The cost-benefit of genomic testing of heifers and using sexed semen in pasture-based dairy herds.

Recent improvements in dairy cow fertility and female reproductive technologies offer an opportunity to apply greater selection pressure to females. This means there may be greater incentive to obtain genomic breeding values for females. We modeled the impact of changes to key parameters on the net benefit from genomic testing of heifer calves with and without usage of sexed semen. This paper builds on earlier cost-benefit studies but uses parameters relevant to pasture-based systems. A deterministic model was used to evaluate the effect on net benefit due to changes in (1) reproduction rate, (2) genomic test costs, (3) availability of parent-derived breeding values (EBVPA), and (4) replacement rate. When the use of sexed semen was included, we also considered (1) the proportion of heifers and cows mated to sexed semen, (2) decreases in conception rate in inseminations with sexed semen, and (3) the marginal return for surplus heifers. Scenarios with lower replacement rates and no availability of EBVPA had the largest net benefits. Under current Australian parameters, the net benefit of genomic testing realized over the lifetime of genotyped heifers is expected to range from A$204 to A$1,124 per 100 cows for a herd with median reproductive performance. The cost of a genomic test, a perceived barrier to many farmers, had only a small effect on net benefit. Genomic testing alone was always more profitable than using sexed semen and genomic testing together if the only benefit considered was increased genetic gain in heifer replacements. When other benefits (i.e., the higher sale price of a surplus heifer compared with a male calf) were considered, there were combinations of parameters where net benefit from using sexed semen and genomic testing was higher than the equivalent scenario with genomic testing only. Using sexed semen alongside genomic testing is most likely to be profitable when (1) used in heifers, (2) the marginal return for selling surplus heifers (sale price minus rearing costs) is greater than A$400, and (3) conception rates of no more than 10 percentage points lower than those achieved using conventional semen can be realized. Net benefit was highly dependent on the marginal return. Demonstrating that the initial investment in genomic testing can be recouped within the lifetime of the heifers tested may assist in the development of extension messages to explain the value of genomic testing females at the herd level.

Nanoparticle catalysts for proton exchange membrane fuel cells: can surfactant effects be beneficial for electrocatalysis?

Platinum (Pt) nanoparticles were prepared in aqueous dispersion using the non-ionic surfactant nonylphenolethoxylate (NP9) and the cationic surfactant tetradecyltrimethylammonium bromide (TTAB). The surfactants were added to give colloidal stability. Such species are generally considered to block electrochemical active sites and to be undesirable for the oxygen reduction reaction (ORR). However, the procedures used to remove them are likely to cause particle aggregation. The purpose of this work was to investigate the effect of surfactants on Pt ORR performance. The nanoparticles prepared using NP9 showed good oxygen reduction performance when compared with the commercial Pt/C catalyst TKK, without removing the surfactant. In contrast, Pt nanoparticles prepared using the cationic surfactant TTAB showed very poor ORR performance, exemplifying the importance of careful surfactant selection in catalyst synthesis.

On-farm net benefit of genotyping candidate female replacement cattle and sheep.

The net benefit from investing in any technology is a function of the cost of implementation and the expected return in revenue. The objective of the present study was to quantify, using deterministic equations, the net monetary benefit from investing in genotyping of commercial females. Three case studies were presented reflecting dairy cows, beef cows and ewes based on Irish population parameters; sensitivity analyses were also performed. Parameters considered in the sensitivity analyses included the accuracy of genomic evaluations, replacement rate, proportion of female selection candidates retained as replacements, the cost of genotyping, the sire parentage error rate and the age of the female when it first gave birth. Results were presented as an annualised monetary net benefit over the lifetime of an individual, after discounting for the timing of expressions. In the base scenarios, the net benefit was greatest for dairy, followed by beef and then sheep. The net benefit improved as the reliability of the genomic evaluations improved and, in fact, a negative net benefit of genotyping was less frequent when the reliability of the genomic evaluations was high. The impact of a 10% point increase in genomic reliability was, however, greatest in sheep, followed by beef and then dairy. The net benefit of genotyping female selection candidates reduced as replacement rate increased. As genotyping costs increased, the net benefit reduced irrespective of the percentage of selection candidates kept, the replacement rate or even the population considered. Nonetheless, the association between the genotyping cost and the net benefit of genotyping differed by the percentage of selection candidates kept. Across all replacement rates evaluated, retaining 25% of the selection candidates resulted in the greatest net benefit when genotyping cost was low but the lowest net benefit when genotyping cost was high. Genotyping breakeven cost was non-linearly associated with the percentage of selection candidates retained, reaching a maximum when 50% of selection candidates were retained, irrespective of replacement rate, genomic reliability or the population. The genotyping breakeven cost was also non-linearly associated with replacement rate. The approaches outlined within provide the back-end framework for a decision support tool to quantify the net benefit of genotyping, once parameterised by the relevant population metrics.

The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance.

REASONS FOR PERFORMING STUDY: Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. HYPOTHESIS: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. METHODS: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sensitivity (IS) and pancreatic beta cell function while controlling for possible dietary and managemental influences on IR. RESULTS: Evidence of significantly improved IS and decreased pancreatic beta cell secretion was found following metformin treatment. The magnitude of effect was greater at earlier resampling (6-14 days) than at later times (23-220 days). Apparent subjective clinical benefits were good but less favourable than effects on IR. CONCLUSIONS: Metformin is safe and appears to increase IS in equids. POTENTIAL RELEVANCE: Metformin may be indicated as a treatment for IR in equids. Further studies are required to define appropriate selection of subjects warranting therapy, dosing schedule and pharmacokinetics.

Psychophysiological correlates of posttraumatic stress disorder in Vietnam veterans.

We measured event-related brain potential (ERP) component amplitudes and heart rate (HR) to four intensities of randomly presented tones in two matched groups of drug-free male Vietnam veterans: 12 patients diagnosed with posttraumatic stress disorder (PTSD) and 6 normal combat veterans. Subjects were evaluated with structured diagnostic interviews and anxiety and depression rating scales. We found a significant group X intensity interaction for P2 peak amplitude at CZ. Subjects were classified as augmenters or reducers: positive P2 slopes as a function of stimulus intensity implying augmentation and negative slopes implying reduction. Nine of 12 PTSD subjects were reducers (sensitivity of 75%) and 5 of 6 normals were augmenters (specificity of 83.3%). By the third and fourth second following tone onset, the mean HR of PTSD subjects increased more than twice that of the normals. HR change scores were significantly responsive to the manipulation of stimulus intensity and to the difference between our two groups. P2 reduction differentiates Vietnam veterans with combat-related PTSD from combat veteran controls, and PTSD subjects are more autonomically arousable than their combat veteran peers.

HLA antigens in tardive dyskinesia.

Fifty-three male, Caucasian, neuroleptic-treated patients with chronic schizophrenia were examined for the presence of tardive dyskinesia (TD) and were tissue typed. The group with TD (n = 25) was compared to the group without TD (n = 28). HLA-DR4 was more prevalent in the group with TD than in the group without TD, with a relative risk of 3.04 for TD with HLA-DR4 present, although this finding is not statistically significant when corrected for the number of nonparametric comparisons. Other investigations reported an association between HLA-B44 and TD, or between HLA-B44 and neuroleptic-induced parkinsonism. Potential explanations relating the findings of these investigations are discussed.

Drug holidays and serum haloperidol levels in schizophrenic patients.

Chronic hospitalized schizophrenic patients receiving haloperidol were placed on drug holidays for 2 days. Serum haloperidol levels in these patients decreased to about 60% of the levels seen just prior to the usual morning dosing during the drug holiday. Control subjects not given a drug holiday showed stable day-to-day serum haloperidol levels. The small drop in serum haloperidol blood levels may relate to the lack of relapse observed in such patients.

Effects of repeated drug holidays on serum haloperidol concentrations, psychiatric symptoms, and movement disorders in schizophrenic patients.

In a crossover experiment the authors investigated the effects of repeated weekly, 2-day, haloperidol drug holidays on serum haloperidol concentrations, mental status, and neuroleptic-induced movement disorders in seven chronic schizophrenic patients. Haloperidol concentrations decreased about 64% during the initial 36 hours of drug holiday and subsequently increased slightly during the next 24 hours of drug holiday. Two-day weekly drug holidays for 6 weeks resulted in an average reduction of 25% in serum haloperidol concentrations at all drug holiday points. Mental status and movement disorders scores, rated by observers blind to the drug-holiday condition, were not significantly affected by drug holidays.

Differential sensitivity to morphine in nervous and normal pointer dogs.

The effects of morphine and pentobarbital on body temperature and heart rate were studied in a line of pointer dogs characterized as genetically nervous. Intravenous administration of cumulative doses of morphine to the conscious, restrained, nervous dogs produced less tachycardia and hypothermia than were observed in control dogs. Nervous and control dogs did not differ in their responses to pentobarbital. These data are consistent with recent findings that nervous dogs have a lower density of opioid receptors in the brain than do control dogs.

Lithium visibility in rat brain and muscle in vivo by 7Li NMR imaging.

The apparent concentration of lithium (Li) in vivo was determined for several regions in the brain and muscle of rats by 7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determined in vitro by high-resolution 7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the 7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

In vivo 7Li nuclear magnetic resonance study of lithium pharmacokinetics and chemical shift imaging in psychiatric patients.

New data are presented on the application of 7Li in vivo nuclear magnetic resonance (NMR) spectroscopy to human studies. The technique was used to monitor the between-dose pharmacokinetics of lithium (Li) in brain for three patients on Li therapy. Brain Li concentrations were at their highest from 0 to 2 hours after the peak occurred in serum concentration. Elimination from brain tissue took longer than elimination from muscle, and no signal could be detected from brain at 10 days after termination of therapy. A birdcage radiofrequency coil for 7Li was constructed and used to measure the 7Li spin-lattice relaxation time of 4.6 seconds in vivo in human head, and to acquire preliminary spectroscopic images of a phantom and human brain.

Fluoxetine and trifluoperazine in human brain: a 19F-nuclear magnetic resonance spectroscopy study.

Fluorine-19 (19F) is a nonradioactive isotope that is well-suited to nuclear magnetic resonance spectroscopy (NMRS) and is a constituent of several medications used to treat psychiatric illnesses. Fluoxetine, a trifluorinated agent, generated a signal from brain that was readily measured by 19F-NMRS. Estimated brain concentrations ranged from 1.3-5.7 micrograms/ml in six subjects at a steady state dose of 40 mg/day. Enhanced sensitivity of 19F has been obtained by conforming the surface coil to the shape of the forehead. Hence, at the current state of development, 19F-NMRS can be applied to clinical questions relevant to concentrations of fluoxetine in brain. We also report observation of NMRS signals from fluorinated neuroleptics in a number of patients at steady state. These signals continue to be difficult to obtain, although a correlation between dose and estimated brain concentrations is suggested.

Serum haloperidol and neuroleptic receptor levels in chronic psychosis.

Serum haloperidol and serum dopamine blocking activity were measured, and steady state levels were compared in 22 chronic male schizophrenic patients. Haloperidol levels were measured by high pressure liquid chromatography (HPLC), and dopamine blocking activity was measured by a radioreceptor assay (NRRA). Clinical status was determined by the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Patients were stabilized on individual doses of haloperidol for at least three weeks and dosages ranged from five to 200 mg per day. All measures were determined on two occasions, one week apart. All measures (AIMS, BPRS, HPLC, and NRRA) showed a high degree of repeated test reliability. The behavioral measures showed a high degree of interobserver reliability on both occasions. There were significant correlations at both time points among haloperidol dosage, serum haloperidol levels, and dopamine blocking activity. Although the correlations between serum levels measured by HPLC and NRRA were positive and significant on both occasions, they never accounted for more than 58 percent (coefficient of variation) of the total variance.

EEG power spectra of dysphonetic and nondysphonetic poor readers.

Two subtypes of poor readers, dysphonetic and phonetic, were compared on EEG spectral values obtained as they viewed strings of letters and short words. Dysphonetic poor readers had significantly higher values than phonetics in the theta and delta bands. Both phonetic and dysphonetic poor readers had lower beta values than adequate reading children with Attention Deficit Disorder. This evidence indicates that poor readers, especially dysphonetics, were less actively engaged in the task.

Prevalence of post traumatic stress disorder and other psychiatric diagnoses in three groups of abused children (sexual, physical, and both).

OBJECTIVE: The purpose of this study was to compare the prevalence of Post Traumatic Stress Disorder and other diagnoses in three groups of abused children, sexual only (N = 127), physical only (N = 43), and BOTH (N = 34). METHOD: The children, aged 7 to 13 years, were referred to the project from several sources at Arkansas Children's Hospital and from associated local agencies. The victims and caregivers were separately administered the Diagnostic Interview for Children and Adolescents, Revised Version (DICA). Additionally, caregivers and classroom teachers completed the Child Behavior Checklist (CBCL). Characteristics of the abuse were obtained from an investigative questionnaire. RESULTS: Both victims and caregivers endorsed high rates of disorders, with caregivers generally giving higher rates than children and boys having more externalizing diagnoses than girls. Children in the BOTH group had more diagnoses overall. Concordance between victims and caregivers was modest. PTSD was significantly comorbid with most affective disorders. On the CBCL, caregivers rated girls less disturbed than boys and the sexually abused only group less disturbed than the other groups. Teachers rated the boys more adversely than girls but did not see differences by abuse group. A younger age of onset of sexual abuse and coercion to maintain secrecy predicted a higher number of total diagnoses. Also, children who were physically abused by males had more diagnoses than those physically abused by females. CONCLUSIONS: Children who have been both physically/sexually abused appear to be at highest risk of psychiatric disturbance. PTSD, though common (circa one-third of victims), is generally comorbid with other affective disorders.

The effect of different planes of nutrition before mating on the reproductive performance of Masham ewes.

A total of 69 ewes were fed either on a low nutritional plane for six weeks prior to mating and for four weeks postmating (LL), or on a low nutritional plane for three weeks and then on a high nutritional plane (LH), or on a high nutritional plane throughout (HH). Ewes at mating were 49.3, 63.7 and 70.6 kg liveweight respectively and their body condition scores were 1.6, 2.9 and 3.8. There was a significant difference in ovulation rate: LL = 1.53, LH = 2.13 and HH = 2.27, and in lambing per cent: 77, 150 and 186 respectively. Under the system of indoor feeding practised at mating, there was no economic advantage to be gained from flushing, but normally ewes would be flushed outside.

EEG power spectra of children with dyslexia, slow learners, and normally reading children with ADD during verbal processing.

EEG power spectra were studied in two poor reader groups (with dyslexia and slow learning) and a normally reading clinic control group (with attention deficit disorder) as the children viewed strings of words and letters (seven categories). The children ranged in age from 7.5 to 12 years; 33 were girls, 86 were boys. Bilateral temporal and parietal sites and four midline sites were used. The major difference between groups was in the low beta band, where the ADD group had greater power at the parietal and midline sites. Also, the slow learner group had marginally greater low beta at the left than right temporal site, with the opposite trend found for the dyslexic and ADD groups. Across groups, power was greater at the right than at the left parietal site in the delta and alpha bands and at the right than at the left temporal site in the low beta band. Stimulus category effects were modest, with some alpha suppression to word strings, relative to letter strings, found in the poor readers. In correlational analyses, the combination of greater low beta and less theta power significantly predicted better reading and spelling. Results indicate that the adequate readers more actively processed the stimuli than did the poor readers.

Coronary blood flow in dogs: effect of person.

Experiments on dogs with electromagnetic flow probes implanted around a coronary artery and the ascending aorta indicate that the entry of a person into the experimental chamber can cause a remarkable increase in coronary blood flow. Heart rate usually increases considerably, blood pressure increases only slightly, while aortic blood flow increases at variable times before and after coronary blood flow. It is not yet clear whether these cardiovascular effects are due purely to "effect of person" or to conditioning, with the person as the signal for the momentary coronary occlusion (which the person subsequently accomplishes by manually closing a snare).

Posttraumatic stress disorder: a sensitization reaction.

This article discusses past research bearing on the question of the etiology of Posttraumatic Stress Disorder (PTSD). It argues that PTSD can be adequately accounted for by a process of emotional sensitization and that this is a more parsimonious explanation than the two-factor learning theory of Mowrer, now postulated by several writers. In brief, the etiology and subsequent development of PTSD is viewed as the result of the sensitization of fear/anxiety which is linked to a variety of to be conditional stimuli by both backward and forward association: these become conditional stimuli (CSi) once paired with the instigating circumstances. It is furthermore assumed that PTSD will not occur in the absence of a genetic susceptibility that may vary from zero to absolute certainty. Thus far, our evidence is limited to a sensitivity to loud sounds, but it is highly probable that touch and other sensory systems are involved (not necessarily in parallel). The fact that abuse often leads to behavioral disorders, including sexually seductive behaviors in children sexually abused, requires a recognition that emotional reactions other than fear may be sensitized. Fear in combination with pleasure or pleasure alone coupled with a loss of self-esteem may explain these acting-out behaviors.

An event-related brain potential investigation of PTSD and PTSD symptoms in abused children.

We tested 186 children ranging in age from 6 years, 10 months to 13 years, 7 months; 174 suffered either physical and/or sexual abuse, and 12 were nonabused children. Abused subjects were grouped in four different ways. The primary grouping was based on whether subjects satisfied the DSM III-R criteria for posttraumatic stress disorder (PTSD). Secondary groupings were based upon the three symptom clusters used to make the PTSD diagnosis (arousal, avoidance, and reexperiencing). In each of these groupings three separate subgroups were formed with approximately 25 percent in the high and low symptom count subgroups and the remaining 50 percent in the middle symptom count subgroup. Subjects listened to four different intensity levels (65, 80, 95, and 102 dB) of a 1 KHz tone, pseudo-randomly ordered, while event-related brain potentials (ERPs) were recorded. Two separate blocks were used, one with short intervals (4 +/- 1 sec) between tones and the other with longer intervals (17 +/- 2 sec). PTSD subjects presented a greater P2-N2 ERP intensity gradient (i.e., a larger increase in the P2-N2 ERP component as tone intensity increased) than did abused subjects without PTSD. Abused subjects with the highest number of reexperiencing symptoms showed a similar P2-N2 augmenting effect when compared to those with the lowest number of reexperiencing symptoms. Subjects with the highest number of arousal symptoms showed a shallower intensity gradient for the N1-P2 ERP component than did those with fewer arousal symptoms. The results are discussed in relation to previous results reported on adults with PTSD and in terms of CNS processing of stimulus intensity information.