Ontogeny of midazolam glucuronidation in preterm infants

Purpose: In preterm infants, the biotransformation of midazolam (M) to 1-OH-midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam glucuronide (OHMG) is also decreased. The aim of our study was to investigate the urinary excretion of midazolam and its metabolites OHM and OHMG in preterm neonates following the intravenous (IV) or oral (PO) administration of a single M dose. Methods: Preterm infants (post-natal age 3-13 days, gestational age 26-34 4/7 weeks) scheduled to undergo a stressful procedure received a 30-min IV infusion (n=15) or a PO bolus dose (n=7) of 0.1 mg/kg midazolam. The percentage of midazolam dose excreted in the urine as M, OHM and OHMG up to 6 h post-dose was determined. Results: The median percentage of the midazolam dose excreted as M, OHM and OHMG in the urine during the 6-h interval after the IV infusion was 0.44% (range 0.02-1.39%), 0.04% (0.01-0.13%) and 1.57% (0.36-7.7%), respectively. After administration of the PO bolus dose, the median percentage of M, OHM and OHMG excreted in the urine was 0.11% (0.02-0.59%), 0.02% (0.00-0.10%) and 1.69% (0.58-7.31%), respectively. The proportion of the IV midazolam dose excreted as OHMG increased significantly with postconceptional age (r=0.73, p <0.05). Conclusion: The glucuronidation of OHM appears immature in preterm infants less than 2 weeks of age. The observed increase in urinary excretion of OHMG with postconceptional age likely reflects the combined maturation of glucuronidation and renal function

The formation, properties and impact of secondary organic aerosol: current and emerging issues

Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed

The Maximal Runaway Temperature of Earth-like Planets

We generalize the problem of the semi-gray model to cases in which a non-negligible fraction of the stellar radiation falls on the long-wavelength range, and/or that the planetary long-wavelength emission penetrates into the transparent short wavelength domain of the absorption. Second, applying the most general assumptions and independently of any particular properties of an absorber, we show that the greenhouse effect saturates and any Earth-like planet has a maximal temperature which depends on the type of and distance to its main-sequence star, its albedo and the primary atmospheric components which determine the cutoff frequency below which the atmosphere is optically thick. For example, a hypothetical convection-less planet similar to Venus, that is optically thin in the visible, could have at most a surface temperature of 1200-1300K irrespective of the nature of the greenhouse gas. We show that two primary mechanisms are responsible for the saturation of the runaway greenhouse effect, depending on the value of the wavelength above which the atmosphere becomes optically thick. Unless this wavelength is small and resides in the optical region, saturation is achieved by radiating the thermal flux of the planet through the short wavelength tail of the thermal distribution. This has the observational implication, the radiation from such a planet should be skewed towards the NIR. Otherwise, saturation takes place by radiating through windows in the FIR.Comment: 13 pages 14 figure

The Role of Saliency in Learning First Words

In word learning, one key accomplishment is the reference, that is, the linking of a word to its referent. According to classical theories, the term reference captures a mental event: A person uses a word to mentally recall a concept of an entity (an object or event) in order to bring it into the mental focus of an interaction. The developmental literature proposes different approaches regarding how children accomplish this link. Although researchers agree that multiple processes (within and across phonological, lexical, and semantic areas) are responsible for word learning, recent research has highlighted the role of saliency and perception as crucial factors in the early phases of word learning. Generally speaking, whereas some approaches to solving the reference problem attribute a greater role to the referent’s properties being salient, others emphasize the social context that is needed to select the appropriate referent. In this review, we aim to systematize terminology and propose that the reason why assessments of the impact of saliency on word learning are controversial is that definitions of the term saliency reveal different weightings of the importance that either perceptual or social stimuli have for the learning process. We propose that defining early word learning in terms of paying attention to salient stimuli is too narrow. Instead, we emphasize that a new link between a word and its referent will succeed if a stimulus is relevant for the child

Inbreeding Avoidance Influences the Viability of Reintroduced Populations of African Wild Dogs (Lycaon pictus)

The conservation of many fragmented and small populations of endangered African wild dogs (Lycaon pictus) relies on understanding the natural processes affecting genetic diversity, demographics, and future viability. We used extensive behavioural, life-history, and genetic data from reintroduced African wild dogs in South Africa to (1) test for inbreeding avoidance via mate selection and (2) model the potential consequences of avoidance on population persistence. Results suggested that wild dogs avoided mating with kin. Inbreeding was rare in natal packs, after reproductive vacancies, and between sibling cohorts (observed on 0.8%, 12.5%, and 3.8% of occasions, respectively). Only one of the six (16.7%) breeding pairs confirmed as third-order (or closer) kin consisted of animals that were familiar with each other, while no other paired individuals had any prior association. Computer-simulated populations allowed to experience inbreeding had only a 1.6% probability of extinction within 100 years, whereas all populations avoiding incestuous matings became extinct due to the absence of unrelated mates. Populations that avoided mating with first-order relatives became extinct after 63 years compared with persistence of 37 and 19 years for those also prevented from second-order and third-order matings, respectively. Although stronger inbreeding avoidance maintains significantly more genetic variation, our results demonstrate the potentially severe demographic impacts of reduced numbers of suitable mates on the future viability of small, isolated wild dog populations. The rapid rate of population decline suggests that extinction may occur before inbreeding depression is observed

Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation

Purpose: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO. Methods: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms. Results: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred. Conclusions: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes

Protein Arrays: Issues to Be Addressed

Protein arrays are fast becoming established as a means to monitor protein expression levels and investigate protein interactions and function. They present particular technical demands that will need to be solved in order to achieve the maximum capability of efficient and sensitive protein analysis in the high throughput setting of functional genomics. The following resumé of some major issues around this new technology was made as the chairperson’s introduction to the workshop session on peptide and protein chips

Irreversible impacts of heat on the emissions of monoterpenes, sesquiterpenes, phenolic BVOC and green leaf volatiles from several tree species

Climate change will induce extended heat waves to parts of the vegetation more frequently. High temperatures may act as stress (thermal stress) on plants changing emissions of biogenic volatile organic compounds (BVOCs). As BVOCs impact the atmospheric oxidation cycle and aerosol formation, it is important to explore possible alterations of BVOC emissions under high temperature conditions. Applying heat to European beech, Palestine oak, Scots pine, and Norway spruce in a laboratory setup either caused the well-known exponential increases of BVOC emissions or induced irreversible changes of BVOC emissions. Considering only irreversible changes of BVOC emissions as stress impacts, we found that high temperatures decreased the &lt;i&gt;de novo&lt;/i&gt; emissions of monoterpenes, sesquiterpenes and phenolic BVOC. This behaviour was independent of the tree species and whether the &lt;i&gt;de novo&lt;/i&gt; emissions were constitutive or induced by biotic stress. &lt;br&gt;&lt;br&gt; In contrast, application of thermal stress to conifers amplified the release of monoterpenes stored in resin ducts of conifers and induced emissions of green leaf volatiles. In particular during insect attack on conifers, the plants showed &lt;i&gt;de novo&lt;/i&gt; emissions of sesquiterpenes and phenolic BVOCs, which exceeded constitutive monoterpene emissions from pools. The heat-induced decrease of &lt;i&gt;de novo&lt;/i&gt; emissions was larger than the increased monoterpene release caused by damage of resin ducts. For insect-infested conifers the net effect of thermal stress on BVOC emissions could be an overall decrease. &lt;br&gt;&lt;br&gt; Global change-induced heat waves may put hard thermal stress on plants. If so, we project that BVOC emissions increase is more than predicted by models only in areas predominantly covered with conifers that do not emit high amounts of sesquiterpenes and phenolic BVOCs. Otherwise overall effects of high temperature stress will be lower increases of BVOC emissions than predicted by algorithms that do not consider stress impacts