Increasing the efficacy of Judas goats by sterilisation and pregnancy termination

The use of Judas goats to locate remnant animals is a potentially powerful tool for enhancing goat-eradication efforts, which are especially important to island conservation. However, current Judas goat methodology falls short of its potential efficacy. Female Judas goats are often pregnant at the time of deployment or become impregnated in the field; pregnant females leave associated goats to give birth, causing downtime of Judas goat operations. Further, male Judas goats may inseminate remnant females. Sterilising Judas goats prior to deployment removes these inefficiencies. Here, we describe two methods (epididymectomy for males and tubal occlusion for females) that sterilise Judas goats while still maintaining sexual motivation and other behaviours associated with intact animals. These surgeries are straightforward, time efficient, and may be conducted in the field by staff with minimal training. Given the widespread and deleterious impacts of non-native herbivores to ecosystems and the importance of Judas operations in detecting animals at low densities, sterilisation and termination of pregnancy should be applied routinely in Judas goat (and possibly other species) programs to increase the efficacy of low-density control operations and eradication campaigns.

Use of umbilical artery Doppler velocimetry in the monitoring of pregnancy in women with pre-existing diabetes

Background: The usefulness of umbilical artery Doppler velocimetry for the monitoring of diabetic pregnancies is controversial. The aim of the present study was to assess whether umbilical artery Doppler velocity waveform analysis can predict adverse perinatal outcomes for pregnancies complicated by pre-existing diabetes mellitus. Methods: All diabetic pregnancies (type 1 and 2) delivered at Mater Mothers' Hospital, Queensland, between 1 January 1995 and 31 December 1999 were included. All pregnant diabetic women were monitored with umbilical artery Doppler velocimetry at 28, 32, 36, and 38 weeks' gestation. Adverse perinatal outcome was defined as pregnancies with one or more of the following: small-for-gestational age, Caesarean section for non-reassuring cardiotocography, fetal acidaemia at delivery, 1-min Apgar of 3 or less, 5-min Apgar of less than 7, hypoxic ischaemic encephalopathy or perinatal death. Abnormal umbilical artery Doppler velocimetry was defined as a pulsatility index of 95th centile or higher for gestation. Results: One hundred and four pregnancies in women with pre-existing diabetes had umbilical arterial Doppler studies carried out during the study period. Twenty-three pregnancies (22.1%) had an elevated pulsatility index. If the scans were carried out within 2 weeks of delivery, 71% of pregnancies with abnormal umbilical Doppler had adverse outcomes (P < 0.01; likelihood ratio, 4.2). However, the sensitivity was 35%; specificity was 94%; positive predictive value was 80%; and negative predictive value was 68%. Only 30% of women with adverse perinatal outcomes had abnormal umbilical arterial Doppler flow. Conclusion: Umbilical artery Doppler velocimetry is not a good predictor of adverse perinatal outcomes in diabetic pregnancies.

Socioeconomic position, cognitive function, and clustering of cardiovascular risk factors in adolescence: Findings from the Mater University Study of Pregnancy and its outcomes

Objectives: The objectives of this study were to examine the extent of clustering of smoking, high levels of television watching, overweight, and high blood pressure among adolescents and whether this clustering varies by socioeconomic position and Cognitive function. Methods: This study was a cross-sectional analysis of 3613 (1742 females) participants of an Australian birth cohort who were examined at age 14. Results: Three hundred fifty-three (9.8%) of the participants had co-occurrence of three or four risk factors. Risk factors clustered in these adolescents with a greater number of participants than would be predicted by assumptions of independence having no risk factors and three or four risk factors. The extent of clustering tended to be greater in those from lower-income families and among those with lower cognitive function. The age-adjusted ratio of observed to expected cooccurrence of three or four risk factors was 2.70 (95% confidence interval [Cl], 1.80-4.06) among those from low-income families and 1.70 (95% Cl, 1.34-2.16) among those from more affluent families. The ratio among those with low Raven's scores (nonverbal reasoning) was 2.36 (95% Cl, 1.69-3.30) and among those with higher scores was 1.51 (95% Cl, 1.19-1.92); similar results for the WRAT 3 score (reading ability) were 2.69 (95% Cl, 1.85-3.94) and 1.68 (95% Cl, 1.34-2.11). Clustering did not differ by sex. Conclusion: Among adolescents, coronary heart disease risk factors cluster, and there is some evidence that this clustering is greater among those from families with low income and those who have lower cognitive function.

Termination of real-time programs: Definitely, definitely not, or maybe

Real-time control programs are often used in contexts where (conceptually) they run forever. Repetitions within such programs (or their specifications) may either (i) be guaranteed to terminate, (ii) be guaranteed to never terminate (loop forever), or (iii) may possibly terminate. In dealing with real-time programs and their specifications, we need to be able to represent these possibilities, and define suitable refinement orderings. A refinement ordering based on Dijkstra's weakest precondition only copes with the first alternative. Weakest liberal preconditions allow one to constrain behaviour provided the program terminates, which copes with the third alternative to some extent. However, neither of these handles the case when a program does not terminate. To handle this case a refinement ordering based on relational semantics can be used. In this paper we explore these issues and the definition of loops for real-time programs as well as corresponding refinement laws.

Treatment of maternal syphilis in rural South Africa: effect of multiple doses of benzathine penicillin on pregnancy loss

OBJECTIVES Despite few data, the treatment of syphilis in pregnant women using a single dose of benzathine penicillin is the standard of care in many resource-poor settings. We examined the effect of various doses of benzathine penicillin on pregnancy loss among women with a positive Rapid Plasma Reagin (RPR) test result in a rural South African district. METHODS All pregnant women making their first antenatal care visit during pregnancy were screened for syphilis using the RPR test. Those testing positive were counselled to receive three weekly doses of benzathine penicillin, and received a partner notification card. Pregnancy outcomes were determined from facility records or home visits where necessary. RESULTS Of 8917 women screened, 1043 (12%) had reactive syphilis serology; of those with titre data available, 30% had titres of 1:8 or greater. While 41% (n = 430) of women received all three doses as counselled, 30% (n = 312) received only one dose, and 20% (n = 207) did not return to the clinic to receive treatment. Among the 947 women with pregnancy outcome data available, there were 17 miscarriages and 48 perinatal deaths observed. There was a strong trend towards reduced risk of pregnancy loss among women receiving multiple doses of penicillin (adjusted OR for perinatal mortality for each additional dose received, 0.63; 95% CI, 0.48-0.84). CONCLUSIONS While this association requires further investigation, these results suggest that there may be substantial benefit to providing multiple doses of benzathine penicillin to treat maternal syphilis in this setting.

Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy

To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal history, and environmental factors. A prospective, observational, community-based cohort study. Methods. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes. Results. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (116.0%) compared with those exposed to all other AEDs (16.0% vs. 2.4%, P < 0.01) or no AEDs (16.0% vs. 3.1 %, P < 0.01). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (11975 vs: 1128 mg, P < 0.01). The incidence of FM with VPA doses greater than or equal to 1100 mg was 30.2% vs. 3.2% with doses < 1100 mg (P < 0.01). Conclusions. There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy. (C) 2004 Elsevier Ltd. All rights reserved.

Population pharmacokinetics of metformin in late pregnancy

The pharmacokinetic disposition of metformin in late pregnancy was studied together with the level of fetal exposure at birth. Blood samples were obtained in the third trimester of pregnancy from women with gestational diabetes or type 2 diabetes, 5 had a previous diagnosis of polycystic ovary syndrome. A cord blood sample also was obtained at the delivery of some of these women, and also at delivery of others who had been taking metformin during pregnancy but from whom no blood had been taken. Plasma metformin concentrations were assayed by a new, validated, reverse-phase HPLC method, A 2-compartment, extravascular maternal model with transplacental partitioning of drug to a fetal compartment was fitted to the data. Nonlinear mixed-effects modeling was performed in'NONMEM using FOCE with INTERACTION. Variability was estimated using logarithmic interindividual and additive residual variance models; the covariance between clearance and volume was modeled simultaneously. Mean (range) metformin concentrations in cord plasma and in maternal plasma were 0.81 (range, 0.1-2.6) mg/L and 1.2 (range, 0. 1-2.9) mg/L, respectively. Typical population values (interindividual variability, CV%) for allometrically scaled maternal clearance and volume of distribution were 28 L/h/70 kg (17.1%) and 190 L/70 ka (46.3%), giving a derived population-wide half-life of 5.1 hours. The placental partition coefficient for metformin was 1.07 (36.3%). Neither maternal age nor weight significantly influenced the pharmacokinetics. The variability (SD) of observed concentrations about model-predicted concentrations was 0.32 mg/L. The pharmacokinetics were similar to those in nonpregnant patients and, therefore, no dosage adjustment is warranted. Metformin readily crosses the placenta, exposing the fetus to concentrations approaching those in the maternal circulation. The sequelae to such exposure, ea, effects on neonatal obesity and insulin resistance, remain unknown.

Relationship of body condition score and blood urea and ammonia to pregnancy in Italian Mediterranean buffaloes

The relationship of body condition score ( BCS) and blood urea and ammonia to pregnancy outcome was examined in Italian Mediterranean Buffalo cows mated by AI. The study was conducted on 150 buffaloes at 145 +/- 83 days in milk that were fed a diet comprising 14.8% crude protein, 0.9 milk forage units . kg(-1) dry matter and a non- structural carbohydrate/ crude protein ratio of 2.14. The stage of the oestrous cycle was synchronised by the Ovsynch- TAI programme and blood urea and ammonia levels were assessed on the day of AI. Energy corrected milk ( ECM) production and BCS were recorded bi- weekly. The pregnancy risk was 46.7% and was slightly lower in buffaloes with BCS < 6.0 and BCS > 7.5. There were no significant differences in ECM, urea and ammonia between pregnant and non- pregnant buffaloes. However, pregnancy outcome was higher ( P = 0.02) in buffaloes with blood urea < 6.83 mmol . L-1. The likelihood of pregnancy for buffaloes with low urea blood level was 2.6 greater than for high urea level and exposure to a high urea level lowered the probability of pregnancy by about 0.25. The findings indicate that buffaloes are similar to cattle and increased blood levels of urea are associated with reduced fertility when animals are mated by AI.

Isolation of an imaginal disc growth factor homologue from Pieris rapae and its expression following parasitization by Cotesia rubecula

Endoparasitoid insects introduce maternal factors into the body of their host at oviposition to suppress cellular defences for the protection of the developing parasitoid. We have shown that transient expression of polydnavirus genes from a hymenopteran parasitoid Cotesia rubecula (CrPDV) is responsible for the inactivation of hemocytes from the lepidopteran host Pieris rapae. Since the observed downregulation of CrPDV genes in infected host tissues is not due to cis-regulatory elements at the CrV1 gene locus, we speculated that the termination of CrPDV gene expression may be due to cellular inactivation caused by the CrV1-mediated immune suppression of infected tissues. To test this assumption, we isolated an imaginal disc growth factor (IDGF) that is expressed in fat body and hemocytes, the target of viral infection and expression of CrPDV genes. Time-course experiments showed that the level of P. rapae IDGF is not affected by parasitization and polydnavirus infection. However, the amount of highly expressed genes, such as storage proteins, arylphorin and lipophorin, are significantly reduced following parasitization. (C) 2004 Elsevier Ltd. All rights reserved.

The generational transmission of socioeconomic inequalities in child cognitive development and emotional health

Socioeconomic inequalities in the health of adults have been largely attributed to lifestyle inequalities. The cognitive development (CD) and emotional health (EH) of the child provides a basis for many of the health-related behaviours which are observed in adulthood. There has been relatively little attention paid to the way CID and EH are transmitted in the foetal and childhood periods, even though these provide a foundation for subsequent socioeconomic inequalities in adult health. The Mater-University of Queensland Study of Pregnancy (MUSP) is a large, prospective, pre-birth cohort study which enrolled 8556 pregnant women at their first clinic visit over the period 1981-1983. These mothers (and their children) have been followed up at intervals until 14 years after the birth. The socioeconomic status of the child was measured using maternal age, family income, and marital status and the grandfathers' occupational status. Measures of child CD and child EH were obtained at 5 and 14 years of age. Child smoking at 14 years of age was also determined. Family income was related to all measures of child CD and EH and smoking, independently of all other indicators of the socioeconomic status of the child. In addition, the grandfathers' occupational status was independently related to child CD (at 5 and 14 years of age). Children from socioeconomically disadvantaged families (previous generations' socioeconomic status as well as current socioeconomic status) begin their lives with a poorer platform of health and a reduced capacity to benefit from the economic and social advances experienced by the rest of society. (C) 2003 Elsevier Ltd. All rights reserved.

Canine model for investigating the impact of oral enrofloxacin on commensal coliforms and colonization with multidrug-resistant Escherichia coli

A model was developed in dogs to determine the impact of oral enrofloxacin administration on the indigenous coliform population in the gastrointestinal tract and subsequent disposition to colonization by a strain of multidrug-resistant Escherichia coli (MDREC). Dogs given a daily oral dose of 5 mg enrofloxacin kg(-1) for 21 consecutive days showed a significant decline in faecal coliforms to levels below detectable limits by 72 In of administration. Subsequently, faecal coliforms remained suppressed throughout the period of enrofloxacin dosing. Upon termination of antibiotic administration, the number of excreted faecal coliforms slowly returned over an 8-day period, to levels comparable to those seen prior to antibiotic treatment. Enrofloxacin-treated dogs were more effectively colonized by MDREC, evidenced by a significantly increased count of MDREC in the faeces (7.1 +/- 1.5 log(10) g(-1)) compared with non-antibiotic-treated dogs (5.2 +/- 1.2; P = 0.003). Furthermore, antibiotic treatment also sustained a significantly longer period of MDREC excretion in the faeces (26.8 +/- 10.5 days) compared with animals not treated with enrofloxacin (8.5 +/- 5.4 days; P = 0.0215). These results confirm the importance of sustained delivery of an antimicrobial agent to maintain and expand the colonization potential of drug-resistant bacteria in vivo, achieved in part by reducing the competing commensal coliforms in the gastrointestinal tract to below detectable levels in the faeces. Without in vivo antimicrobial selection pressure, commensal coliforms dominated the gastrointestinal tract at the expense of the MDREC population. Conceivably, the model developed could be used to test the efficacy of novel non-antibiotic strategies aimed at monitoring and controlling gastrointestinal colonization by multidrug-resistant members of the Enterobacteriaceae that cause nosocomial infections.

Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.

The effects of intra-amniotic injection of periodontopathic lipopolysaccharides in sheep

Objective: Periodontal disease may cause several complications of pregnancy, including fetal death. The purpose of this study was to investigate in sheep the effects of the intra-amniotic injection of lipopolysaccharide from 3 periodontopathic organisms and to compare these effects with those resulting from similar injection of Escherichia coli lipopolysaccharide. The outcomes that were studied included the rates of fetal death and the features of inflammation and lung maturation in survivors. Study design: At 118 days of pregnancy, ewes that were bearing single fetuses were allocated at random to receive intra-amniotic injections of saline solution (n = 13 fetuses), or lipopolysaccharide from Porphyromonas gingivalis (in doses from 0.1 to 10 tug [n = 22 fetuses]), Actinobacillus actinomycetemcomitans (10 mg [n = 6 fetuses]; 1 mg [n = 6 fetuses]), Fusobacterium nucleation (10 mg [n = 6 fetuses]) or Escherichia coli (10 mg [n = 14 fetuses]; 1 mg [n = 7 fetuses]). Surviving fetuses were delivered abdominally at 125 days of gestation (term, 150 days). Results: When compared with Escherichia coli lipopolysaccharide at similar dosages, periodontopathic lipopolysaccharides had high rates of fetal lethality. Only 6 of 22 fetuses that were exposed to intra-amniotic Porphyromonas gingivalis lipopolysaccharide survived doses of 0.1 to 10 mg, and only 3 of 6 fetuses survived 10-mg Actinobacillus actinomycetemcomitans lipopolysaccharide. Escherichia coli lipopolysaccharide did not cause fetal loss when given at doses of 10 mg (n = 14 fetuses) or l mg (n = 7 fetuses). Fetuses that survived exposure to these lipopolysaccharides showed features of inflammation in amniotic fluid and cord blood at birth and enhanced lung maturation. Conclusion: Lipopolysaccharides from these 3 periodontopathic organisms have much higher rates of fetal lethality than Escherichia coli lipopolysaccharide but can cause similar intrauterine inflammatory responses and improvements in lung volumes in survivors. Sources of inflammation that are distant from the uterus may underlie a proportion of unexplained stillbirth and other complications of pregnancy. (c) 2005 Mosby, Inc. All rights reserved.