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

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

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

An appraisal of analytical tools used in predicting clinical outcomes following radiation therapy treatment of men with prostate cancer: a systematic review

Background: Prostate cancer can be treated with several different modalities, including radiation treatment. Various prognostic tools have been developed to aid decision making by providing estimates of the probability of different outcomes. Such tools have been demonstrated to have better prognostic accuracy than clinical judgment alone. Methods: A systematic review was undertaken to identify papers relating to the prediction of clinical outcomes (biochemical failure, metastasis, survival) in patients with prostate cancer who received radiation treatment, with the particular aim of identifying whether published tools are adequately developed, validated, and provide accurate predictions. PubMed and EMBASE were searched from July 2007. Title and abstract screening, full text review, and critical appraisal were conducted by two reviewers. A review protocol was published in advance of commencing literature searches. Results: The search strategy resulted in 165 potential articles, of which 72 were selected for full text review and 47 ultimately included. These papers described 66 models which were newly developed and 31 which were external validations of already published predictive tools. The included studies represented a total of 60,457 patients, recruited between 1984 and 2009. Sixty five percent of models were not externally validated, 57% did not report accuracy and 31% included variables which are not readily accessible in existing datasets. Most models (72, 74%) related to external beam radiation therapy with the remainder relating to brachytherapy (alone or in combination with external beam radiation therapy). Conclusions: A large number of prognostic models (97) have been described in the recent literature, representing a rapid increase since previous reviews (17 papers, 1966–2007). Most models described were not validated and a third utilised variables which are not readily accessible in existing data collections. Where validation had occurred, it was often limited to data taken from single institutes in the US. While validated and accurate models are available to predict prostate cancer specific mortality following external beam radiation therapy, there is a scarcity of such tools relating to brachytherapy. This review provides an accessible catalogue of predictive tools for current use and which should be prioritised for future validation.Elspeth Raymond, Michael E. O’Callaghan, Jared Campbell, Andrew D. Vincent, Kerri Beckmann, David Roder, Sue Evans, John McNeil, Jeremy Millar, John Zalcberg, Martin Borg and Kim Morett

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

Transferred III-V materials - novel devices and integration

Separating the substrate allows thin layers of III-V photonic semiconductor materials and devices to be integrated on foreign templates using transfer-printing. We demonstrate advanced light emitting and detecting devices based on this principle