Neutron source reconstruction using a generalized expectation-maximization algorithm on one-dimensional neutron images from the Z facility.

Magnetized Liner Inertial Fusion experiments have been performed at the Z facility at Sandia National Laboratories. These experiments use deuterium fuel, which produces 2.45 MeV neutrons on reaching thermonuclear conditions. To study the spatial structure of neutron production, the one-dimensional imager of neutrons diagnostic was fielded to record axial resolved neutron images. In this diagnostic, neutrons passing through a rolled edge aperture form an image on a CR-39-based solid state nuclear track detector. Here, we present a modified generalized expectation-maximization algorithm to reconstruct an axial neutron emission profile of the stagnated fusion plasma. We validate the approach by comparing the reconstructed neutron emission profile to an x-ray emission profile provided by a time-integrated pinhole camera.

Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables.

Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.

An investigation into the suitability of a commercial real-time PCR assay to screen for Taylorella equigenitalis in routine prebreeding equine genital swabs.

REASONS FOR PERFORMING STUDY: Standard bacteriological methods for identifying Taylorella equigenitalis in cervical smears are time consuming. Therefore, a more rapid real-time PCR assay was evaluated for its suitability in screening swabs. OBJECTIVE: To compare the results of a commercially available real-time PCR assay with routine microbiological culture for the identification of T. equigenitalis, the causative organism of contagious equine metritis, in equine genital swab samples, under 'field trial' conditions. MATERIALS AND METHODS: Routine prebreeding genital swabs (n=2072) collected from Thoroughbred mares and stallions during 2009 were examined together with stored T. equigenitalis positive material. Swabs were cultured for T. equigenitalis using standard microbiological techniques. Bacterial lysates were isolated from the swabs and examined for the presence of a 16S DNA fragment of T. equigenitalis, using a commercial multiplex real-time PCR assay system. RESULTS: There was complete concordance between positive and negative results obtained by the 2 methods. Real-time PCR also detected T. equigenitalis DNA from swabs that were negative using standard microbiological culture after 6 months' storage at +4 degrees C but from which T. equigenitalis had been isolated following collection. The sensitivities of real-time PCR and bacterial culture were both 10(-3) (equivalent to 3 colony-forming units). CONCLUSION AND CLINICAL RELEVANCE: Routine bacterial culture of T. equigenitalis requires an incubation period of not less than 7 days before a conclusive negative result can be obtained, whereas bacterial extraction and real-time PCR assay can be completed in less than 6 h. The commercially-available PCR assay tested provided a rapid and reliable method for the identification of T. equigenitalis from equine genital swabs and could be usefully employed for the screening of mares and stallions for preseason Horserace Betting Levy Board (HBLB) Code of Practice and in other situations such as for bloodstock sales screening requirements, overcoming the current delays imposed by bacterial culture requirements. Its use could be quality assured by the existing HBLB biannual testing scheme for designated laboratories.

Serum cardiac troponin I concentrations in cattle with cardiac and noncardiac disorders.

BACKGROUND: Making a clinical diagnosis of pericarditis in cattle is difficult and additional diagnostic tests are needed to evaluate cattle with suspected pericarditis. Serum cardiac troponin I (cTnI) concentrations are increased in cattle with pericarditis, but the utility of measuring serum cTnI concentrations in cattle with suspected pericarditis in cattle remains unclear. OBJECTIVES: To determine if serum cTnI concentrations in cattle can be used to differentiate pericarditis from other cardiac disorders and noncardiac thoracic diseases. ANIMALS: Seventy-seven clinically diseased cattle and 19 healthy control cattle. METHODS: Serum cTnI concentrations were measured using an Immunlite Troponin I immunometric chemiluminescent assay in consecutive cases of postmortem-confirmed pericarditis (n=18), endocarditis (n=15), chronic suppurative pneumonia (n=13), congenital heart disease (n=10), reticulitis (n=3), mediastinal abscess (n=7), thymic lymphoma (n=6), and caudal vena cava thrombosis (n=5). Serum cTnI concentrations were measured in 19 healthy cattle. RESULTS: Although serum cTnI concentrations were significantly higher in cattle with pericarditis compared with healthy cattle, they were not significantly different from concentrations in cattle with endocarditis, congenital cardiac disease, mediastinal abscess, reticulitis, caudal vena cava thrombosis, or chronic suppurative pneumonia. CONCLUSIONS: Serum cTnI cannot be used to distinguish cattle with pericarditis from cattle with other primary cardiac diseases. In addition, serum cTnI concentrations cannot distinguish between cattle with primary cardiac diseases and those with other noncardiac, intrathoracic disorders.

Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: Preliminary evidence.

Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy loss and the presence of five common Thoroughbred horse haplotypes of the equine Major Histocompatibility Complex (MHC) was assessed. This involved development of sequence specific, reverse transcriptase polymerase chain reactions and in several mares, measurement of cytotoxic T lymphocyte activity. Of the 46 mares, 10 suffered late gestation pregnancy loss or neonatal foal death, five of which were EHV-1 positive. Maternal factors including age, parity, number of EHV-1 specific vaccinations and the number of days between final vaccination and foaling or abortion were not significantly associated with pregnancy loss. In contrast, a statistically significant association between the presence of the MHC class I B2 allele and pregnancy loss was identified, regardless of the fetus/foal's EHV-1 status (p=0.002). In conclusion, this study demonstrated a significantly positive association between pregnancy loss in Thoroughbred mares and a specific MHC class I allele in the mother. This association requires independent validation and further investigation of the mechanism by which the mare's genetic background contributes to pregnancy outcome.

Increased anterior cingulate and caudate activity in bipolar mania.

BACKGROUND: Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of functional brain abnormalities in the manic state is not well understood. METHODS: We utilized a high-sensitivity H(2)(15)0 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder. RESULTS: The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate. CONCLUSIONS: The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical-subcortical neural system that includes the anterior cingulate and caudate.

Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder.

OBJECTIVE: This study investigated prefrontal cortex function in the manic state of bipolar disorder. METHOD: High-sensitivity [15O]H2O positron emission tomography and a word generation activation paradigm were used to study regional cerebral blood flow in five manic and six euthymic individuals with bipolar disorder and in five healthy individuals. RESULTS: Decreased right rostral and orbital prefrontal cortex activation during word generation and decreased orbitofrontal activity during rest were associated with mania. CONCLUSIONS: The data support the presence of rostral and orbital prefrontal dysfunction in primary mania. These findings, when seen in the context of the human brain lesion and the behavioral neuroanatomic literatures, may help to explain some of the neurobehavioral abnormalities characteristic of the manic state.

Downregulation of right ventricular phosphodiesterase PDE-3A mRNA and protein before the development of canine heart failure.

Phosphodiesterase III (PDE-3) inhibitors are inotropes used to treat congestive heart failure (HF). Previous studies showed PDE-3A mRNA levels were reduced in the left ventricle (LV) in dogs subjected to pacing-induced HF. The present study evaluated a time-course for RV-specific changes in PDE-3A mRNAs and proteins after pacing for 3 wk (n = 4) or in HF (4-5 wk; n = 4-6). Total RNA from LV/RV tissues was isolated for Northern analyses; cytosolic and microsomal proteins were prepared for PDE-3A immunoblots. PDE-3A mRNAs (7-8 and 10 kb) were normalized against glyceraldehyde-3-phosphodehydrogenase (GAPDH) or ribosomal 18s with similar results. PDE-3A/GAPDH ratios in 3 wk were unchanged in LV, but significantly (p < 0.05) reduced by 48% in RV vs unpaced controls (n = 8). In contrast, PDE-3A (7-8 kb)/GAPDH ratios were significantly reduced in HF by 50-59% in both ventricles. Consistent with mRNA levels, significant reductions in microsomal 135 kDa (93-96%) and cytosolic 120 kDa PDE-3A (57-69%) were seen in both ventricles in HF or in the RV at 3 wk; an LV-specific reduction (50%) in cytosolic 80 kDa PDE-3A in HF was also detected. In summary, RV-specific downregulation of PDE-3A mRNA/protein(s) at 3 wk suggests that hemodynamic rather than humoral mechanisms are responsible, and provides a molecular basis for the limited efficacy of milrinone in the progression of HF.

Induction of rat WT1 gene expression correlates with human chromosome 11p11.2-p12-mediated suppression of tumorigenicity in rat liver epithelial tumor cell lines.

We have previously identified and mapped a locus within human chromosome 11p11.2-p12 that suppresses the tumorigenic potential of some rat liver tumor cell lines. In the present study, possible molecular mechanisms of human 11p11.2-p12-mediated liver tumor suppression were investigated by examining gene expression patterns in suppressed and non-suppressed microcell hybrid (MCH) cell lines. The parental rat liver tumor cell lines (GN6TF and GP7TB) express moderate levels of p53 mRNA and protein, overexpress mRNAs for c-H-ras, c-myc, and TGFá, and do not express detectable levels of WT1 mRNA or protein. Suppression of tumorigenicity by human chromosome 11p11.2-p12 was not accompanied by significant alterations in the levels of expression of p53, c-myc, or TGFá. Expression of c-H-ras was decreased significantly in both suppressed and non-suppressed MCH cell lines, suggesting that down-regulation of c-H-ras is not directly responsible for tumor suppression. In contrast, the level of expression of WT1 correlated precisely with tumor suppression in this model system. All suppressed MCH cell lines expressed WT1 mRNA and protein at levels comparable to that of untransformed rat liver epithelial cells (WB-F344), whereas only trace WT1 mRNA and protein were detected in a non-suppressed MCH cell line. PCR analysis demonstrated that two suppressed MCH cell lines do not carry the human WT1 gene, indicating that WT1 expression in these lines originates from the rat locus. Furthermore, RT-PCR analysis showed that each of the four known splice variants of the WT1 mRNA are expressed in these suppressed MCH cell lines, recapitulating the expression pattern observed in the untransformed rat liver epithelial cells. Re-expression of tumorigenicity by suppressed MCH cell lines was accompanied by the coordinate loss of human chromosome 11p11.2-p12 and of WT1 gene expression, suggesting that one or more human 11p11.2-p12 genes are required for sustained expression of WT1 in these cell lines. Together, these results suggest that the molecular mechanism governing human chromosome 11p11.2-p12-mediated liver tumor suppression may involve induction of rat WT1 gene expression under the direct or indirect transcriptional regulation of a genetic locus (or loci) on human 11p11.2-p12.

Measuring hospital use without claims: a comparison of patient and provider reports.

OBJECTIVE: We compared the validity of hospital admission and length of stay reports from patients, outpatient providers, and hospitals, and we examined possible sources of error. DATA SOURCES: Data were collected from people enrolled in a randomized trial of treatment for severe mental illness and substance use disorders, from community mental health centers (CMHCs), and from hospitals. Reports for each of the 74 study participants covered two-year time periods beginning and ending at various times between 1989 and 1993. STUDY DESIGN: We compared reports from the various sources and constructed a hybrid with data from all three sources. Using parametric and non-parametric statistics, we compared patient, CMHC, and hospital reports with each other and with the hybrid source. In subsequent regression analyses we explored correlates of reporting accuracy. PRINCIPAL FINDINGS: Single-source reports underestimated hospital use, but when patient and CMHC reports were combined, results were very similar to those obtained by the more laborious hybrid method. Patient reports became less accurate as the time between discharge and reporting increased; people with bipolar disorders reported admissions with greater accuracy than did people with schizophrenia. CMHC reporting accuracy decreased as the distance to the admitting hospital increased and were less accurate for people with more severe psychiatric symptoms. CONCLUSIONS: Reports from single sources are likely to underestimate hospital use for different reasons. Combining carefully collected data from patients and outpatient providers produces estimates of hospital use that are substantially the same as those developed through methods that are more laborious and costly.

Cost-effectiveness of assertive community treatment versus standard case management for persons with co-occurring severe mental illness and substance use disorders.

OBJECTIVE: To determine the cost-effectiveness of Assertive Community Treatment (ACT) in comparison to Standard Case Management (SCM) for persons with severe mental illness and substance use disorders. DATA SOURCES AND STUDY SETTING: Original data on the effectiveness and social costs of ACT and SCM that were collected between 1989 and 1995. Seven community mental health centers in New Hampshire provided both types of treatment. STUDY DESIGN: Persons with schizophrenia, schizoaffective disorder, or bipolar disorder and a concurrent substance use disorder were randomly assigned to ACT or SCM and followed for three years. The primary variables assessed were substance use, psychiatric symptoms, functioning, quality of life, and social costs. DATA COLLECTION METHODS: Effectiveness data were obtained from interviews at six-month intervals with persons enrolled in treatment and with their service providers. Social cost and service utilization data came from client reports; interviews with informal caregivers; provider information systems and Medicaid claims; law enforcement agencies; courts; and community service providers. PRINCIPAL FINDINGS: Participants in both groups showed significant reductions in substance use over time. Focusing on quality of life and substance use outcomes, ACT and SCM were not significantly different in cost-effectiveness over the entire three-year study period. Longitudinal analyses showed that SCM tended to be more efficient during the first two years but that ACT was significantly more efficient than SCM during the final year of the study. CONCLUSIONS: In an adequately funded system, ACT is not more cost-effective than SCM. However, ACT efficiency appears to improve over time.

Legal system involvement and costs for persons in treatment for severe mental illness and substance use disorders.

OBJECTIVE: Persons with co-occurring severe mental illness and substance use disorders were followed for three years to better understand how they are involved with the legal system and to identify factors associated with different kinds of involvement. METHODS: Data came from a three-year study of 203 persons enrolled in specialized treatment for dual disorders. Cost and utilization data were collected from multiple data sources, including police, sheriffs and deputies, officers of the court, public defenders, prosecutors, private attorneys, local and county jails, state prisons, and paid legal guardians. RESULTS: Over three years 169 participants (83 percent) had contact with the legal system, and 90 (44 percent) were arrested at least once. Participants were four times more likely to have encounters with the legal system that did not result in arrest than they were to be arrested. Costs associated with nonarrest encounters were significantly less than costs associated with arrests. Mean costs per person associated with an arrest were $2,295, and mean costs associated with a nonarrest encounter were $385. Combined three-year costs averaged $2,680 per person. Arrests and incarcerations declined over time. Continued substance use and unstable housing were associated with a greater likelihood of arrest. Poor treatment engagement was associated with multiple arrests. Men were more likely to be arrested, and women were more likely to be the victims of crime. CONCLUSIONS: Effective treatment of substance use among persons with mental illness appears to reduce arrests and incarcerations but not the frequency of nonarrest encounters. Stable housing may also reduce the likelihood and number of arrests.

Biochemical markers of bone metabolism in growing thoroughbreds: a longitudinal study.

This study describes longitudinal changes in serum levels of biochemical markers of bone cell activity in a group of 24 thoroughbred foals from birth to 18 months of age. The markers of bone formation included the type I collagen carboxy-terminal propeptide (PICP), the bone-specific isoenzyme of alkaline phosphatase (BAP), and osteocalcin (OC). Levels of the cross-linked telopeptide of type I collagen (ICTP), a marker of bone resorption, and the N-terminal propeptide of type III collagen (PNIIIP), a marker of soft tissue turnover, were also measured. Levels of all markers fell significantly between birth and 18 months of age (70-80 per cent); this decrease being most marked between 0 and 6 months. However, a transient increase in levels of the markers then occurred between 6 and 14 months of age. The timing of this increase was specific for each parameter. ICTP and OC concentrations increased between October and December. PICP concentrations increased between December and April whereas the increase in PIIINP was coincident with the peak in weight gain between April and June. Changes in BAP concentration were less distinct at this time. Season was shown to have significant effects on the biochemical markers independent from the effect of age. Concentrations of all markers decreased with increasing body weight and at any given age heavier horses had lower marker levels. These results show that biochemical markers of bone cell activity and soft tissue turnover follow characteristic patterns of change in growing thoroughbreds influenced by age, season and bodyweight. The demonstration that the reference ranges for the biochemical markers change from month to month means that single samples from individuals are of little value for monitoring bone cell activity in growing thoroughbreds.

The technique and clinical appication of endometrial biopsy in the mare.

The author describes a technique for obtaining endometrail biopsy specimens from mares. the noraml cyclincal histology of the endometrium and anarbitarry classification histology of the endometrium and an arbitarary classification of the histopathology seen in endometrial biopsy speciemens. Previous literature on the subject is cited. Results of endometrial biopsies taken by the author from 134 barren mares, with histories of subfertility are descirbed and classified. The use of the technique and the interpretationof its find ings in relation to reproductive performance is discussed.

Assessment of the breeding prognosis of mares using paired endometrial biopsy techniques.

Paired endometrial biopsy samples were taken from 530 subfertile mares, before and after treatment (where indicated) and a period of sexual rest. Prognoses were made after each biopsy (Categories 1A-4A before treatment and Categories 1B-4B after treatment), using histopathological criteria similar to those described by Kenney and Doig (1986). Eighty-seven per cent of the mares were assigned to first biopsy prognosis Category 3A. The second biopsy prognosis produced a more even population distribution (10, 47, 40 and 3 per cent respectively for Category 1B, 2B, 3B and 4B mares). First biopsy Category 3A and 4A mares produced mean foaling rates of 51 and 40 per cent respectively. None of the 14 second biopsy Category 4B mares delivered a live foal (12 were barren, one aborted and one suffered early foetal death). This study supports the hypothesis that a breeding prognosis assigned on the basis of two endometrial biopsy samples, taken before and after specific uterine treatment, where indicated, which takes into consideration the mare's ability to respond to treatment, is likely to be more accurate than one assigned after a single biopsy sample.

The effect of age and parity on the development of equine chronic endometrial disease.

The results of a retrospective analysis of 3,804 endometrial biopsy specimens collected from non-pregnant mares during the course of routine equine stud farm practice demonstrates a significant and practically useful correlation between the severity of chronic degenerative endometrial disease (CDE) diagnosed and age of mare at the time of examination. There were significant correlations between the number of foals born and the mares' barren years prior to biopsy and the severity of CDE, but the differences were not sufficiently large to be useful. Correlations between the severity of chronic infiltrative endometritis (CIE) and age or pre-biopsy parity were minimal. The results suggest that using similar histopathological criteria to those used by Kenney and Doig (1986), mares up to nine years of age should have no signs of CDE, mares up to 13 years of age should have no more than mild signs, mares up to 15 years of age should have no more than moderate signs and mares aged 17 years or older are likely to have severe signs. We believe that these guidelines are a useful, objective aid for formulating a breeding prognosis.

A case of peritoneal mesothelioma in a thoroughbred mare.

The report describes a case of abdominal neoplasia in a mare diagnosed ante-mortem by the technique of paracentesis abdominis. Histopathological findings suggest that the lesion was a mesothelioma, primarily involving the greater omentum.

Haematological response to racing and training exercise in Thoroughbred horses, with particular reference to the leucocyte response.

The haematological response to racing and to fast and slow training exercise was investigated in studies involving two populations of horses which differed widely in geographical location, climatic factors and management (Newmarket and Hong Kong). The well documented elevations in erythrocyte parameters were demonstrated and changing responses in leucocyte parameters, resulting in variations in the neutrophil to lymphocyte (N/L) ratio were described. It was shown that the immediate response to the anticipation or stress of exercise was a decrease in N/L ratio in association with an increase in lymphocyte numbers. The magnitude of the lymphocyte increases was similar in the two populations of horses producing a reversal of the N/L ratio (lymphocytes predominating) in the British but not the Hong Kong horses, owing to the higher resting ratio of the latter population. At 3 and 4 h after exercise, an increase in N/L ratio occurred in association with an increase in neutrophils and decrease in lymphocytes. All parameters had returned to resting level by 6 h following exercise. Those and the many other factors associated with alterations in equine N/L ratios are discussed in terms of the need for care when interpreting the results of haematological examinations.

Concentrations of uterine luminal prostaglandins in mares with acute and persistent endometritis.

Intrauterine infusion of 1 per cent oyster glycogen solution was used to induce acute endometritis in four genitally normal mares. Numbers of viable neutrophils recovered in uterine washings had increased by 1 h after infusion and remained elevated for at least 72 h. There was a significant correlation between numbers of viable neutrophils and total protein concentrations and between prostaglandin (PG)F and PGE2 concentrations in washings. There was also a significant relationship between concentrations of 15-keto-13, 14-dihydro PGF2 alpha in plasma and PGF in washings. Intrauterine concentrations of PGF were influenced by cycle stage and in turn the induced acute endometritis interfered with normal ovarian function. Mares with persistent endometritis had significantly higher concentrations of PGF and total protein and percentage of neutrophils and mononuclear cells in washings than normal mares. White blood cells from mares were capable of producing PGF and PGE2 in vitro.

Investigation of association between alpha-1 proteinase inhibitor haplotype and endometritis in the thoroughbred mare.

Failure to inhibit proteinases can lead to excessive tissue damage. The possibility that the severity of endometritis in Thoroughbred mares correlates with the haplotypes of plasma alpha 1-proteinase inhibitor (alpha 1-PI) expressed was investigated in two groups of mares. In mares with pyometritis before treatment, the frequency of the N haplotype, which is already high in the Thoroughbred population, was significantly increased when compared with that in a large published population. In mares with acute endometritis which persisted after treatment followed by sexual rest, the absence of S and T haplotypes was significant, suggesting that, when present, they may have a protective function.