bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do General Practitioners Respond to Reports of Abnormal Chest X-rays?
Authors: Lim W S , Macfarlane J T , Deegan P C , Manhire A , Holmes W F , Baldwin D R
Published: May 2017

General practitioners (GPs) in the UK have long had direct access to hospital radiological services, which in theory shortens investigation time and improves the quality of service. Chest X-rays (CXRs) account for a substantial proportion of requests, and we investigated what happened when an abnormality was detected.

In one year, 204 GPs in the Nottingham area requested CXRs in 605 patients. 362 were reported normal, 165 abnormal but hospital follow-up not indicated and 71 abnormal with radiological follow-up or hospital referral indicated (mass lesion suspicious of tumours 27, infective shadowing 35, other 9). 64 of the 71 were seen in hospital within three months, and in those with suspected cancer the median time to follow-up was 20 days.

These results show that GPs do act on the results of abnormal CXRs, but only 37% of those with a mass suspicious of cancer were seen in hospital within two weeks as recommended by the British Thoracic Society. Time might be saved if GPs agreed to direct referral from the radiology department to respiratory physicians.
Traumatic pseudocyst of the spleen
Authors: Sinha P S , Stoker T A M , Aston N O
Published: May 2017

Four patients with pseudocyst of the spleen gave histories of abdominal trauma. In one patient the pseudocyst had ruptured, necessitating emergency splenectomy 34 years after the original injury. In a second patient the pseudocyst was discovered incidentally, and was managed by spleen-preserving excision; and the third and fourth presented with abdominal pain and had splenectomy and spleen-preserving surgery, respectively.

All patients with conservatively treated splenic injury are at risk of developing a pseudocyst of the spleen, and the lesion can be detected by computed tomography or ultrasound. When there are no symptoms the natural history is unknown; but if surgery is necessary, splenectomy can sometimes be avoided.
Attitudes to organ donation among South Asians in an English high street
Authors: Ahmed Wasim , Harris Susie , Brown Edwina
Published: May 2017

In the UK, people of South Asian origin are at more than twice the risk of end-stage renal failure encountered in the Caucasian population but are under-represented among organ donors. Difficulties with matching mean that few donated kidneys are suitable for transplantation to South Asian recipients. A survey of attitudes in 100 South Asian adults was conducted in the main street of Southall, Middlesex. 90 of those questioned were aware of organ transplantation and 69 had heard about donor cards. However, the 16% who carried a donor card was lower than the 28% reported in the general population. The main reason for the low organ donation rate by South Asians seemed to be lack of knowledge, and this could be remedied by more targeting of information in the Asian media.
Composite hierarchical anti-disturbance control for stochastic systems with multiple disturbances
Authors: Sun Shixiang , Wei Xinjiang , Zhang Huifeng
Published: May 2017

A class of stochastic systems with multiple disturbances, which includes white noises and disturbances whose time derivative is bounded, is considered in this paper. To estimate the unknown bounded disturbance, a stochastic disturbance observer is proposed. Based on the observer, a disturbance observer-based disturbance control scheme is constructed such that the composite closed-loop system is asymptotically bounded. Finally, a simulation example is given to demonstrate the feasibility and effectiveness of the proposed scheme.
Nonlinear H-infinity control for 4-DOF underactuated overhead cranes
Authors: Rigatos Gerasimos , Siano Pierluigi , Abbaszadeh Masoud
Published: May 2017

The article proposes a nonlinear H-infinity control method for four degrees of freedom underactuated overhead cranes. The crane’s system is underactuated because it receives only two external inputs, namely a force that allows the motion of the bridge along the x-axis and a force that allows the motion of the trolley along the y-axis. A solution to the control problem of this underactuated system is obtained by applying nonlinear H-infinity control. The dynamic model of the overhead crane undergoes approximate linearization round local operating points which are redefined at each iteration of the control algorithm. These temporary equilibria consist of the last value of the crane’s state vector and of the last value of the control signal that was exerted on it. For the approximate linearization of the system’s dynamics, a Taylor series expansion is performed through the computation of the associated Jacobian matrices. The modelling errors are compensated by the robustness of the control algorithm. Next, for the linearized equivalent model of the crane an H-infinity feedback controller is designed. This requires the solution of an algebraic Riccati equation at each iteration of the computer control program. It is shown that the control scheme achieves H-infinity tracking performance, which implies maximum robustness to modelling errors and external perturbations. The stability of the control loop is proven through Lyapunov analysis.
On the estimation and control of human body composition
Authors: Karimi Mahmood , Rao Ramesh R
Published: May 2017

Obesity is a chronic disease that can lead to an increased risk of other serious chronic diseases and even death. We present switching and time-delayed feedback-based model-free control methods for the dynamic management of body mass and its major components. The estimation of body composition based on human body weight dynamics is proposed using a soft switching-based observer. Additionally, this paper addresses the control allocation problem for optimal body weight management using linear algebraic equivalence of the nonlinear controllers based on dynamic behaviour of body composition described in literature. A control allocator system computes the required energy intake and energy expenditure from a controlling range of inputs to track the desired trajectory of body mass by optimizing a weighted quadratic function. Simulation results validate the performance of the proposed controllers and the observer under disturbances in energy intake and energy expenditure.
Performance Criticism: An Emerging Methodology in Second Testament Studies—Part I
Authors: Rhoads David
Published: May 2017

This paper argues for the centrality of performance in the life of the early church, an area of study that has been traditionally neglected. In light of some emerging trends, it proposes that we establish “performance criticism” as a discrete discipline in New Testament studies to address this neglect. Performance criticism would inform in fresh ways our understanding of the meaning and rhetoric of the Second Testament writings and our re-constructions of early Christianity. Because it represents a medium change, performance criticism has the potential to impact the way we do biblical studies in general. Finally, performance could breathe new life into the experience of the Bible in the contemporary world. In Part 1, I lay out some features of oral cultures, the potential interplay between written and oral media, and the origins in orality of Second Testament writings. Then, I seek to identify the various features of a performance event—performer, audience, material setting, social circumstances, and so on—as a basis to construct and analyze performance as the site of interpretation for Second Testament writings. In Part 2, I show how performance criticism could draw upon resources from many established and some new disciplines of biblical scholarship as contributors to performance criticism. Finally, I suggest that performance criticism might engage the interpreter in the actual performing of texts, and I lay out the potential research benefits of such an exercise.
Investigating the Behaviors of M2 and RMSEA2 in Fitting a Unidimensional Model to Multidimensional Data
Authors: Xu Jie , Paek Insu , Xia Yan
Published: May 2017

It has been widely known that the Type I error rates of goodness-of-fit tests using full information test statistics, such as Pearson’s test statistic χ2 and the likelihood ratio test statistic G2, are problematic when data are sparse. Under such conditions, the limited information goodness-of-fit test statistic M2 is recommended in model fit assessment for models with binary response data. A simulation study was conducted to investigate the power and Type I error rate of M2 in fitting unidimensional models to many different types of multidimensional data. As an additional interest, the behavior of RMSEA2 was also examined, which is the root mean square error approximation (RMSEA) based on M2. Findings from the current study showed that M2 and RMSEA2 are sensitive in detecting the misfits due to varying slope parameters, the bifactor structure, and the partially (or completely) simple structure for multidimensional data, but not the misfits due to the within-item multidimensional structures.
Differential diagnosis of a rare papillary tumor and mucinous adenocarcinoma
Authors: Matsuoka Shunichiro , Kondo Ryoichi , Ishii Keiko
Published: May 2017

Ciliated muconodular papillary tumors are characterized as rare papillary tumors of the peripheral lung, and involve ciliated, goblet, and basal cell proliferation with mucin secretion. We report the case of a 76-year-old woman who had an irregular solid nodule in the lung on chest computed tomography during a health screening. A wedge resection was performed. Although the intraoperative cytological diagnosis was mucinous adenocarcinoma, the final histological diagnosis was ciliated muconodular papillary tumor. The postoperative course was uneventful, with no recurrence at 24 months after surgery. Cytological diagnosis of ciliated muconodular papillary tumor can be difficult because of its similarity to mucinous adenocarcinoma.
Terminology and Classification of Congenital Vascular Malformations
Authors: Lee B B , Laredo J , Lee T S , Huh S , Neville R
Published: May 2017

Venous malformation (VM) is a congenital vascular malformation (CVM) that develops along the venous system through the various stages of embryogenesis. Older terminology and classification were often misleading and confusing. A newer classification system has emerged that is based on advances in the study of these conditions and is useful in contemporary management. The Hamburg classification was introduced after reappraisal of older terminology and has become the standard system for contemporary classification, which is based on anatomical, pathological and embryological criteria.
Klippel–Trenaunay Syndrome: Current Management
Authors: Glovkzki P , Driscoll D J
Published: May 2017

Klippel–Trenaunay syndrome (KTS) is a rare, sporadic, complex malformation characterized by the clinical triad of (1) capillary malformations (port wine stain); (2) soft tissue and bone hypertrophy or, occasionally, hypotrophy of usually one lower limb; and (3) atypical, mostly lateral varicosity. KTS is a mixed vascular malformation, with predominant capillary, venous and lymphatic components, without significant arteriovenous shunting. Management is largely conservative and the extent of diagnostic evaluation is determined by the planned treatment. Compression is the hallmark of conservative management; laser can be used to treat port wine stains. Imaging before vascular interventions must confirm venous anatomy and deep venous drainage. Techniques for ablation of superficial veins and malformations are individualized and may include sclerotherapy with alcohol or foam, endovenous thermal ablation or, as used most frequently in our practice, surgical stripping and phlebectomy. Intraoperative use of tourniquet will decrease bleeding, selective use of an inferior vena cava filter will prevent pulmonary embolism. A multidisciplinary approach to management of KTS is warranted.
Masking the Identities of Celebrities and Personally Familiar Individuals: Effects on Visual and Auditory Recognition Performance
Authors: Krix Alana C. , Sauerland Melanie , Schreuder Maartje J.
Published: May 2017

The current study compared the effectiveness of masking on recognition performance for faces and voices of celebrities and personally familiar individuals. On the basis of the theory suggesting stronger memory representations for personally familiar individuals, we expected masking to be more effective for celebrities than for personally familiar stimulus persons. Furthermore, we sought to replicate the face recognition advantage with masked stimuli. Face pixelation and electronic changes of the voice pitch were applied as masking techniques, using four masking levels for each stimulus. Thirty-one undergraduate students were presented with the masked faces and voices of 10 celebrities and 10 personally familiar fellow students. As expected, more correct recognitions occurred for faces than for voices, suggesting that masking does not counteract the mechanisms causing the face recognition advantage. Unexpectedly, masking effectiveness did not differ between celebrities and personally familiar individuals. This may be due to the type of personally familiar individuals used. Within personally familiar stimuli, increased familiarity did not predict the effectiveness of masking. Whereas the highest masking level eliminated speaker recognition, masking did not fully eliminate face recognition. From a practical perspective, the findings especially question the suitability of pixelation as a means for identity concealment.
Cyclic Creep Damage in Thin-Walled Structures
Authors: Altenbach H , Breslavsky D , Morachkovsky O , Naumenko K
Published: May 2017

Thin-walled structural elements are often subjected to cyclic loadings. This paper presents a material model describing creep behaviour under high-cycle loading conditions (N ≥ 5 × 104-105). Assuming that the load can be split into two joint acting parts (a static and a superposed, rapidly varying small cyclic component), the asymptotic expansion of two time-scales has been applied to the governing equations of the initial-boundary value creep problem. The system of equations determine two problems. The first is similar to the creep problem by quasi-static loading. The second is the problem of forced vibrations. Both the problems are coupled by constitutive equations. The model is applied to the simulation of the cyclic creep damage behaviour of thin-walled structural elements. The results are discussed for two special numerical examples (a conical shell and a circular plate). The simulations show that the creep and the damage rates as well as the failure time are strongly sensitive to the redistribution of the stress state cycle asymmetry parameter As. The values of As increase during the creep process. For particular cases of the loading frequency, As can exceed the critical value. In this case the material model must be extended in order to consider the creep-fatigue damage interaction.
Effects of Bur Wear during Implant Site Preparation: An in Vitro Study
Authors: Scarano A. , Carinci F. , Quaranta A. , Di Iorio D. , Assenza B. , Piattelli A.
Published: May 2017

Background: Few studies have investigated the influence of drilling on bone healing. After the drilling of bone and placement of dental implants a sequence begins of cellular and molecular events which represents a combined response of wound healing. The bone healing around dental implants is a complex phenomenon and influences the proliferation and differentiation of pre-osteoblasts into osteoblasts, together with the activation of periosteal and endosteal lining cells, and initiates the production and mineralization of osteoid matrix followed by the organization of the bone-implant interface. The objective of this study is to quantify the temperature changes in cortical bone and marrow spaces during implant site preparation in bovine rib bone. A total 10 harvested bovine ribs and 6 10.5 × 3.5 new drills for implant insertion with external irrigation (Bone System, Milano, Italy) were used in this study. The implant sites were prepared with 10 mm long drills at 500 rpm under abundant external irrigation with saline solution at 37°C. Each drill was used for 10, 30, 60, 90 and 120 implant site preparations; each drill was then observed under SEM for evaluation of the damage of the cutting edge after 10, 30, 60, 90 and 120 preparations. There was an higher and statistically significant increase in the temperature in the cortical bone; this increase in temperature increases with the number of the times of drill use. The drill wear seemed to play a major role in heat production and could explain the observed increased temperature of the bone.
Removal Torque Values of Titanium Implants Inserted into Bone Defects Filled with Hydroxyapatite: A Histologic and Histomorphometric Analysis in Rabbit
Authors: Scarano A. , Carinci F. , Mangano C. , Quaranta A. , Piattelli A.
Published: May 2017

The successful clinical use of implants with microrough titanium surfaces has paved the way for the further development of surface topographies to promote enhanced peri-implant bone apposition during the early stages of bone regeneration. The aim of this study is to determine the torque resistance of the implant-bone interface of plasma sprayed titanium endosseous implants placed in the rabbit tibia in three different situations. Hydroxyapatite (HA) particles with a size ranging from 250 to 450 μm were used in the present study to fill out 6 mm bony defects created in rabbit tibia. Fourteen mature New Zealand white male rabbits, weighing about 2.5 Kg., were used in this study. The test sites were filled with HA and the non-grafted sites were used as control. A total of 28 bone defects (14 without HA and 14 with HA.) were created. Implants with plasma-spray surface were subsequently inserted. Six additional rabbits were used; in these animals no bone defects were created. The implant sites were divided into three groups: 1) implants inserted in the tibia without bone defects; 2) implants inserted in the tibia with bone defects not filled with HA; 3) implants inserted in the tibia with bone defects filled with HA particles. The purpose of this study is to measure reverse-torque in three different situations of clinically similar implant geometry in the articulation of rabbits. The null hypothesis stated that there is a difference in reversal torque between the bone regeneration with HA, native bone and bone defect without bone regeneration. Additionally, comparison between these 6-month data and the 3-month data from a previous study led to the following conclusions: a significant difference exists in the removed torque for the TPS implants in the bone regenerated by HA and native bone; increase in removal torque values was seen for the implant inserted in bone regenerated by HA compared to the implant nated in bone without biomaterials. In conclusion, bone regenerated with biomaterials possesses different mechanical characteristics to native bone.
Vascular Endothelial Growth Factor Expression (VEGF) in Salivary Glands of Diabetic Rats
Authors: Perrotti V. , Piattelli A. , Piccirilli M. , Bianchi G. , Di Giulio C. , Artese L.
Published: May 2017

This study is aimed at evaluating vascular endothelial growth factor (VEGF) expression in the salivary glands of diabetic rats. Our study was carried out on 1 group of male Wistar rats and 1 group of male Bio Breeding Wistar (BB/W) pre-diabetic rats. The first group (control) was composed of 11 rats (4 months old), and the other (test) of 11 rats (4 months old) which showed diabetes at day 85 of life. This kind of diabetes can be compared to human diabetes mellitus type 1. The submandibular glands were removed and processed for immunohistochemical analysis of VEGF. Diabetes increased salivary gland VEGF expression in the rats. The tissues analyzed (vascular endothelium, ductal endothelium, mucinous glands) always expressed VEGF, thus demonstrating that not only vascular endothelial cells, but also the other elements evaluated, have a role in the neoangiogenesis process. In both control and diabetic rats, the VEGF expression was constantly negative only in serous acini; thus demonstrating that serous acini are not involved in the neoangiogenetic processes. The vascular growth is a fundamental part of normal salivary gland development, therefore we speculate that strategies aimed at preservation or promotion of salivary gland VEGF expression may mitigate or attenuate diabetic-induced gland microvascular injury.
Role of the Friction Free Distalize Appliance (2FDA)Pat in the Molar Distalization: Photoelastic Analysis and Alkaline-Phosphatase (ALP) Activity on First Molar and Bicuspid
Authors: D'attilio M. , Tecco S. , Traini T. , Spoto G. , Festa F.
Published: May 2017

Maxillary molar distalization is an increasingly popular option for the resolution of Class II malocclusions. This study describes the effects of one particular molar distalizing appliance, the Friction Free Distalize Appliance (2FDA), in a sample of 20 consecutively treated and growing patients to verify the osteoblastic activity in the compression and traction sites of both the molars and the bicuspids when used as the anchorage teeth. The 2FDA appliances were constructed utilizing a Nickel Titanium open coil spring of 200 gr force in order to distalize the maxillary first molar. The reaction force was controlled utilizing the principle of low/free friction. The results show that the resin around the root of the bicuspid did not discolour at all, which indicates an absence of a force load. On the other hand, on the molar, the resin around the root of the molar became discoloured due to the fact that an orthodontic force was involved with the tooth. To better understand whether the quantity of force that reached the tooth was able to produce osteoblastic recruitment in the sites of tension of the molar and the bicuspid, we quantified an enzyme, the alkaline phosphatase (ALP), present. This measurement allowed us to verify a regular increase of the ALP on the site of molar traction. We also elaborated a mathematical model to evaluate the quantity of force of reaction that produces the device on the bicuspid. Such force results as being 8.34 grams which equals half the pressure of the capillaries of the parodontal ligament (18 grams). The 2FDA appliance compares favourably with other intra-oral distalization devices for the resolution of patients with Class II malocclusions, and is the only distalizing appliance that does not determine osteoclastic/osteoblastic recruitment on the “anchorage tooth”.
Pharmacologic Modulation of Clodronate in Local Therapy of Periodontal and Implant Inflammation
Authors: Volpi R. , Rossi F. , Trisi P. , Testori T. , Berardi D. , Perfetti G.
Published: May 2017

Bisphosphonates are drugs used in the treatment of a variety of osteometabolic diseases. Recently they have been the object of research and studies on their potential application in dentistry and orthopedics. In particular, clodronate (non-aminobisphosphonates) has been studied, due to its reversible activity in comparison to apoptotic osteoclasts, the intrinsic action which stimulates the differentiation and activity of the osteoblasts, their antinflammatory activity, antipain and antioxidant action, represent the rational to estimate their clinical efficacy, for local use in dentistry, implatology, orthopaedic, rheumatology, oncology and dermatology.
Dental Pulp Stem Cells Bioadhesivity: Evaluation on Mineral-Trioxide-Aggregate
Authors: Trubiani O. , D'arcangelo C. , Di Iorio D. , Di Nardo Di Maio F. , Caputi S.
Published: May 2017

Stem cells are undifferentiated cells that have the capacity to self-renew. They have been discovered in many adult tissues, including teeth. Dental Pulp Mesenchymal Stem Cells (DP-MSCs) are involved in dental repair by activation of growth factors, released after caries and have the ability to regenerate a dentin-pulp-like complex. The molecular/cellular research gives the possibility to grow new tissues and biological structures for clinical applications, providing cells for therapies including cell transplantation and tissue engineering. In this study DP-MSCs were derived from dental pulp of 10 donors. To evaluate material toxicity, after in vitro isolation, the cells were seeded on mineral trioxide aggregate (MTA). Initial light microscopy investigation of cells revealed no signs of cell death due to toxicity or infection, on the contrary the scaffolds supplied an excellent support for cell structures, the cells proliferated and adhered to substrate. Similar observation was seen in scanning electron microscopy, in particular the cells had proliferated and spread, covering a considerable part of the surface of the biomaterials investigated, with an elaborate form of attachment, in fact, the cells formed a continuous layer on the upper surface of the MTA. In conclusion, the aim of this study is to demonstrate that DP-MSCs combined with MTA could be a potential source for regenerative medicine, encouraging further study to evaluate the new-dentin formation.
Material orthotropy effects on progressive damage analysis of open-hole composite laminates under tension
Authors: Zhou Song , Sun Yi , Chen Boyang , Tay Tong-Earn
Published: May 2017

The sizes effects on the strengths of open-hole fibre-reinforced composite laminates subjected to tensile loading (OHT) have been investigated widely. However, little attention has been paid to the influence of material orthotropy. This paper presents a progressive damage model for the model failure of notched laminates under tensile loading based on continuum damage mechanics and cohesive elements. The effects of orthotropy on the failure of notched laminates with seven different ply sequences are investigated by our proposed model. The prediction results adopting the Hoffman and Pinho failure criterions to determine matrix damage initiation are compared with the results of experiments. Our proposed models are able to predict the strong influence of orthotropy on strengths of open-hole laminate under tension, and model using Pinho criterion can predict the open-hole tension strength most accurately.
Assessment of Carbamate Pesticide Immunotoxicity
Authors: Thomas Peter T. , Ratajczak Helen V.
Published: May 2017

Adult female Swiss Webster and B6C3F1 mice received distilled water only or water containing 0.1, 1.0, 10, 100 or 1000 ppb of aldicarb daily for 34 days. The target concentration of aldicarb present in the 10 ppb dosing solution was analytically verified on a daily basis as was its stability over a 48-hr period. To develop an immune profile of this compound, functional parameters measured after exposure included resistance to infectious viral challenge; quantitation of splenic antibody-forming cells to sheep erythrocytes; splenic lymphocyte blastogenesis to B-cell mitogens; and T-cell mixed lymphocyte culture response. In addition, gross and histopathologic examinations of tissues relevant to the immune system were performed. The absence of significant effects on any of these parameters suggests that aldicarb at environmentally relevant exposure concentrations is not immunotoxic in rodents.
Food and Drug Administration: Approach to Evaluating Neurotoxicity
Authors: Sobotka Thomas J.
Published: May 2017

One of the primary features of the mission of the Food and Drug Administration is to assure with reasonable certainty that no harm will result from the intended use of chemicals added to food. In carrying out this mission the FDA uses a structured process to assess the safety of each food chemical. The detailed mechanics of this process are described in an FDA document entitled “Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Use in Food” (Food and Drug Administration, 1982). Central to its evaluation the FDA requires a collective set of information, including estimates of the anticipated human exposure to the food chemical and a broad-based toxicological profile. Certainly, any adverse effect observed in the nervous system is recognized as an important element in the determination of chemical safety and follow-up information which would enable an assessment of such an effect to be included in the toxicological profile. The agency's current approach to evaluating neurotoxicity should be viewed within the context of its overall strategy for the safety assessment of food chemicals. Four basic premises underlie the FDA's approach to safety assessment.
Human Neurobehavioral Toxicology Testing: Current Perspectives
Authors: Anger W. Kent
Published: May 2017

Standardized tests or test batteries for neurotoxic effects are needed for premarket testing of chemicals (and related regulatory needs) and for the development of a neurotoxicity data base. Three widely known human test batteries based on past research findings and developed to screen for a broad range of neurotoxic effects are currently in use. One was developed by Finland's Institute of Occupational Health, one was recently recommended by the World Health Organization, and one was recently developed as a computer-implemented battery by US researchers. Each of these batteries assesses many frequently occurring neurotoxic effects, but each is limited by the lack of tests for some motor and sensory functions and affective responses that often occur following chemical exposures. Problems with field or worksite assessments using these test batteries involve age, education, socioeconomic, and job differences between exposed and comparison groups, and the lack of normative data on these batteries. To address some of these problems, the human neurobehavioral test batteries are currently undergoing reliability or validity assessments on a national and international scale. This will provide an assessment of their utility and accelerate development of a data base of neurotoxic effects of chemicals.
Adoption of New Guidelines and Data Requirements for More Extensive Neurotoxicity Testing under Fifra
Authors: Sette William F.
Published: May 2017

In 1987 the Center for Science in the Public Interest (CSPI) and others petitioned EPA to, “issue testing methods necessary to fully assess the neurotoxic and neurobehavioral effects of pesticide active and inert ingredients. ” In response OPP convened a meeting of an expert subpanel on neurotoxicity of the Scientific Advisory Panel to review its proposed response. The petitioners proposed specifically that OPP use the neurotoxicity guidelines developed by EPA's own Office of Toxic Substances. They asserted that the scope of potential neurotoxic hazards is broad and that current guidelines will neither adequately identify nor characterize these effects. A series of expert panels have endorsed the use of more extensive neuropathological evaluations, better clinical examinations, explicit unconditioned and conditioned behavioral testing, testing of prenatally exposed animals for neurological deficits, and development of a means for evaluation of the broad range of potential neurotoxic effects. In response to this petition the following additions to the assessment of pesticides were proposed by OPP and approved by the SAP: expanded functional observation neuropathology, and motor activity into an acute and subchronic screening battery; addition of tests of operant behavior or other tests of sensory or cognitive function as conditional data requirements; and addition of a conditional requirement of postnatal neurofunctional and neuropathological evaluation of offspring.
Critical Assessment of Motor Activity as a Screen for Neurotoxicity
Authors: Maurissen Jacques P. J. , Mattsson Joel L.
Published: May 2017

Motor activity consists of a large number of motor behaviors not placed under stimulus control. The Environmental Protection Agency defines motor activity in terms of “activity counts, ”and has incorporated it in the guidelines for the assessment of neurotoxicity. While motor activity testing has some enticing operating characteristics, a dose-related change in activity counts can reflect an effect on the nervous system only in the absence of systemic toxicity. Furthermore, when a motor activity effect has been documented, ancillary data or further testing is needed to determine whether this effect is indeed adverse. In addition, the results of a motor activity test do not usually provide information about either the origin of the problem, or the follow-up tests that need to be conducted.
Correlation of Cerebral Cortical Morphology with Behavior
Authors: Norton Stata
Published: May 2017

Association between functional damage and damage to the central nervous system from toxic agents can be used to determine the value of behavioral tests as predictors of damage to the nervous system. Variability in data from behavioral tests may be caused, in part, by varying levels of structural differences in the nervous system. Stepwise multiple regression is one method for analyzing the relationship between variability in data resulting from linkage between functional and morphological or other parameters of the structure of the nervous system. As an example, the predictive value of four behavioral tests is assessed in detecting thinning of the cerebral cortex following gestational exposure of rats to ionizing radiation. In this analysis, there were seven independent variables for predicting cortical thickness. The sequence of number of times each variable was used in prediction, from most frequent to least frequent, was: angle of stride > negative geotaxis > continuous corridor> body weight > width of stride > length of stride > reflex suspension. The data support the concept that there are varying degrees of predictive associations between these functional and cortical parameters.
Effect of Lead on the Stromal Cells of Bone Marrow in Rats in Vitro
Authors: Miszta Helena
Published: May 2017

The effect of lead on the stromal cells of bone marrow in rats was studied in cultures in vitro. Toxic effects of lead were manifested by a decrease in erythrocyte count and hemoglobin level in peripheral blood. Lead stimulated an increase in the number of fibroblasts, while the macrophage count dropped. The number of adipocytes remained unaffected.
Influence of Diethyldithiocarbamate on Nickel-Induced Hepatic Metallothionein in Rats
Authors: Khandelwal Shashi , Kachru Devendra N. , Tandon Sushil K.
Published: May 2017

The influence of sodium diethyldithiocarbamate (DDC) on 63nickel chloride-induced metallothionein (MT) and alterations in essential metal levels in the liver of rats was investigated. The induction of MT, Zn and Cu levels of the hepatic cytosolic “heat stable fraction” (HSF) by DDC increased with time up to 24 hr. Although MT, Zn and Cu were significantly greater at 17 hr than those at 6.5 hr after 63Ni administration, the Ni level decreased. The treatment with DDC at 6 hr, but not at 10 min, prior to 63Ni administration increased significantly the MT, Zn and Cu contents 17 hr after 63Ni administration over that caused by 63Ni alone at 17 hr., showing a synergistic effect. The induction of hepatic MT by 63Ni or DDC alone was prevented by cycloheximide but not by actinomycin D and seemed to be regulated at the protein synthesis level.
Toxicity of Mixtures of Trichloroethylene, Tetrachloroethylene and 1,1,1-Trichloroethane: Similarity of in Vitro to in Vivo Responses
Authors: Stacey Neill H.
Published: May 2017

The toxicities of various combinations of trichloroethylene (TRI), tetrachloroethylene (TET) and 1,1,1-trichloroethane (TCE) were examined in suspensions of rat hepatocytes and in vivo. For each pair and for the three solvents together, an interactive toxicity was demonstrated in vitro, as determined by release of potassium ion and cytoplasmic enzymes. A similar pattern of response was found after administration to the intact rat for increases in plasma alanine aminotransferase and sorbitol dehydrogenase, both indices of hepatotoxicity. Plasma urea levels were significantly elevated on exposure to the three chemicals together. Thus a remarkably similar pattern of toxicity was found in vitro and in vivo, which supports the possible use of hepatocyte suspensions as a screening procedure for toxicity of mixtures.
Effects of Inhaled Hexachlorobenzene Aerosols on Rat Pulmonary Host Defenses
Authors: Sherwood Robert L. , Thomas Peter T. , O'shea William J. , Bradof Jeannie N. , Ratajczak Helen V. , Graham Judith A. , Aranyi Catherine
Published: May 2017

Pulmonary bactericidal activity, macrophage phagocytic activity, alveolar macrophage (AM) enzyme activity, and T- and B-cell mitogenesis of lymphocytes from lung associated lymph nodes (LALN) or mesenteric lymph nodes (MESLN) were assessed in Sprague-Dawley rats exposed 4 hr/d, 4 days/wk for 1, 4, or 16 days to hexachlorobenzene (HCB) aerosols. Pulmonary bactericidal activity was depressed after 1 or 4 but not 16 exposures to 35 mg/m3 of HCB. AM phagocytosis of 51Cr-RBC in vitro was increased after 4 but not 1 or 16 exposures to HCB, and no effect was observed in peritoneal macrophages. HCB significantly enhanced mitogenesis in MESLN to the B-cell mitogen Salmonella typhimurium lipopolysaccharide (STM) after 4 exposures; LALN STM mitogenesis and LALN and MESLN mitogenesis to phytohemagglutinin (PHA) were not affected. After 16 exposures, however, the PHA responses in LALN and MESLN were significantly increased and decreased, respectively.
Dominant Lethal Assay of 2,4-Pentanedione Vapor in Fischer 344 Rats
Authors: Tyl Rochelle W. , Ballantyne Bryan , Fisher Louan C. , Tarasi Denise J. , Dodd Darol E.
Published: May 2017

2,4-Pentanedione (2,4-PD: CAS No. 123-54-6) is a volatile industrial chemical of moderate acute toxicity, centrally neurotoxic by repeated exposure to high vapor concentrations, fetotoxic, and clastogenic. Its wide use and known toxicology indicated the conduct of a dominant lethal assay. Male Fischer 344 rats, 20 per group, were exposed to 2,4-PD vapor concentrations (mean ± SD) of 0, 99.1 ± 2.2, 412 ± 12.6 and 694 ± 9.1 ppm, for 6 hr/day for 5 consecutive days. The day following the final exposure they were bred to unexposed female Fischer 344 rats, 2 per week for 8 consecutive weeks. Weight loss occurred with males during 2,4-PD exposure for the 412 and 694 ppm groups, with compensatory increased weight at 694 ppm, for the first two weeks postexposure. No histopathological change was seen in brain, testes or thymus from high concentration males sacrificed after eight weeks of mating. Minor transient reproductive and gestational effects were present at 412 and 694 ppm. At week 2 there was a reduction, not statistically significant, in the number of corpora lutea and total and viable implants per dam at 694 ppm, and a slight increase in preimplantation loss. At week 3 the number of pregnant females was slightly reduced at 412 and 694 ppm, causing a lowered female fertility index. At week 4 there was a slight reduction in the number of total and viable implants per litter and a significant preimplantation loss at 694 ppm. The dominant lethal factor (FL%) was increased slightly at 694 ppm for weeks 2 and 4. Thus, the “no observable effect” level for dominant lethal effects was 99 ppm. The results, although not statistically significant, are dose-related and compatible with a transient slight dominant lethal effect at the spermatid stage of spermatogenesis.
Some Scientific Judgments in the Assessment of the Risk of Environmental Contaminants
Authors: Cothern C. Richard
Published: May 2017

The assessment of risk due to environmental contaminants depends, in part, on scientific data. When such data are incomplete, as is usually the case, assumptions based on scientific judgments are made to analyze the consequences. Specifically, when health related data needed to assess the risk posed by environmental contaminants are missing or incomplete, it becomes necessary to make assumptions using scientific judgment to estimate the risk. Different scientists can and do make different assumptions, and the resulting differences in opinion can result in controversy. The present discussion presents a few of the consensus judgments of the Science Advisory Board (SAB) of the U. S. Environmental Protection Agency concerning the health effects and risk for such environmental contaminants as 1,2-dichloroethylene, dichloromethane, para-dichlorobenzene, polychlorinated biphenyls, perchloroethylene, and xylene, as well as the implications of the more likely cancer mechanisms, the exposure routes, and pharmacokinetics to the risk assessment process. In some of these examples, the scientific data have been developed to the extent that specific judgments by groups such as the SAB can result in greater confidence that one is correct in the assessment of risk. Because of the uncertainties in current scientific knowledge for many environmental contaminants, judgments differ and there is no right or wrong opinion.
Tropospheric Ozone: The Dynamics of Human Exposure
Authors: Lioy Paul J., , Dyba Raymond V.,
Published: May 2017

The conditions in the ambient atmosphere conducive to ozone exposure are examined, and placed into a context of the time arid locations where individuals would be expected to be affected by high ozone. This is done for both 1 h and 8 h averaging times. Concentrations of ozone in the ambient atmosphere can violate the National Ambient Air Quality Standard (NAAQS) and also the Time Weighted Average-Threshold Limit Value (TWA-TLV) for workers. Exposures that occurred in a 1982 episode associated with a health effects study are described in detail. The effective dose received by a camper at a children's summer camp appeared to be similar to that delivered to volunteers during a controlled human exposure study in which effects on pulmonary function were observed.
Developmental Toxicity of Clarified Slurry Oil Applied Dermally to Rats
Authors: Feuston Maureen H. , Kerstetter Stacy L. , Singer Edward J. , Mehlman Myron A.
Published: May 2017

Clarified Slurry Oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 pregnant rats at doses of 0, 4, 8, 30, 125, and 250 mg/kg I day. All groups received the test material on gestation days 0–19. CSO was applied undiluted and left uncovered on the skin; collars were placed on the rats to minimize ingestion of the test material. Signs of maternal toxicity, some of which were seen at dose levels as low as 8 mg/kg/day, included vaginal bleeding, decreased body weight gain, reduced food consumption, death, increased relative liver weights, atrophy of the thymus, and aberrant serum chemistry. The number of fetal resorptions / deaths was markedly increased and the number of viable offspring decreased by CSO at dosages of 30 mg/kg/day and above. The group receiving 250 mg/kg/day carried no viable offspring. Fetuses from pregnant females exposed to CSO at dose levels in excess of 8 mg/kg/day were smaller than those from control and 4 mg/kg/day groups, and their skeletons showed decreased ossification. Abnormal external development and visceral development were observed in living and dead fetuses exposed in utero to CSO at dose levels as low as 8 mg/kg/day. Based on these data, 4 mg/kg/day represents the No-Observed-Adverse-Effect-Level for both maternal and developmental toxicity.
Study of the Teratogenic Potential of Fd&C Red no. 40 When Given in Drinking Water
Authors: Collins Thomas F.X. , Black Thomas N. , Welsh John J. , Brown Lois H.
Published: May 2017

FD&C Red No. 40 in the drinking water at a level of 0, 0.2, 0.4, or 0.7% was available ad libitum to female Osborne-Mendel rats throughout gestation. The treated females consumed 273.6, 545.7, and 939.3 mg FD&C Red No. 40 per kg body weight per day, respectively, for the three dose levels. The animals were sacrificed on gestation day 20. No fetal terata were seen. There were no dose-related changes in maternal findings, number offetuses, fetal viability, or external or visceral variations. Skeletal development appeared similar to that of the control animals with the exception of the incidence of fetuses with reduced ossification of the hyoid, which was increased significantly at the 0.7% dose level. A dose-related increase occurred in the number of litters containing fetuses with at least two skeletal variations, but the numbers of litters with fetuses with at least one and at least three variations were not different from control values.
The Effects of Chronic Treatment and Withdrawal of Cns Depressants on Aggressive Behavior
Authors: Yen-Koo Helen C. , Tocus E.C. , Balazs T.
Published: May 2017

Young adult CD-I male mice were housed in individual cages throughout the study. Groups of 10 to 20 mice were given gradually increasing doses of delta-9-tetrahydrocannabinol (THC) at 6.25 to 25 mg/kg i.p., trifluoperazine (TFP) at 6 to 12 mg/kgp.o., phenobarbital sodium (PS) at 20 to 35 mg/kg p.o., morphine sulfate (MS) at 5 to 20 mg/kg i.p., methaqualone (MQ) 10 to 20 mg/kg p.o. or chlordiazepoxide (CDP) 10 to 25 mg/kg p.o. over four to six weeks to develop tolerance of these drugs. Following the development of tolerance, the drugs were withdrawn. On the fourth day of withdrawal, a young (3-4 weeks old) male mouse was introduced into the cage. When the intensity of the attack was measured by the percentage of animals that killed the intruder within four hours. The results indicated 0 to 4 percent in the controls, 50-54 percent for THC, 50 percent for TFP, 42 percent for PS and 57 percent for MS. In contrast, no killing behavior was exhibited by these mice after treatment with MQ or CDP. These data suggest that enhanced aggressive behavior, elicited by withdrawal from certain psychotropic drugs, may be measured by the killing (muricidal) behavior of isolated mice.
Protein Binding of Benzene under Ambient Exposure Conditions
Authors: Travis Curtis C. , Bowers John C.
Published: May 2017

Based on examination of exposure monitoring studies, we speculate that under ambient conditions benzene binds appreciably to plasma proteins. The binding capacity, n*[β], is estimated to be on the order of 10-9x M (90.0 ng/L) and the association constant, Kas, on the order of 2 × 1010 M-1 (.3 L/ng). These values indicate that protein binding of benzene is characterized by a very small capacity with a very large affinity. We predict that steady-state exposure to ambient benzene air concentrations in the range of 10 ppb to 1 ppb will result in 35 to 80 percent of benzene in blood being bound to plasma proteins.
Fetal Effects of Inhalation Exposure to Cyclohexanone Vapor in Pregnant Rats
Authors: Samimi Behzad S. , Harris Stephen B. , De Peyster Ann
Published: May 2017

Cyclohexanone (CH), a solvent and thinner that has extensive use in industry, was investigated for developmental effects using pregnant Sprague-Dawley rats exposed to 100, 250 or 500 ppm concentrations in an inhalation chamber for seven hours per day from days 5 through 20 of pregnancy. Controls were exposed to room air. Maternal weight gain at 250 and 500 ppm CH was only slightly lower than in the control dams, and a grey mottling of the lungs was seen in a few of the CH-exposed dams. There were no significant differences between the CH and control groups in fetal weight, resorption sites, fetal death or sex ratio. External and soft tissue examinations revealed no significant incidence of malformations or variations in CH-exposed animals. A slight increase in the mean percent of rudimentary ribs per litter was observed in the 250 and 500 ppm CH-exposed groups. However, no significant numbers of skeletal malformations were noticed in either the CH or room air control groups. It was concluded that respiratory exposure of rats to as much as 500 ppm CH during organogenesis was unlikely to be developmentally toxic.