Chair Restraint Research Articles

Effect of Fipronil Exposure on Hematological Aspects of Rhesus Monkeys (Macaca mulatta): Risk and Toxicity Assessment in Agro-Workers.

Fipronil (FPN) is a broad-spectrum phenylpyrazole insecticide, widely used in agriculture and veterinary medicine. Published research on FPN toxicity has established the fact that its inhalation or dermal exposure may lead to very serious clinical outcomes in non-target animals. In line to its exposure and toxicity related damage, FPN has been investigated in many invertebrates, however, its exposure-related noxiousness is less reported in higher animals. To assess the FPN-induced effects to agro-workers in the field, in the present study, we used physiological human surrogates, adult rhesus monkeys as models. We exposed well habituated, chair restraint adult rhesus monkeys with a field spray concentration of FPN (0.3 mg/1 mL distilled water) through an inhalation route in the closed system. Animals were divided into control and treatment groups, each containing three animals. Inflammatory and hematological effects were determined by evaluating the kidney and liver biomarker enzymes; serum creatinine and alanine transaminase (ALT), aspartate transaminase (AST) levels respectively. Our findings reveal that FPN treated monkeys show significantly increased levels of ALT (p = 0.000461), AST (p = 0.0681) and creatinine (p = 0.00656) as compared to the control group. Furthermore, significant differences of red blood cells (RBCs) (p = 0.0139) and white blood cells (WBCs) (p = 0.00642) were also observed in the treated and control group monkeys which reflect strong toxic effects on the blood cells. Our findings demonstrate that FPN exposure is very toxic to higher animals and causes severe damage to the liver and kidneys along with other clinical problems. The study highlights the effect and impact of passive inhalation of insecticides in intentionally carefree agro-workers and raises the concern of public awareness toward pesticides use.

Physical Restraint Use in Nursing Homes-Regional Variances and Ethical Considerations: A Scoping Review of Empirical Studies.

Physical restraints are known to violate human rights, yet their use persists in long-term care facilities. This study aimed to explore the prevalence, methods, and interventions related to physical restraint use among the elderly in nursing homes. The method described by Joanna Briggs was followed to conduct a scoping review without a quality assessment of the selected studies. An electronic search was conducted to find eligible empirical articles using MEDLINE, PsycINFO, EMBASE, Web of Science, Scopus, Google Scholar, CINAHL, and grey literature. The database search was performed using EndNote software (version X9, Clarivate Analytics), and the data were imported into Excel for analysis. The prevalence of physical restraint use was found to be highest in Spain (84.9%) and lowest in the USA (1.9%). The most common device reported was bed rails, with the highest prevalence in Singapore (98%) and the lowest (4.7%) in Germany, followed by chair restraint (57%). The largest number of studies reported the prevention and/or risk of falls to be the main reason for using physical restraints, followed by behavioral problems such as wandering, verbal or physical agitation, and cognitive impairment. Most studies reported guideline- and/or theory-based multicomponent interventions consisting of the training and education of nursing home staff. This review provides valuable insights into the use of physical restraints among elderly residents in nursing homes. Despite efforts to minimize their use, physical restraints continue to be employed, particularly with elderly individuals who have cognitive impairments. Patient-related factors such as wandering, agitation, and cognitive impairment were identified as the second most common reasons for using physical restraints in this population. To address this issue, it is crucial to enhance the skills of nursing home staff, especially nurses, in providing safe and ethical care for elderly residents with cognitive and functional impairments, aggressive behaviors, and fall risks.

Year one review: Staff perception on the implementation of the chair restraint on an adolescent psychiatric inpatient unit.

The purpose of this project was to assess perceptions, thoughts, and feelings of psychiatric mental health nursing staff when utilizing the chair restraint on an adolescent unit. Furthermore, to explore decision making related to choosing the chair restraint verses choosing to use the six-point board as a safety management intervention. This was a phenomenological qualitative study, utilizing semistructured interviews to explore the experiences of nursing staff, consisting of behavioral health specialists, and direct-care staff nurses who work on an adolescent psychiatric unit utilizing both chair restraint and the six-point board. Ten nursing staff were interviewed. Using thematic analysis, staff perceptions, thoughts, and feelings when using mechanical restraints for safety management were explored. Demographics were collected however, there was no variability in the responses and saturation was reached. Five themes emerged from the interviews. The Five themes that emerged were: Restraint chair was less traumatic and preferred, feelings of defeat when de-escalation was not successful, pushing away emotions as protection, units were short staffed, and patient behaviors were seen as a potential barrier to eliminating the six-point board. The results of this study will be used to guide to further develop behavioral health education, orientation for new staff, and to understand ways to support staff through their experiences in managing a patient's unsafe behaviors.

Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke.

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

Methods for chair restraint and training of the common marmoset on oculomotor tasks.

The oculomotor system is the most thoroughly understood sensorimotor system in the brain, due in large part to electrophysiological studies carried out in macaque monkeys trained to perform oculomotor tasks. A disadvantage of the macaque model is that many cortical oculomotor areas of interest lie within sulci, making high-density array and laminar recordings impractical. Many techniques of molecular biology developed in rodents, such as optogenetic manipulation of neuronal subtypes, are also limited in this species. The common marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to frontoparietal oculomotor areas, and may bridge the gap between systems neuroscience in macaques and molecular techniques. Techniques for restraint, training, and neural recording in these animals have been well developed in auditory neuroscience. Those for oculomotor neuroscience, however, remain at a relatively early stage. In this article we provide details of a custom-designed restraint chair for marmosets, a combination head restraint/recording chamber allowing access to cortical oculomotor areas and providing stability suitable for eye movement and neural recordings, as well as a training protocol for oculomotor tasks. We additionally report the results of a psychophysical study in marmosets trained to perform a saccade task using these methods, showing that, as in rhesus and humans, marmosets exhibit a "gap effect," a decrease in reaction time when the fixation stimulus is removed before the onset of a visual saccade target. These results are the first evidence of this effect in marmosets and support the common marmoset model for neurophysiological investigations of oculomotor control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in behaving primates has provided a wealth of information regarding the neural circuits underlying the control of eye movements. Such studies require restraint of the animal within a primate chair, head fixation, methods of acclimating the animals to this restraint, and the use of operant conditioning methods for training on oculomotor tasks. In contrast to the macaque model, relatively few studies have reported in detail methods for use in the common marmoset. In this report we detail custom-designed equipment and methods by which we have used to successfully train head-restrained marmosets to perform basic oculomotor tasks.

Assessment of Cardiac Troponin I Responses in Nonhuman Primates during Restraint, Blood Collection, and Dosing in Preclinical Safety Studies.

Limited information has been published on the use of cardiac troponin I (cTnI) as a biomarker of cardiac injury in monkeys. The purpose of these studies was to characterize the cTnI response seen in cynomolgus macaques during routine dosing and blood collection procedures typically used in preclinical safety studies and to better understand the pathogenesis of this response. We measured cTnI using two different methods, the Siemens Immulite cTnI assay and the more sensitive Siemens Troponin I-Ultra assay. We were able to demonstrate that after oral, subcutaneous, or intravenous dosing of common vehicles, as well as serial chair restraint for venipuncture blood collection, that minimal to mild transient increases in cTnI could be detected in monkeys with both assays. cTnI values typically peaked at 2, 3, 4, or 6 hr after sham dosing and returned to baseline at 22 or 24 hr. In addition, marked increases in heart rate (HR) and blood pressure (BP) occurred in monkeys during the restraint procedures, which likely initiated the cTnI release in these animals. Monkeys that were very well acclimated to the chairing procedures and had vascular access ports for blood sampling did not have marked increases in HRs and BP or increases in cTnI.

Design and validation of a child seat pretensor device

MAPFRE foundation and others have reported that every year around 6,500 children in Latin America in traffic accidents result in death [1]. The accident data related to infant deaths that do not carry a child restraint system that offers the protection levels as evidenced by the current safety devices are alarming. Although current child restraints systems have a good level of protection it is possible to design others that improve the performance of the current ones, being the improvement of child safety the main motivation for this study. This study is divided into two phases: the first one corresponds to the design of a pretensioner prototype which is attached to a baby chair holder and the second stage shows the operation of this device with simulated crash tests in vehicle forward facing direction. In the experimental phase is found that this device is able to decrease the forward excursion of the head, the neck efforts supported, the head and chest acceleration levels during a collision. Moreover, the results show the increased levels of protection offered to children, as well as the improved retention capacity for a chair restraint system equipped with the pretensioner developed in this work.

Efficient Cooperative Restraint Training With Rhesus Macaques

It is sometimes necessary for nonhuman primates to be restrained during biomedical and psychosocial research. Such restraint is often accomplished using a “primate chair.” This article details a method for training adult rhesus macaques to cooperate with a chair restraint procedure using positive and negative reinforcement. Successful training was accomplished rapidly in approximately 14 training days. The success of this training technique suggests that this method represents a refinement to traditional techniques. Further, this method worked effectively for animals previously deemed unfit for traditional pole-and-collar training.

Prevalence and Correlates of Urinary Incontinence in a Large Cohort of Psychiatric Inpatients

Urinary incontinence is physically and psychologically disabling, and little information exists about this condition in psychiatric populations. This exploratory study examined the prevalence of urinary incontinence and factors associated with this condition among persons with mental illness in three age groups: under 45, 45-64, and 65 and older. Data were from the Resident Assessment Instrument-Mental Health. Population-level data on adult inpatient psychiatric admissions (N=41,004) in Ontario, Canada, between October 2005 and June 2007 were analyzed. The prevalence of urinary incontinence was 6.2%, with higher rates among women and with increasing age. Across age groups, common treatable factors were found, including diarrhea, poorer cognitive and physical functioning, and use of chair restraint. Urinary incontinence was relatively common among psychiatric inpatients and associated with a number of treatable conditions. When it is assessed early during an admission and appropriate treatment measures are implemented, time in the hospital may decrease.

Acute and chronic stress increase DHEAS concentrations in rhesus monkeys

Most studies on the stress-responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis have focused on glucocorticoids, while few studies have investigated the adrenal secretion of dehydroepiandrosterone sulfate (DHEAS), which is unique to primates. Monkeys were chair-restrained for 2h per day for seven consecutive days, and blood samples were collected upon placement in the chair, and at 15, 30, 60 and 120 min later. Like cortisol, DHEAS concentrations increased throughout the initial session of chair restraint (acute stress). Unlike the cortisol response, which decreased after repeated exposure to the stressor, the DHEAS response was sustained throughout the seventh session of restraint (chronic stress) and response to the seventh session of restraint did not differ from the DHEAS response to the initial session. Like cortisol, DHEAS concentrations showed a diurnal rhythm with higher concentrations in the morning compared to the evening and a decrease in response to dexamethasone (DEX) administration. After repeated exposure to the stressor, the suppression of DHEAS in response to dexamethasone was more complete, suggesting an increase in negative feedback sensitivity. These data show that DHEAS concentrations increase in response to both acute and chronic (repeated) stress and provide another measure of HPA activity that parallels cortisol during acute responses to stress but diverges in chronic or repeated stress.

Novel restraint system for neuroendocrine studies of socially living common marmoset monkeys.

We describe a novel soft jacket and sling-harness restraint that permits species-typical postures for small-bodied primates, such as the common marmoset (Callithrix jacchus), during long-term (>6 h), continuous restraint. The restraint system is straightforward to use and manipulate, it is easily repaired, and the materials used are readily available. The soft jacket allows for increased versatility and longevity, and the sling-harness provides for greater movement and much longer duration of continuous restraint (up to 3 days) compared to a previously described, more conventional chair restraint for small-bodied primates. The new restraint system prevents the normal diurnal decrease in plasma cortisol levels across the daylight hours; however, it does not disrupt ovulatory cycles. Unlike the previously available techniques, therefore, this new restraint system is applicable to many neurobiological and neuroendocrine studies involving small-bodied, non-human primates and is especially suited to investigations requiring the maintenance of relationships within social groups.

Behavioral and physiological adaptation to repeated chair restraint in rhesus macaques

Physical restraint is a commonly used procedure when working closely with nonhuman primates. Nonhuman primates show rapid behavioral changes when learning the restraint procedure, and these changes have been taken to reflect behavioral and physiological habituation to the procedure. This study examined the behavioral and adrenocortical responses to repeated physical restraint in a large sample of adult male rhesus monkeys. Subjects showed a decline in behavioral agitation and cortisol concentrations across seven consecutive days of restraint. The changes in adrenocortical responsiveness were also coincident with an increased sensitivity to dexamethasone and a change in early morning basal cortisol secretion. The subjects were restrained for a single session 6 months later, and while the reduction in behavioral agitation was still present, the majority of changes in adrenocortical responsiveness were no longer present. These data show that behavior is not necessarily an indicator of underlying physiological processes and that the reduction of hypothalamic–pituitary–adrenal (HPA) activity with repeated restraint is due to physiological adaptation to high glucocorticoid concentrations and not to psychological habituation to the restraint procedures.

Effects of chair restraint on the strength of the tibia in rhesus monkeys.

To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post-mortem (r2 = 0.95, P < 0.0001). Inter-test precision was 4.28+/-1.4%. Normative data in 24 monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/-1.6 Nm2, P < 0.05). Five monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2-week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.

Steroid resistance in the squirrel monkey: an old subject revisited.

I t has been more than 30 yr since Brown et al. (1968) reported at the 52nd Annual FASEB Meeting in Atlantic City that squirrel monkeys have high circulating levels of the adrenal steroid cortisol compared with humans. This work was subsequently published in full (Brown et al. 1970) and confirmed by other laboratories (for example, Chrousos et al. 1982; Coe et al. 1978; Klosterman et al. 1986; Manogue et al. 1975). In the meantime, it was recognized that other steroid hormones, including progesterone, 17|3-estradiol, and testosterone, are also elevated in squirrel monkeys (Mendoza et al. 1978; Wilson et al. 1978; Wolf et al. 1977). Since these discoveries, a number of reports have contributed to our understanding of these phenomena, although not until recently have we begun to appreciate the molecular changes that led to these elevated hormone levels. The goal of this article is not to review our current knowledge of secretion and metabolism of each of these steroids in the squirrel monkey. Such review has been expertly achieved in chapters published in a volume of Advances in Experimental Medicine and Biology dedicated to the late Dr. Mortimer Lipsett (Chrousos et al. 1986a,b; Siiteri 1986). Rather, this article details recent findings that have provided insight into the molecular events that led to hypercortisolemia, briefly describing their relevance to the secretion of other steroid hormones in squirrel monkeys. The issue of elevated steroid hormone levels is important to laboratory animal science for several reasons. First, it should be appreciated that high circulating levels of some steroid hormones are a normal finding in captive squirrel monkeys. Second, it is generally agreed that this phenomenon has occurred as a normal physiological response to a state of hormone insensitivity or resistance in responsive tissues, including tissues such as the hypothalamus and pituitary gland, which mediate the feedback response. As a consequence, hormone levels are high to compensate for endorgan resistance, and squirrel monkeys enjoy a relatively normal pituitary-adrenal physiology albeit at a higher hormonal set-point. Thus, cortisol secretion in squirrel monkeys is appropriately stimulated by chair restraint (Brown et al. 1970) and social and environmental perturbations (Coe et

The Wisdom of the Body Revisited.

Being selected a Cannon lecturer by the American Physiological Society is a singular honor under any circumstances, but a particularly poignant one for me because of my origins in Cannon’s old Department at the Harvard Medical School. In fact, when I began my career there as an instructor 45 years

Pasteurella multocida infections in baboons (Papio cynocephalus)

The respiratory pathogenPasteurella multocida was isolated from infections of the laryngeal air sacs of two baboons and from abscesses in the neck or femoral area of two other baboons. The infections were associated with surgical procedures involving the cervical area, chronic catheterization, and chair restraint. The organism was also detected among the commensal pharyngeal flora in 2 of 15 clinically healthy, wildborn adult baboons. These findings suggest that the organism is harbored naturally in baboons and that exudative infections can occur secondary to specific procedures.

Hypoglycemic ‘Stress’ and Gonadotropin-Releasing Hormone Pulse Generator Activity in the Rhesus Monkey: Role of the Ovary

Observations of long standing have suggested that the 'stress' of chair restraint inhibits the GnRH pulse generator in normal female monkeys while this phenomenon is rarely observed in ovariectomized animals. The role of the ovary in the response of the GnRH pulse generator to the stress of insulin hypoglycemia was investigated in both intact and ovariectomized rhesus monkeys. Following an overnight fast the animals, previously habituated to restraint, were placed in primate chairs and GnRH pulse generator activity monitored electrophysiologically. Insulin-induced reductions in mean blood glucose concentrations of 10-40% of control values interrupted pulse generator activity in intact monkeys but were without effect in ovariectomized animals. With larger reductions in blood glucose, pulse generator activity was interrupted in both groups but the inhibition was twice as long in intact than in ovariectomized animals. The reduced responsiveness of ovariectomized animals to insulin hypoglycemia was significantly reversed by estradiol replacement. Naloxone administration did not prevent the hypoglycemia-induced inhibition of pulse generator activity in either intact or ovariectomized rhesus monkeys. It is concluded that hypoglycemic 'stress' inhibits the GnRH pulse generator by a nonopioidergic mechanism and that ovarian products, most probably estradiol, exacerbate this effect.

Restraint Inhibits Luteinizing Hormone and Testosterone Secretion in Intact Male Rhesus Macaques: Effects of Concurrent Naloxone Administration

The present study investigates how restraint affects the hypothalamo-hypophysial adreno-cortical axis and the hypothalamo-hypophysial gonadal axis in intact, adult male rhesus macaques. Restraint was chosen because it is not physically painful or harmful to the animal, but rather serves both as a physical and psychological stressor. Blood samples were collected from a remote site at 15-min intervals beginning at 07.00 h from tethered adult male rhesus macaques. Each of 4 animals was subjected to 6 h of chair restraint after a 3-hour control period in the animals' home cage. Samples were collected for an additional 6 h at the end of the restraint period when the animal was returned to its home cage. Brief anesthesia with ketamine (administered through the indwelling catheter) facilitated transfer of the animals to and from the chair. Blood samples were collected from 4 undisturbed males to document LH and testosterone secretion throughout the day. Plasma ACTH and cortisol, measured as indexes of stress, were elevated within 15 min after initiation of restraint and remained elevated for most of the restraint period. Conversely, LH and testosterone began to fall immediately after restraint and remained suppressed for several hours after the animals were removed from restraint and returned to their home cage. Testosterone levels were more consistently inhibited than were LH levels, a reflection of the fact that in some animals, testosterone remained low after the return of pulsatile LH secretion. In studies with naloxone (Nx), the opiate receptor antagonist (5 mg bolus plus 5 mg/h) was given beginning either at the initiation of restraint (n = 2) or 2 h thereafter (n = 2), and continued until the end of the restraint period. With Nx treatment of the restrained animals, both ACTH and cortisol were elevated as in the controls and LH and testosterone secretion were significantly increased within 1-2 h. However, after the Nx treatment was terminated and the animals were returned to their home cages, plasma levels of LH and testosterone were not different from levels in restrained animals and were significantly less than levels in untreated animals. These data show that restraint is a potent stimulus for activation of the HPAC axis and inhibits both LH and testosterone release. The pathway through which restraint inhibits LH release probably includes endogenous opiate suppression of hypothalamic GnRH release since Nx partially blocks the effect of stress.

The use of nonmetal electrodes in electroejaculation of restrained but unanesthetized macaques

A successful technique for electroejaculation with nonmetallic electrodes cut from defibrillation pads is described. Twenty-six adult male cynomolgus and eleven adult male rhesus macaques were electroejaculated while immobilized with chair restraint. From 123 attempted electroejaculations in both species of macaques, 119 semen specimens were obtained. The volume, concentration, % motility, and % normal forms of cynomolgus and rhesus macaque semen are presented. The use of nonmetallic electrodes provides a high quality ejaculate while minimizing the risks of adverse affects on valuable populations of macaques.

Changes in Basal and Stimulated Growth Hormone Secretion in the Aging Rhesus Monkey: A Comparison of Chair Restraint and Tether and Vest Sampling*

We studied basal serum GH and GH responses to iv clonidine and insulin-induced hypoglycemia in a group of four young (5-7 yr old) and four older (10-14 yr old) adult male rhesus monkeys under two restraint conditions, chair adaptation and a tether and vest system, to determine what changes in GH secretion occur with aging. The serum GH response to iv administration of GH-releasing hormone (GHRH) was also studied in the groups under tether and vest restraint. Serum samples were collected every 15 min and assayed for GH using a human GH RIA and for cortisol using an enzyme-linked immunosorbant assay. GH and cortisol concentrations in the young and older groups were analyzed with analysis of variance (ANOVA). In the chaired studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (2.7 +/- 0.8 vs. 3.5 +/- 0.5 micrograms/L; P = 0.0002). Prestimulation GH was lower before clonidine and insulin in the older chaired group (1.1 +/- 0.5 and 2.3 +/- 0.6 micrograms/L, respectively) compared to the younger group (3.6 +/- 0.8 and 3.8 +/- 0.7 micrograms/L, respectively; P less than 0.001). Poststimulation GH was lower after clonidine and insulin in the older chaired group (3.2 +/- 2.4 and 7.1 +/- 2.8 micrograms/L, respectively) compared to the younger chaired group (6.3 +/- 2.2 and 10.3 +/- 3.0 micrograms/L, respectively; P less than 0.05), but the differences in GH increments were not statistically significant. In the tether and vest studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (1.7 +/- 0.4 vs. 3.5 +/- 1.2 micrograms/L; P less than 0.0001). Prestimulation GH concentrations were also lower in the older tethered animals before clonidine (2.1 +/- 0.3 micrograms/L) and GHRH (1.4 +/- 0.2 micrograms/L) compared to levels in the younger animals (3.1 +/- 0.9 and 3.2 +/- 0.7 micrograms/L; P = 0.0023 and P = 0.0001, respectively). The younger tethered animals had greater poststimulation responses to clonidine (8.7 +/- 3.0 micrograms/L), insulin (8.8 +/- 3.6 micrograms/L), and GHRH (6.0 +/- 2.4 micrograms/L) than the older animals (3.8 +/- 0.9, 3.9 +/- 2.5, and 2.9 +/- 0.7 micrograms/L; P less than 0.0001, P = 0.0025, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)