Differences in the epidemiology of theileriosis on smallholder dairy farms in contrasting agro-ecological and grazing strata of highland Kenya

A prospective cohort study was conducted in five purposively-sampled agro-ecological zone (AEZ)-grazing system strata in Murang’a District, Kenya, between March 1995 and June 1996. The study strata were selected based on a preliminary characterization study to represent the widest range of risks to East Coast fever (ECF) in the District and included zero-grazing and open-grazing farms. In total, 225 calves from 188 smallholder farms were examined from birth to 6 months of age and visited within the first 2 weeks of life and thereafter at bi-weekly intervals for up to 14 visits. The purpose of the study was to characterize the differences in epidemiology (risks of infection, morbidity and mortality) and potential control of ECF between the selected strata. Evidence of Theileria parva infection was assessed by increased antibody levels as measured in an indirect ELISA assay by the percent positivity (PP) of serum samples relative to a strong positive reference serum. Sero-conversion risks of T. parva were highest in the open-grazing strata. Antibody prevalence in adult cattle and ECF morbidity and mortality risks were also highest in open-grazing strata. While different, all five AEZ-grazing strata were considered to be endemically unstable for ECF. East Coast fever challenge was low in all zero-grazing strata and this challenge is likely to remain low due to continuing intensification of smallholder farming in the central highlands. In the open-grazing strata, there was higher challenge and a greater impact of ECF. ILRI publication no.: 99017

Intrauterine Growth and Intelligence Within Sibling Pairs: Findings From the Mater-University Study of Pregnancy and its Outcomes

Objective: To examine the association between intrauterine growth and intelligence. Design: Population based birth cohort study of sibling pairs born within a maximum of three years of each other. Setting: Mater-University women and children's hospital, Brisbane, Australia. Participants: 235 (470 children) sibling pairs. Results: Among one randomly selected sibling from each pair verbal comprehension at age 5, general intelligence at age 14, and reading ability at age 14 increased linearly with increasing gestational age and sex standardised birth weight z scores. With adjustment for maternal age, race, and smoking during pregnancy, birth order, family income, and parental education the associations with verbal comprehension at age 5 and general intelligence at age 14 remained, whereas the association with reading ability at age 14 was attenuated to the null. Within sibling pairs, differences in intrauterine growth were positively associated with differences in verbal comprehension at age 5 (test score difference per one unit difference in birth weight z score = 1.52 (0.11 to 3.26)) and general intelligence at age 14 (1.09 (0.01 to 2.18)), but not with reading ability at age 14. Conclusions: Socioeconomic position or other fixed maternal characteristics do not seem to explain the positive association between intrauterine growth and childhood intelligence

The role of intratidal oscillations in sediment resuspension in a diurnal, partially mixed estuary

Using detailed observations of the mean and turbulent properties of flow, salinity and turbidity that spanned 2001/02, we examined the physical mechanisms underpinning sediment resuspension in the low-energy Swan River estuary, Western Australia. In this diurnal tidally-dominated estuary, the presence of intratidal oscillations, a tidal inequality lasting 2 to 3 hours on the flood tide, generated by interactions of the four main diurnal and semidiurnal astronomical constituents, K₁, O₁, M₂, and S₂, played a major role in modifying vertical stratification and mixing. These intratidal oscillations are controlled by phase differences between the tropic and synodic months rather than being temporally-fixed by bed friction, as occurs in semidiurnal estuaries. Intratidal oscillations are largest, at around 0.1 m, near to the Austral solstice when the lunar and solar declination are in-phase. Despite the seemingly small change in water level, shear-induced interfacial mixing caused destratification of the water column with the top-to-bottom salinity (ΔS) difference of 3.5 present early in the flood tide eroded to less than 0.3 by the end of the intratidal oscillation. High turbidity peaks, of 250 nephelometric turbidity units, coincided with these intratidal oscillations and could not be explained by bed friction since shear stress from mean flow did not exceed threshold criteria. High Reynolds stresses of ∼1 Nm⁻² did, however, exceed τcr and together with negative Reynolds fluxes indicate a net downward transport of material. Destratification of the water column induced by shear instabilities resulted in large overturns capable of moving in situ material towards the bed during intratidal oscillations and these turbidities were ∼10 times greater than those from bed-generated resuspension observed later during the flood tide

A randomized clinical trial of methylnaltrexone for the treatment of opioid induced constipation & gastrointestinal stasis in intensive care patients; results from the MOTION trial

PurposeConstipation can be a significant problem in critically unwell patients, associated with detrimental outcomes. Opioids are thought to contribute to the mechanism of bowel dysfunction. We tested if methylnaltrexone, a pure peripheral mu-opioid receptor antagonist, could reverse opioid induced constipationMethodsThe MOTION trial is a multi-centre, double blind, randomised placebo controlled trial to investigate whether methylnaltrexone alleviatesopioid induced constipation (OIC) in critical care patients. Eligibility criteria included adult ICU patients who were mechanically ventilated, receiving opioids and were constipated (had not opened bowels for a minimum 48 hours) despite prior administration of regular laxatives as per local bowel management protocol. The primary outcome was time to significant rescue-free laxation. Secondary outcomes included gastric residual volume, tolerance of enteral feeds, requirement for rescue laxatives, requirement for prokinetics, average number of bowel movements per day,escalation of opioid dose due to antagonism/reversal of analgesia, incidence of ventilator-associated pneumonia, incidence of diarrhoea and Clostridium difficileinfection and finally 28 day, ICU and hospital mortality.ResultsA total of 84 patients were enrolled and randomized (41 to methylnaltrexone and 43 to placebo). The baseline demographic characteristics of the two groups were generally well balanced. There was no significant differencein time to rescue-free laxation between the groups (Hazard ratio 1.42, 95%CI 0.82-2.46, p=0.22). There were no significant differencesin the majority of secondary outcomes, particularly days 1-3. However, during days 4-28, there were fewer median number of bowel movements per day in the methylnaltrexone group, (p=0.01) and a greater incidence of diarrhoea in the placebo group (p=0.02). There was a marked difference in mortality between the groups, with ten deaths in the methylnaltrexone group and two in the placebo group during days 4-28. (p=0.007).ConclusionWe found no evidence to support the addition of methylnaltrexone to regular laxatives for the treatment of opioidinduced constipation in critically ill patients, however the confidence interval was wide and a clinically important difference cannot be excluded

Circannual Alterations in the Circadian Rhythm of Melatonin Secretion

To determine if a circadian rhythm known to be functionally related to the reproductive axis varies on a circannual basis, we monitored the circadian secretion of melatonin at monthly intervals for 2 years in four ovariectomized, estradiol-implanted ewes held in a constant short-day photoperiod. Prior to the study, ewes had been housed in a short-day (8L:16D) photoperiod for 4 years and were exhibiting circannual reproductive rhythms as assessed by serum luteinizing hormone (LH) levels. Three of the four sheep showed unambiguous deviations from the expected nocturnal melatonin secretion at two different times approximately 1 year apart. Nocturnal rises in melatonin, which usually last the duration of the dark phase, were delayed by 3-14 h or were missing. Altogether, five of the seven melatonin alterations observed in these three ewes occurred during the nadir of the circannual LH cycle. In the remaining ewe, we did not observe an altered melatonin secretory pattern during this period, and this ewe also failed to show a high amplitude circannual cycle of LH. The results provide evidence for a circannual change in the circadian rhythm of melatonin secretion. This alteration in melatonin secretion may serve as a "functional" change in daylength, and thereby may influence the expression of the circannual reproductive rhythm of sheep held in a fixed photoperiod for an extended time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68029/2/10.1177_074873049501000104.pd

Non-invasive measurement of hepatic venous oxygen saturation (ShvO₂) with quantitative susceptibility mapping in normal mouse liver and livers bearing colorectal metastases

PURPOSE: The purpose of this prospective study was to investigate the potential of QSM to noninvasively measure hepatic venous oxygen saturation (ShvO2). Materials & Methods: All animal studies were performed in accordance with the UK Home Office Animals Science Procedures Act (1986) and UK National Cancer Research Institute (NCRI) guidelines. QSM data was acquired from a cohort of mice (n=10) under both normoxic (medical air, 21% O2/balance N), and hyperoxic conditions (100% O2). Susceptibility measurements were taken from large branches of the portal and hepatic vein under each condition and were used to calculate venous oxygen saturation in each vessel. Blood was extracted from the IVC of three mice under norm- and hyperoxic conditions, and oxygen saturation was measured using a blood gas analyser to act as a gold standard. QSM data was also acquired from a cohort of mice bearing colorectal liver metastases (CRLM). SvO2 was calculated from susceptibility measurements made in the portal and hepatic veins, and compared to the healthy animals. RESULTS: SvO2 calculated from QSM measurements showed a significant increase of 14.93% in the portal vein (p < 0.05), and an increase of 21.39% in the hepatic vein (p < 0.01). Calculated results showed excellent agreement with those from the blood gas analyser (26.14% increase). ShvO2 was significantly lower in the disease cohort (30.18 ± 11.6%), than the healthy animals (52.67 ± 17.8%) (p < 0.05), but differences in the portal vein were not significant. CONCLUSION: QSM is a feasible tool for non-invasively measuring hepatic venous oxygen saturation and can detect differences in oxygen consumption in livers bearing colorectal metastases

Supporting future scholars of engaged research

Researchers in the UK are taking on new roles and responsibilities to meet the requirements of an expanded agenda for generating and evidencing social and economic impacts from research. Within this wider context, culture change programmes have identified learning as an important driver of change. Here we outline a professional development programme designed to train postgraduate researchers studying environmental sciences in core engagement, influence and impact, governance and organization skills for research. We argue that training is an important step in further catalysing progressive culture change. However, our research- and experience-informed critical reflections in supporting researchers suggest that there is still significant work to be done: (1) to offer consistent messages to researchers at all grades about social impacts from research and (2) to ensure that engagement is seen as an aspirational activity, embedded within research

Light drinking in pregnancy, a risk for behavioural problems and cognitive deficits at 3 years of age?

Background The objective of this study was to determine whether there was an association between mothers’ light drinking during pregnancy and risk of behavioural problems, and cognitive deficits in their children at age 3 years. Methods Data from the first two sweeps of the nationally representative prospective UK Millennium Cohort study were used. Drinking patterns during pregnancy and behavioural and cognitive outcomes were assessed during interviews and home visits. Behavioural problems were indicated by scores falling above defined clinically 15 relevant cut-offs on the parent-report version of the Strengths and Difficulties Questionnaire (SDQ). Cognitive ability was assessed using the naming vocabulary subscale from the British Ability Scale (BAS) and the Bracken School Readiness Assessment (BSRA). Results There was a J-shaped relationship between mothers drinking 20 during pregnancy and the likelihood of high scores (above the cut-off) on the total difficulties scale of the SDQ and the conduct problems, hyperactivity and emotional symptom SDQ subscales. Children born to light drinkers were less likely to score above the cut-offs compared with children of abstinent mothers. Children 25 born to heavy drinkers were more likely to score above the cut-offs compared with children of abstinent mothers. Boys born to mothers who had up to 1–2 drinks per week or per occasion were less likely to have conduct problems (OR 0.59, 95% CI 0.45–0.77) and hyperactivity (OR 0.71, 95% CI 0.54–0.94). These effects remained 30 in fully adjusted models. Girls were less likely to have emotional symptoms (OR 0.72, 95% CI 0.51–1.01) and peer problems (OR 0.68, 95% CI 0.52–0.92) compared with those born to abstainers. These effects were attenuated in fully adjusted models. Boys born to light drinkers had higher cognitive ability test scores [standard 35 deviations, (95% CI)] BAS 0.15 (0.08–0.23) BSRA 0.24 (0.16–0.32) compared with boys born to abstainers. The difference for BAS was attenuated on adjustment for socio-economic factors, whilst the difference for BSRA remained statistically significant. Conclusions Children born to mothers who drank up to 1–2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of abstinent mothers. Heavy drinking 5 during pregnancy appears to be associated with behavioural problems and cognitive deficits in offspring at age 3 years whereas light drinking does not

Specialised information processing deficits and distinct metabolomics profiles following TM-domain disruption of Nrg1

While there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signalling in schizophrenia. The present study focused on specialised behavioural and characterisation of hitherto un-characterised information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain. Across two different sites and protocols, Nrg1 mutants demonstrated deficits in pre-pulse inhibition, a measure of sensorimotor gating that is disrupted in schizophrenia; these deficits were partially reversed by acute treatment with second-, but not first-, generation antipsychotic drugs. However, Nrg1 mutants did not show a specific deficit in latent inhibition, a measure of selective attention that is also disrupted in schizophrenia. In contrast, in the ‘what-where-when’ cognitive paradigm, Nrg1 mutants displayed sex-specific (males only) disruption of ‘what-when’ performance, indicative of impaired episodic memory. Differential metabolomic profiling revealed that these behavioural phenotypes were accompanied, most prominently, by alterations in lipid metabolism pathways. This study is the first to associate these novel physiological mechanisms, previously independently identified as being abnormal in schizophrenia, with disruption of NRG1 function. These data suggest novel mechanisms by which compromised neuregulin function from birth might lead to schizophrenia-relevant behavioural changes in adulthood