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 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.

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.

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.

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.

The distribution of lithium in rat brain and muscle in vivo by 7Li NMR imaging.

The regional distribution of lithium (Li) in vivo was determined on a relative basis in the brain and muscle of rats by 7Li NMR imaging. Both high resolution 7Li NMR spectroscopy and atomic absorption spectrophotometry were performed on extracts of brain and muscle tissue from the same rats. The average in vivo results were generally in good agreement with the corresponding average in vitro results, despite the relatively low signal-to-noise ratio of the in vivo images. There was good agreement between the two in vitro methods of analysis, both on average and for individual animals. Significant differences were found in vivo among Li concentration ratios for the various brain regions and muscle by 7Li imaging, as well as by the in vitro methods.

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.

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.

Internalizing and externalizing characteristics of sexually and/or physically abused children.

This study evaluates the behavioral consequences of childhood abuse (sexual, physical, or both), with particular focus on prevalence of posttraumatic stress disorder (PTSD). Three abuse type groups and nonabused controls were contrasted on behavioral rating scales and on structured psychiatric interview data. The participants (109 abused children and 16 normal control children) were recruited from Arkansas Children's Hospital and local agencies for abused children. As expected, proportionately more females than males were sexually abused. Overall, males were rated as more disturbed than females. Type of abuse did not consistently influence behavioral ratings. Externalizing scores were significantly higher than internalizing scores in all abused groups. PTSD was diagnosed in 50% of the abused children, with a higher rate for boys who had been sexually abused as opposed to physically abused only (58% versus 13%). The most frequent comorbid condition with PTSD was Separation Anxiety. Sexually abused boys were hospitalized for psychiatric treatment at a higher rate than were other abused children.

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.

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.

Anticardiolipin antibodies in a sample of chronic schizophrenics receiving neuroleptic therapy.

Drug-induced antiphospholipid antibodies have been considered insignificant, a belief that has recently been questioned. Previous studies noted an association between chlorpromazine treatment and the presence of anticardiolipin antibodies (ACA), especially IgM ACA, and have suggested that thrombosis might be more likely in the presence of IgG ACA. We studied the cases of 27 patients receiving long-term neuroleptic therapy who had no history of cerebrovascular disease. IgG ACA was present in 7 (26%) of the 27, and IgM ACA was present in 5 (19%), yet none had shown any manifestations of cerebrovascular disease since initiation of neuroleptic therapy. These data suggest that drug-induced ACA do not predispose to cerebrovascular disease, even when IgG ACA is predominant.

In vivo 19F spin relaxation and localized spectroscopy of fluoxetine in human brain.

Fluorine-19 NMR spectroscopy was used to monitor the anti-depressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo 19F spin-lattice relaxation time (T1) of fluoxetine for five patients by the inversion-recovery technique. The individual T1s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T1. The individual T1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo 19F resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active metabolite norfluoxetine, as demonstrated by the in vitro 19F NMR spectrum of the lipophilic extract of a small section of brain. In vitro quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 micrograms/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.

Visual slow brain potentials in children with attention deficit disorder.

Using a two-stimulus reaction time paradigm, with two separate reward conditions (contingent and noncontingent), we compared slow wave brain potentials (ERPs) in 144 children with attention deficit disorder (ADD) and 30 normal control children. This article reviews the findings during the 900 msec visual warning stimulus. As we had expected, based on ERP work of Forth and Hare (1989) and Raine, Venables and Williams (1990), and on previous work from our own laboratory, the group differences were found in the negative slow wave portions of the ERP complex during the contingent reward condition but not during the noncontingent condition. Aggressive hyperactive subjects with attention deficit disorder (ADDHA) were discriminated from nonaggressive subjects (including control subjects) during the contingent reward condition in the following ways: (1) greater fronto-central negativity (640-900 msec slow wave) and (2) greater right parietal than left parietal negativity (430-750 msec slow wave). All ADD subgroups, when compared to control (CONTR) subjects, showed greater slow wave negativity (700-900 msec) at the midline occipital electrode site during the contingent reward condition. This could be explained in part as an IQ effect on ERPs reflecting the IQ difference between the ADD subgroups and the controls. These slow wave findings seem to relate to attentional problems of these children. They are discussed in terms of a psychobiological model of inhibition/disinhibition and appetitive activation.

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).

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.

Inefficacy of propranolol in attenuation of drug-induced parkinsonian tremor.

We investigated the tremolytic effect of long-acting propranolol (propranolol-LA) in six subjects with drug-induced parkinsonism (DIP), using a double-blind, placebo-controlled, crossover experimental design. Subjects received propranolol-LA for 2 weeks and placebo for 2 weeks, with no change in neuroleptic treatment. Tremor frequency and amplitude were objectively quantified at the end of each 2-week period by computerized tremorgram recording. There were no significant differences in attenuation of DIP tremor by propranolol-LA and placebo. Previous investigations reported in the literature have found propranolol to attenuate the tremor of idiopathic parkinsonism (IPD). It is expected that DIP and IPD tremor would respond similarly to propranolol if a solely peripheral or spinal cord tremolytic action were operative. A possible differential attenuation of IPD tremor and DIP tremor provides support for the concept of a higher central tremolytic mechanism of beta-adrenergic receptor-blocking drugs.

Human brain fluoxetine concentrations.

Data on 22 subjects treated with fluoxetine suggest that magnetic resonance spectroscopy (MRS) of fluorine-19 can measure brain concentrations of fluoxetine/norfluoxetine in vivo. Fluoxetine accumulates in the human brain relative to plasma, with brain concentrations of fluoxetine/norfluoxetine ranging up to 10.7 micrograms/ml. Brain concentrations may reach a plateau between 6 and 8 months of treatment. The apparent concentration in brain relative to plasma is 20:1, roughly parallel to brain antidepressant concentration ratios in animal studies.