Masked priming and ERPs dissociate maturation of orthographic and semantic components of visual word recognition in children

This study examined the time-course of reading single words in children and adults using masked repetition priming and the recording of event-related potentials. The N250 and N400 repetition priming effects were used to characterize form- and meaning-level processing, respectively. Children had larger amplitude N250 effects than adults for both shorter and longer duration primes. Children did not differ from adults on the N400 effect. The difference on the N250 suggests that automaticity for form processing is still maturing in children relative to adults, while the lack of differentiation on the N400 effect suggests that meaning processing is relatively mature by late childhood. The overall similarity in the children's repetition priming effects to adults' effects is in line with theories of reading acquisition, according to which children rapidly transition to an orthographic strategy for fast access to semantic information from print.Ellison Medical FoundationF32HD06118

Quantifying the checks and balances of collaborative governance systems for adaptive carnivore management

Recovering or threatened carnivore populations are often harvested to minimise their impact on human activities, such as livestock farming or game hunting. Increasingly, harvest quota decisions involve a set of scientific, administrative and political institutions operating at national and sub-national levels whose interactions and collective decision-making aim to increase the legitimacy of management and ensure population targets are met. In practice, however, assessments of how quota decisions change between these different actors and what consequences these changes have on population trends are rare. We combine a state-space population modelling approach with an analysis of quota decisions taken at both regional and national levels between 2007 and 2018 to build a set of decision-making models that together predict annual harvest quota values for Eurasian lynx (Lynx lynx) in Norway. We reveal a tendency for administrative decision-makers to compensate for consistent quota increases by political actors, particularly when the lynx population size estimate is above the regional target. Using population forecasts based on the ensemble of decision-making models, we show that such buffering of political biases ensures lynx population size remains close to regional and national targets in the long term. Our results go beyond the usual qualitative assessment of collaborative governance systems for carnivore management, revealing a system of checks and balances that, in the case of lynx in Norway, ensures both multi-stakeholder participation and sustainable harvest quotas. Nevertheless, we highlight important inter-regional differences in decision-making and population forecasts, the socio-ecological drivers of which need to be better understood to prevent future population declines. Synthesis and applications. Our work analyses the sequence of decisions leading to yearly quotas for lynx harvest in Norway, highlighting the collaborative and structural processes that together shape harvest sustainability. In doing so, we provide a predictive framework to evaluate participatory decision-making processes in wildlife management, paving the way for scientists and decision-makers to collaborate more widely in identifying where decision biases might lie and how institutional arrangements can be optimised to minimise them. We emphasise, however, that this is only possible if wildlife management decisions are documented and transparent

Measuring disease-specific quality of life in rare populations: a practical approach to cross-cultural translation

<p>Abstract</p> <p>Background</p> <p>Disease-specific quality of life (QoL) measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder.</p> <p>Procedure</p> <p>A measurement study was conducted in the United Kingdom (UK), France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries.</p> <p>Results</p> <p>This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT), were performed in children with immune thrombocytopenic purpura (ITP). The KIT was translated from North American English into UK English, French, German, and Spanish.</p> <p>Conclusion</p> <p>This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.</p

Quantifying the checks and balances of collaborative governance systems for adaptive carnivore management

1. Recovering or threatened carnivore populations are often harvested to minimise their impact on human activities, such as livestock farming or game hunting. Increasingly, harvest quota decisions involve a set of scientific, administrative and political institutions operating at national and sub-national levels whose interactions and collective decision-making aim to increase the legitimacy of management and ensure population targets are met. In practice, however, assessments of how quota decisions change between these different actors and what consequences these changes have on population trends are rare. 2. We combine a state-space population modelling approach with an analysis of quota decisions taken at both regional and national levels between 2007 and 2018 to build a set of decision-making models that together predict annual harvest quota values for Eurasian lynx (Lynx lynx) in Norway. 3. We reveal a tendency for administrative decision-makers to compensate for consistent quota increases by political actors, particularly when the lynx population size estimate is above the regional target. Using population forecasts based on the ensemble of decision-making models, we show that such buffering of political biases ensures lynx population size remains close to regional and national targets in the long term. 4. Our results go beyond the usual qualitative assessment of collaborative governance systems for carnivore management, revealing a system of checks and balances that, in the case of lynx in Norway, ensures both multi-stakeholder participation and sustainable harvest quotas. Nevertheless, we highlight important inter-regional differences in decision-making and population forecasts, the socio-ecological drivers of which need to be better understood to prevent future population declines. 5. Synthesis and applications. Our work analyses the sequence of decisions leading to yearly quotas for lynx harvest in Norway, highlighting the collaborative and structural processes that together shape harvest sustainability. In doing so, we provide a predictive framework to evaluate participatory decision-making processes in wildlife management, paving the way for scientists and decision-makers to collaborate more widely in identifying where decision biases might lie and how institutional arrangements can be optimised to minimise them. We emphasise, however, that this is only possible if wildlife management decisions are documented and transparent

An analysis of returned medicines in primary care

Objective: The number of pharmaceutical items issued on prescription is continually rising and contributing to spiralling healthcare costs. Although there is some data highlighting the quantity, in terms of weight of medicines returned specifically to community pharmacies, little is known about the specific details of such returns or other destinations for wasted medications. This pilot study has been designed to investigate the types and amounts of medicines returned to both general practices (GPs) and associated local community pharmacies determining the reasons why these medicines have been returned. Method: The study was conducted in eight community pharmacies and five GP surgeries within East Birmingham over a 4-week period. Main outcome Measure: Reason for return and details of returned medication. Results: A total of 114 returns were made during the study: 24 (21.1) to GP surgeries and 90 (78.9) to community pharmacies. The total returns comprised 340 items, of which 42 (12.4) were returned to GPs and 298 (87.6) to pharmacies, with the mean number of items per return being 1.8 and 3.3, respectively. Half of the returns in the study were attributed to the doctor changing or stopping the medicine; 23.7 of returns were recorded as excess supplies or clearout often associated with patients' death and 3.5 of returns were related to adverse drug reactions. Cardiovascular drugs were most commonly returned, amounting to 28.5 of the total drugs returned during the study. Conclusions: The results from this pilot study indicate that unused medicines impose a significant financial burden on the National Health Service as well as a social burden on the United Kingdom population. Further studies are examining the precise nature of returned medicines and possible solutions to these issues. © Springer 2005

Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem

Transcription activation by the siderophore sensor Btr is mediated by ligand-dependent stimulation of promoter clearance

Bacterial transcription factors often function as DNA-binding proteins that selectively activate or repress promoters, although the biochemical mechanisms vary. In most well-understood examples, activators function by either increasing the affinity of RNA polymerase (RNAP) for the target promoter, or by increasing the isomerization of the initial closed complex to the open complex. We report that Bacillus subtilis Btr, a member of the AraC family of activators, functions principally as a ligand-dependent activator of promoter clearance. In the presence of its co-activator, the siderophore bacillibactin (BB), the Btr:BB complex enhances productive transcription, while having only modest effects on either RNAP promoter association or the production of abortive transcripts. Btr binds to two direct repeat sequences adjacent to the −35 region; recognition of the downstream motif is most important for establishing a productive interaction between the Btr:BB complex and RNAP. The resulting Btr:BB dependent increase in transcription enables the production of the ferric-BB importer to be activated by the presence of its cognate substrate