menomonee River benefits the most from the deep tunnel. Fecal coliform counts inside the CSO area, and to a certain extent BOD and zinc levels, exhibit the most significant decline after 1994 when the tunnel came on line. These conclusions are based on t-test comparisons of regional averages incorporating spatial and temporal correlations from 1991 to 1993 and 1994 to 1997. The results from t-tests are complemented and confirmed with results from Mann-Kendall tests for trend. Suspended solids and chloride do not decrease after 1994.

Polycyclic aromatic hydrocarbons (PAHs) in dated sediments from Ashtabula River, Ohio, were determined, and a chemical mass balance (CMB) model was used to apportion sources. Three cores (AR-1,AR-2,AR-3) were dated by correlating uranium-supported 210Pb peaks with 1964, 1972, 1977, and 1979 maxima in the discharge record for Ashtabula River. These cores had sedimentation rates between 7.1 and 4.4 cm/year, while a fourth (AR-4) exhibited a much higher rate of 27.8 +/- 18 cm/year. The highest PAH concentration was 11,500 ng/g found in layer 6 of AR-1 (1986), and the lowest was 621 ng/g found in layer 8 of AR-2 (1982). The source contributions to the total PAH concentrations estimated by the CMB model are 0.1-2.2%, 16.8-22.8%, and 78.1-83.8% for wood burning (WB), coke oven (CO), and highway dust (HWY), respectively. Petroleum generated PAHs have maximal contribution during 1977-79, and wood burning PAHs show minimal emissions during 1975-77 in accordance with U.S. consumption records and other studies. Among six PAH markers, only phenanthrene may be subjected to aerobic biodegradation or photolysis with an apparent half-life of 0.005-0.025 year. No anaerobic degradation was observed based on the CMB model. The model works well for the nonmarker compounds, fluoranthene, and benzo[b]fluoranthene/benzo[k]fluoranthene.

Microsatellite instability (MSI) is a genomic alteration observed in 15-30% of colorectal cancer (CRC). Two MSI phenotypes have been defined for CRC: MSI-H is characterized by MSI at > or =30% of the examined loci and MSI-L by MSI at 1-30% of the loci. An absence of MSI at any examined loci has been defined as a microsatellite stable (MSS) phenotype. Current data suggest the majority of MSI tumors are the result of defective DNA mismatch repair (MMR). In this study, we have determined the alpha(1)-antitrypsin deficiency carrier (alpha(1)ATD-ht) status of 161 CRC patients whose MSI phenotype and protein expression states had previously been determined. Cases were selected to enrich a larger number of MSI-H cases. Among 51 CRC patients with MSI-H tumors, the alpha(1)ATD-ht rate was 21.6%; among 110 patients with MSI-L/MSS tumors, the rate was 9.1% (MSI-H vs MSI-L/MSS, P = 0.02); and among the 191 population-based controls the alpha(1)ATD-ht rate was 9.4% (MSI-H vs controls, P = 0.02). The estimated relative risk of having MSI-H CRC among alpha(1)ATD-ht was 3.1 after adjusting for age, gender, and smoking history. The risk of having MSI-H CRC among current and past smokers was 6.6 and 2.7, respectively. Patients who were alpha(1)ATD-ht and smoked had a 20-fold increased risk of developing an MSI-H CRC compared to nonsmokers who were homozygous normal at the alpha(1)ATD locus. Our findings suggest an etiologic link between alpha(1)ATD alleles and development of CRC with defective MMR, and a synergistic effect between smoking and alpha(1)ATD allele in the development of MSI-H CRC., (Copyright 2000 Academic Press.)

Two microsatellite instability (MSI) phenotypes have been described in colorectal cancer (CRC): MSI-H (instability at >30% of the loci examined) and MSI-L (MSI at 1-30% of the loci examined). The MSI-H phenotype, observed in both hereditary nonpolyposis colon cancer-associated CRC and approximately 15% of sporadic CRC, generally results from mutational or epigenetic inactivation of the DNA mismatch repair (MMR) genes hMSH2 or hMLH1. The genetic basis for the MSI-L phenotype, however, is unknown. Several other proteins, including hMSH3 and hMSH6, also participate in DNA MMR. Inactivating mutations of MSH6 in yeast and human tumor cell lines are associated with an impaired ability to repair single-base mispairs and small insertion-deletion loops but not large insertion-deletion loops. This suggests that hMSH6 mutations are more likely to be associated with a MSI-L phenotype than a MSI-H phenotype in CRC. To explore this possibility, we screened tumors from 41 patients with MSI-L CRC for hMSH6 mutations with conformation-sensitive gel electrophoresis (CSGE) and for hMSH6 protein expression by immunohistochemistry. Alterations found with CSGE were confirmed by DNA sequencing of normal and tumor tissue. One somatic (Asp389Asn) and 15 germ-line changes were found. Of the 15 germ-line changes, 9 were found in an intron (none involving splice junctions), and 6 were found in an exon (Gly39Glu, Leu395Val, and 4 silent alterations). Immunohistochemical staining for hMSH6 performed on 34 of the 41 tumors revealed strong nuclear hMSH6 expression in all of the cases. Overall, our results suggest that hMSH6 mutations do not play a major role in the development of sporadic CRC with a MSI-L phenotype.