Sulfur flows and biosolids processing: Using Material Flux Analysis (MFA) principles at wastewater treatment plants.

High flows of sulfur through wastewater treatment plants (WWTPs) may cause noxious gaseous emissions, corrosion of infrastructure, inhibit wastewater microbial communities, or contribute to acid rain if the biosolids or biogas is combusted. Yet, sulfur is an important agricultural nutrient and the direct application of biosolids to soils enables its beneficial re-use. Flows of sulfur throughout the biosolids processing of six WWTPs were investigated to identify how they were affected by biosolids processing configurations. The process of tracking sulfur flows through the sites also identified limitations in data availability and quality, highlighting future requirements for tracking substance flows. One site was investigated in more detail showing sulfur speciation throughout the plant and tracking sulfur flows in odour control systems in order to quantify outflows to air, land and ocean sinks. While the majority of sulfur from WWTPs is removed as sulfate in the secondary effluent, the sulfur content of biosolids is valuable as it can be directly returned to soils to combat the potential sulfur deficiencies. Biosolids processing configurations, which focus on maximising solids recovery, through high efficiency separation techniques in primary sedimentation tanks, thickeners and dewatering centrifuges retain more sulfur in the biosolids. However, variations in sulfur loads and concentrations entering the WWTPs affect sulfur recovery in the biosolids, suggesting industrial emitters, and chemical dosing of iron salts are responsible for differences in recovery between sites.

Brain-derived neurotrophic factor differentially modulates excitability of two classes of hippocampal output neurons.

Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampus-dependent learning and memory. Canonically, this has been ascribed to an enhancing effect on neuronal excitability and synaptic plasticity in the CA1 region. However, it is the pyramidal neurons in the subiculum that form the primary efferent pathways conveying hippocampal information to other areas of the brain, and yet the effect of BDNF on these neurons has remained unexplored. We present new data that BDNF regulates neuronal excitability and cellular plasticity in a much more complex manner than previously suggested. Subicular pyramidal neurons can be divided into two major classes, which have different electrophysiological and morphological properties, different requirements for the induction of plasticity, and different extrahippocampal projections. We found that BDNF increases excitability in one class of subicular pyramidal neurons yet decreases excitability in the other class. Furthermore, while endogenous BDNF was necessary for the induction of synaptic plasticity in both cell types, BDNF enhanced intrinsic plasticity in one class of pyramidal neurons yet suppressed intrinsic plasticity in the other. Taken together, these data suggest a novel role for BDNF signaling, as it appears to dynamically and bidirectionally regulate the output of hippocampal information to different regions of the brain.

Comparison of Two US Sheep Scrapie Isolates Supports Identification as Separate Strains.

Scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats. There are different strains of sheep scrapie that are associated with unique molecular, transmission, and phenotype characteristics. However, in the United States, very little is known about the potential presence of scrapie strains. Scrapie strain and PRNP genotype could both affect susceptibility, potential for transmission, incubation period (IP), and control measures required for eliminating scrapie from a flock. The investigators evaluated 2 US scrapie isolates, No. 13-7 and x124, after intranasal inoculation to compare clinical signs, IPs, spongiform lesions, and patterns of PrPSc deposition in sheep with scrapie-susceptible PRNP genotypes (QQ171). After inoculation with x124, susceptibility and IP were associated with valine at codon 136 (V136) of the prion protein: VV136 sheep had short IPs (6.9 months), those in AV136 sheep were 11.9 months, and AA136 sheep did not develop scrapie. All No. 13-7 inoculated sheep developed scrapie, with IPs of 20.1 months for AA136 sheep, 22.8 months for AV136 sheep, and 26.7 months for VV136 sheep. Patterns of immunoreactivity in the brain were influenced by inoculum isolate and host genotype. Differences in PrPSc profiles versus isolate were most striking when examining brains from sheep with the VV136 genotype. Inoculation into C57BL/6 mice resulted in markedly different attack rates (90.5% for x124 and 5.9% for No. 13-7). Taken together, these data demonstrate that No. 13-7 and x124 represent 2 distinct strains of scrapie with different IPs, genotype susceptibilities, and PrPSc deposition profiles.

Preliminary evaluation of a nonanal lure for collection of gravid Culex quinquefasciatus.

Gravid traps are important tools for disease monitoring and for research on mosquito ovipositional behavior. Two experiments were conducted to evaluate a 2% nonanal lure in gravid mosquito traps in Ifakara, Tanzania. The 1st experiment focused on whether water was needed in the pan below the trap for the nonanal lure to be effective. There was no significant difference between the numbers of gravid females of Culex quinquefasciatus collected in traps using a nonanal lure either with or without water. The 2nd experiment compared the lure, without water, to a grass infusion and a blank trap, without water or attractant. Significantly more mosquitoes were collected in traps with grass infusion than in traps with the other attractants, which were not significantly different from each other. Although more mosquitoes were collected in traps with grass infusion, substantial numbers were also collected in traps with the nonanal lure and unbaited traps.

The Contribution of Postprofessional Doctorates to the Career Development of Healthcare Workers: A Scoping Review.

INTRODUCTION: Doctorate education and implications for career trajectory for postprofessional healthcare workers like physician assistants/associates (PAs) remain under¬studied. PURPOSE: This scoping review identified findings from existing literature on the contribution of postprofessional doctorate (PPD) degrees to the career development of non-entry-level healthcare workers to inform the con¬temporary emergence of PA-specific doctorate programs in the United States. METHODS: The research followed the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Eligible sources examined career advancement outcomes, curriculum, and terminal projects of PPD degree programs for postprofessional healthcare workers. Empirical studies, literature reviews, and commentaries were included. Multiple relevant databases, Google, and Google Scholar were searched. Citation chaining and hand searching of relevant journals were also completed. Screening and data extraction were conducted using Covidence. RESULTS: Among 1,605 sources identified, 24 met eligibility criteria. Most sources examined the Doctor of Nursing Practice and referenced clinical acumen, professional visibility, scholarly capability, leadership readiness, teaching preparation, and self-confidence. CONCLUSION: Findings about PA PPD degrees were limited. Sources exploring other professions demonstrated career development and educational outcomes, making assessment of results challenging. Future research should delineate critical competencies required for doctor¬ate-prepared PAs.

Evaluation of a nonanal-trimethylamine lure for collection of Culex quinquefasciatus (Diptera: Culicidae) in gravid traps.

Gravid traps are useful tools for monitoring vector-borne pathogens in mosquitoes, particularly for those pathogens transmitted by Culex quinquefasciatus Say. One of the primary challenges in the use of gravid traps is the necessity of the inclusion of an oviposition attractant, usually an infusion of organic material, which changes in attractiveness over time. However, a standardized lure, using nonanal and trimethylamine (N + TMA), has been developed and is commercially available. The N + TMA lure was tested against grass infusion and tap water in Tanzania, where Cx. quinquefasciatus is a vector of lymphatic filariasis. Traps baited with grass infusion collected significantly more mosquitoes than N + TMA-baited traps, which collected significantly more than traps baited with tap water. The advantages and disadvantages of the standardized lure are discussed.

Effect of the volume of organic infusion used in gravid traps for collecting Culex quinquefasciatus (Diptera: Culicidae).

Traps that selectively collect gravid mosquitoes have advantages over other collection methods for the purpose of disease surveillance: they trap mosquitoes with a higher probability of carrying disease as they have blood fed on at least one occasion. Gravid traps typically use infusions of organic material to attract gravid mosquitoes, particularly Culex quinquefasciatus (Say). These infusions are heavy and have an unpleasant odor, presenting logistical difficulties for disease monitoring programs. Typically, gravid traps use 4 liters of infusion. The present trial compared the responses of gravid female mosquitoes to 2 and 4 liters of infusion to see if equivalent numbers of mosquitoes could be collected using the smaller volume. In an attempt to better understand the effects of volume of infusion on mosquito oviposition behavior, egg laying on the two volumes was also monitored. There was a significant difference between the mean numbers of egg rafts laid on 2 and 4 liters of infusion. However, the mean numbers of gravid Cu. quinquefasciatus collected in gravid traps with 2 and 4 liters were not significantly different. The results indicate that 2 liters can be used instead of 4 liters for gravid trapping, significantly reducing the cost and logistical difficulties associated with such efforts. The behavioral responses of gravid females to different volumes are also discussed.

Detection of PrPsc in blood from sheep infected with the scrapie and bovine spongiform encephalopathy agents.

The role of blood in the iatrogenic transmission of transmissible spongiform encephalopathy (TSE) or prion disease has become an increasing concern since the reports of variant Creutzfeldt-Jakob disease (vCJD) transmission through blood transfusion from humans with subclinical infection. The development of highly sensitive rapid assays to screen for prion infection in blood is of high priority in order to facilitate the prevention of transmission via blood and blood products. In the present study we show that PrP(sc), a surrogate marker for TSE infection, can be detected in cells isolated from the blood from naturally and experimentally infected sheep by using a rapid ligand-based immunoassay. In sheep with clinical disease, PrP(sc) was detected in the blood of 55% of scrapie agent-infected animals (n = 80) and 71% of animals with bovine spongiform encephalopathy (n = 7). PrP(sc) was also detected several months before the onset of clinical signs in a subset of scrapie agent-infected sheep, followed from 3 months of age to clinical disease. This study confirms that PrP(sc) is associated with the cellular component of blood and can be detected in preclinical sheep by an immunoassay in the absence of in vitro or in vivo amplification.

Using nylon strips to dispense mosquito attractants for sampling the malaria vector Anopheles gambiae s.s.

Synthetic versions of human derived kairomones can be used as baits when trapping host seeking mosquitoes. The effectiveness of these lures depends not only on their attractiveness to the mosquitoes but also on the medium from which they are dispensed. We report on the development and evaluation of nylon strips as a method of dispensing odorants attractive to the malaria vector, Anopheles gambiae s.s. (Giles). When a synthetic blend of attractants was dispensed using this method, significantly more mosquitoes were trapped than when two previous methods, open glass vials or low density polyethylene sachets were used. We conclude that the nylon strips are suitable for dispensing odorants in mosquito trapping operations and can be adopted for use in rural and remote areas. The nylon material required is cheap and widely available and the strips can be prepared without specialized equipment or electricity.

Deficits across multiple behavioral domains align with susceptibility to stress in 129S1/SvImJ mice.

Acute physical or psychological stress can elicit adaptive behaviors that allow an organism maintain homeostasis. However, intense and/or prolonged stressors often have the opposite effect, resulting in maladaptive behaviors and curbing goal-directed action; in the extreme, this may contribute to the development of psychiatric conditions like generalized anxiety disorder, major depressive disorder, or post-traumatic stress disorder. While treatment of these disorders generally focuses on reducing reactivity to potentially threatening stimuli, there are in fact impairments across multiple domains including valence, arousal, and cognition. Here, we use the genetically stress-susceptible 129S1 mouse strain to explore the effects of stress across multiple domains. We find that 129S1 mice exhibit a potentiated neuroendocrine response across many environments and paradigms, and that this is associated with reduced exploration, neophobia, decreased novelty- and reward-seeking, and spatial learning and memory impairments. Taken together, our results suggest that the 129S1 strain may provide a useful model for elucidating mechanisms underlying myriad aspects of stress-linked psychiatric disorders as well as potential treatments that may ameliorate symptoms.

Protective effect of the T112 PrP variant in sheep challenged with bovine spongiform encephalopathy.

Sheep with an ARQ/ARQ PRNP genotype at codon positions 136/154/171 are highly susceptible to experimental infection with bovine spongiform encephalopathy (BSE). However, a number of sheep challenged orally or intracerebrally with BSE were clinically asymptomatic and found to survive or were diagnosed as BSE-negative when culled. Sequencing of the full PRNP gene open reading frame of BSE-susceptible and -resistant sheep indicated that, in the majority of Suffolk sheep, resistance was associated with an M112T PRNP variant (TARQ allele). A high proportion (47 of 49; 96%) of BSE-challenged wild-type (MARQ/MARQ) Suffolk sheep were BSE-infected, whereas none of the 20 sheep with at least one TARQ allele succumbed to BSE. Thirteen TARQ-carrying sheep challenged with BSE are still alive and some have survival periods equivalent to, or greater than, reported incubation periods of BSE in ARR/ARR and VRQ/VRQ sheep.

The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.

The neuronal ceroid lipofuscinoses (NCLs) are the commonest neurodegenerative disorders of children. The aims of this study were to determine the incidence of NCL in Newfoundland, identify the causative genes, and analyze the relationship between phenotype and genotype. Patients with NCL diagnosed between 1960 and 2005 were ascertained through the provincial genetics and pediatric neurology clinics. Fifty-two patients from 34 families were identified. DNA was obtained from 28/34 (82%) families; 18 families had mutations in the CLN2 gene, comprising five different mutations of which two were novel. One family had a CLN3 mutation, another had a novel mutation in CLN5, and five families shared the same mutation in CLN6. One family was misdiagnosed, and in two, molecular testing was inconclusive. Disease from CLN2 mutations had an earlier presentation (p = 0.003) and seizure onset (p < 0.001) compared with CLN6 mutation. There was a slower clinical course for those with CLN5 mutation compared with CLN2 mutation. NCL in Newfoundland has a high incidence, 1 in 7353 live births, and shows extensive genetic heterogeneity. The incidence of late infantile NCL, 9.0 per 100,000 (or 1 in 11,161) live births, is the highest reported in the world.

Emissions of volatile sulfur compounds (VSCs) throughout wastewater biosolids processing.

Volatile sulfur compounds (VSCs) are important contributors to nuisance odours from the processing of wastewater sludge and biosolids. However, emission characteristics are difficult to predict as they vary between sites and are likely to be affected by biosolids processing configuration and operation. VSC emissions from biosolids throughout 6 wastewater treatment plants (WWTPs) in Sydney, Australia were examined in this study. H2S was the VSC found at the highest concentrations throughout the WWTPs, with concentrations ranging from 7 to 39,000µg/m3. Based on odour activity values (OAVs), H2S was typically also the most dominant odorant. However, methyl mercaptan (MeSH) was also found to be sensorially important in the biosolids storage areas given its low odour detection threshold (ODT). High concentrations of VOSCs such as MeSH in the storage areas were shown to potentially interfere with H2S measurements using the Jerome 631-X H2S sensor and these interferences should be investigated in more detail. The VSC composition of emissions varied throughout biosolids processing as well as between the different WWTPs. The primary sludge and biosolids after dewatering and during storage, were key stages producing nuisance odours as judged by the determination of OAVs. Cluster analysis was used to group sampling locations according to VSC emissions. These groups were typically the dewatered and stored biosolids, primary and thickened primary sludge, and waste activated sludge (WAS), thickened WAS, digested sludge and centrate. Effects of biosolids composition and process operation on VSC emissions were evaluated using best subset regression. Emissions from the primary sludge were dominated by H2S and appeared to be affected by the presence of organic matter, pH and Fe content. While volatile organic sulfur compounds (VOSCs) emitted from the produced biosolids were shown to be correlated with upstream factors such as Fe and Al salt dosing, anaerobic digestion and dewatering parameters.

Distribution and sensorial relevance of volatile organic compounds emitted throughout wastewater biosolids processing.

A diverse range of volatile organic compounds (VOCs) are emitted from wastewater biosolids processing. Odorous emissions are predominately made up of volatile sulfur compounds (VSCs) which are typically the only odorants measured. However, a range of VOCs are known to contribute to malodours yet previous studies often overlook the contribution of VOCs in comparison with VSCs. This study aims to evaluate how emissions are affected by different biosolids processing configurations, and if any non-sulfur VOCs should be included in odour measurement and management. Non-sulfur VOCs emitted from biosolids throughout six wastewater treatment plants in the Sydney, Australia region were measured at six locations on average twice each week over 2-3weeks at each site. Variations in types of VOCs emitted throughout and between the sites were assigned to differences in WWTP processing configurations, plant operation and variations in industrial and municipal flows to the sewer network, referred to as sewer catchments. The presence of VOCs is likely due to biotic generation as well as industrial or residential additions to the sewer network. The dewatered and stored biosolids samples had the highest levels of VOC emissions. Sensorially important odorants were p-cresol and butanoic acid, based on the frequency of detection and odour activity values. Other compounds with a high risk of nuisance impacts were trimethylamine, indole and phenol emitted from the dewatered and stored biosolids, and volatile fatty acids from the anaerobic digester inlet and outlet at one particular site. The findings show that non-sulfur VOCs should be added to odorant monitoring campaigns at WWTPs. Identification of VOCs as sensorially important odorants opens opportunities for the more efficient management of nuisance odours, through targeted odour control or process improvement.

A clinical study of 57 children with fetal anticonvulsant syndromes.

BACKGROUND: Anticonvulsants taken in pregnancy are associated with an increased risk of malformations and developmental delay in the children. To evaluate the pattern of abnormalities associated with prenatal anticonvulsant exposure further, we undertook a clinical study of 57 children with fetal anticonvulsant syndromes. METHODS: Fifty two children were ascertained through the Fetal Anticonvulsant Syndrome Association and five were referred to the Aberdeen Medical Genetics Service. Pregnancy and medical history were obtained through a standardised questionnaire and interview and the children were examined. RESULTS: Thirty four (60%) were exposed in utero to valproate alone, four (7%) to carbamazepine alone, four (7%) to phenytoin alone, and 15 (26%) to more than one anticonvulsant. Forty six (81%) reported behavioural problems, 22 (39%) with hyperactivity or poor concentration of whom four (7%) had a diagnosis of attention deficit and hyperactivity disorder. Thirty four (60%) reported two or more autistic features, of whom four had a diagnosis of autism and two of Asperger's syndrome. Forty four (77%) had learning difficulties, 46 (81%) had speech delay, 34 (60%) had gross motor delay, and 24 (42%) had fine motor delay. Nineteen (33%) had glue ear and 40 (70%) had joint laxity involving all sizes of joints. Of 46 who had formal ophthalmic evaluation, 16 (34%) had myopia. CONCLUSIONS: Speech delay, joint laxity, glue ear, and myopia are common in the fetal anticonvulsant syndromes and autistic features and hyperactivity form part of the behavioural phenotype.

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth.

OBJECTIVE: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. DESIGN: Retrospective population based study. SETTING: Population of the Grampian region of Scotland. PARTICIPANTS: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. MAIN OUTCOME MEASURES: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. RESULTS: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). CONCLUSION: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.

Risk factors for mortality in cattle during live export from Australia by sea.

OBJECTIVE: This study investigated mortality trends and risk factors for death for cattle exported live from Australia by sea. METHODS: Mortality data for all voyages from Australia to all destinations between 1995 and 2012 were analysed retrospectively. Daily mortality trends were assessed for 20 long-haul voyages from Australia to the Middle East and to the Russian Federation between 2010 and 2012. RESULTS: The overall voyage mortality percentage was 0.17% across the 13 million cattle exported on 6447 voyages. Mortality rates decreased significantly after 2000 and stabilised at low levels from 2003. The mortality rate for voyages to the Middle East and north Africa (0.44%) was significantly higher than for voyages to south-east Europe (0.28%), north-east Asia (0.12%) and south-east Asia (0.09%). Cattle exported from ports in southern Australia carried a higher mortality risk than those exported from northern ports for both long- and short-haul voyages. The daily mortality rate on long-haul voyages peaked at 3-4 weeks post-departure, although there was a smaller peak at 1-2 weeks. CONCLUSION: The marked reduction in mortality rate since 2000 is related to a number of factors, including industry initiatives, government legislation and market demand, that have resulted in changes to both the selection of cattle for export and the management of cattle prior to and during voyages. Routine collection of animal performance data, combined with NLIS records and use of methods described here, have the potential to contribute to more effective management of mortality risks across the export chain.

Cytotoxic effects of singlet oxygen.

The toxic effects of gas-phase singlet oxygen, 1O2, on the ciliated respiratory epithelium of hamster trachea have been demonstrated. Tracheal explants treated with 1O2 showed a dose-dependent decrease in cilia beating frequency and focal ciliostasis. A statistically significant decrease in ciliary activity occurred at 1O2 concentrations as low as 154 ppb after a 2-hr exposure. Cytological alterations in the mucociliary epithelium were observed in explants exposed to 235 ppb 1O2 or greater. When cytotoxic effects were related to the time of exposure to 1O2, maximum effects occurred after a 4-hr exposure. In vitro recovery studies indicate that ciliary activity returned to normal between 4 and 8 hr after exposure.

The early ontogeny of the afferent nerves and papillary ridges in human digital glabrous skin.

The present study examines the early ontogeny of afferent nerves in human embryonic glabrous digital skin and documents the onset of cutaneous innervation and papillary (sweat duct) ridge formation by light and electron microscopy. The skin examined in this study was taken from 3 developmental stages of decreasing embryonic age: embryos older than 10 weeks estimated gestational age (EGA) representing the period of primary ridge formation, embryos of 8-9 weeks EGA representing the period immediately prior to ridge formation; and embryos 6-8 weeks EGA representing the period weeks before the onset of ridge formation. The earliest papillary ridges are present in 10 week EGA embryos, with small ridges present in two sites: the center of the proximal third and also at the tip of the distal phalangeal or apical pad. These papillary ridges typically contained Merkel cells. Papillary ridges formed progressively in a radial manner from these central foci. The proximal focus corresponds to the geometric center of the mature dermatoglyphic pattern of loops, arches, or whorls. This radial wave of ridge differentiation is discontinuous with the abrupt cessation of ridge formation responsible for the discontinuities in the mature papillary ridges and the corresponding dermatoglyphic print. Skin over the proximal and middle phalanges developed papillary ridges beginning in the 12th week. No papillary ridges could be identified in embryos of 8-9 weeks EGA, but a large number of growth cones are present in the superficial dermis subjacent to differentiating Merkel cells. The basal lamina of the epidermis was discontinuous wherever growth cones abutted Merkel cells. Merkel cells not directly associated with axons were also present in the epidermis of embryos of 8-9 weeks EGA. The embryos of 6-8 weeks EGA lack any sign of Merkel cells and/or melanocytes, but developing neurovascular bundles with axonal growth cones near the epidermis could be identified by light and electron microscopy. Presumptive Schwann and perineural cells are also seen in the dermis. We conclude that the developing afferent nerve fibers provide a grid which influences the temporal and/or spatial factors involved in the sequential onset and cessation of formation of papillary ridges. Thus the dermatoglyph can reflect the ontogeny of the afferent nervous system that occurred prior to papillary ridge development. These observations lend support to the concept that successive waves of afferent neural development have an important role in the spatial and temporal sequence of papillary ridge formation and thus the formation of both the dermatotopic map of the digits and the dermatoglyph.

Synergistic lethality induced by the combination of carbon monoxide and cyanide.

Carbon monoxide (CO) and hydrogen cyanide are recognized pyrolytic products of plastic materials in fires. Lethal blood concentrations of CO and cyanide are found in fire victims and considered to be the cause of death. However, there are reports of fire victims with sublethal concentrations of both CO and cyanide and no other attributed reason for their deaths. Thus, the purpose of this study was to investigate lethality induced by low concentrations of CO and cyanide. Male ICR mice were used in these studies. Doses of potassium cyanide (4-9 mg/kg, i.p.) were administered to animals pretreated for 3 min with either air or CO (0.63-0.66%). From these data the LD50 value of potassium cyanide (KCN) was determined in these animals pretreated with either air or CO. A significantly lower LD50 value for KCN was found in CO-pretreated animals as compared to air-pretreated animals. In another series of experiments, animals were pretreated with either saline or KCN (1.00-6.35 mg/kg, i.p.) and then placed in the chamber containing a CO atmosphere (0.325-0.375%). Ten to 20% of saline-pretreated animals were dead at the end of the monitoring period. Sublethal doses of KCN (3.5-6.35 mg/kg, i.p.) produced a synergistic lethality as compared to the saline-pretreated animals. Blood was analyzed for CO and cyanide content to determine if there were any changes that could explain this augmented lethality. There was no difference in CO or cyanide blood concentrations between these treatment groups. From these data there was demonstrated a synergistic lethality induced by the combination of CO and cyanide that could not be explained by altered CO or cyanide blood concentrations.