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

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Do concentration or activity of selenoproteins change in acute stroke patients? A systematic review and meta-analyses

IntroductionStroke is characterized by deleterious oxidative stress. Selenoprotein enzymes are essential endogenous antioxidants and detailed insight into their role after stroke could define new therapeutic treatments. This systematic review aims to elucidate how blood selenoprotein concentration and activity change in the acute phase of stroke.MethodsWe searched PubMed, EMBASE and Medline databases for studies measuring serial blood selenoprotein concentration or activity in acute stroke patients or in stroke patients compared to non-stroke controls. Meta-analyses of studies stratified by type of stroke, blood compartment and type of selenoprotein measurement were conducted.ResultsEighteen studies and data from 941 stroke patients and 708 non-stroke controls were included in this review. Glutathione peroxidase (GPx) was the only identified selenoprotein and its activity was most frequently measured. Results from 12 studies and 693 patients, showed that, compared to non-stroke controls, in acute ischaemic stroke patients GPx activity increased in haemolysate (standardised mean difference (SMD): 0.27, 95% CI 0.07 to 0.47) but decreased in plasma (mean difference (MD): -1.08 U/L, 95% CI -1.94 to -0.22) and serum (SMD: -0.54, 95% CI -0.91 to -0.17). From four identified studies in 106 acute haemorrhagic stroke patients, GPx activity decreased in haemolysate (SMD: -0.40, 95% CI - 0.68 to -0.13) and remained unchanged in plasma (MD: -0.10 U/L, 95% CI -0.81 to 0.61) and serum (MD: -5.00 U/mL, 95% CI -36.17 to 26.17) compared to non-stroke controls. Results from studies assessing GPx activity in the haemolysate compartment were inconsistent and characterized by high heterogeneity.ConclusionsOur results suggest a reduction of blood GPx activity in acute ischaemic stroke patients, a lack of evidence regarding a role for GPx in haemorrhagic stroke patients and insufficient evidence for other selenoproteins

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

Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al

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

Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation. Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation. Panellists independently completed a consensus survey of 57 questions, rating each on a 9-point Likert scale. Subsequently, panellists attended a consensus meeting to discuss survey outcomes and readjust scores independently if desired. Survey items with median scores ≥ 7 were considered ‘required/appropriate’, ≤ 3 ‘not required/inappropriate’, and 4–6 indicated ‘uncertainty remained’. Consensus was determined as ~ 70% participant agreement on whether the item was ‘required/appropriate’ or ‘not required/not appropriate’. Results: Consensus was achieved for 38 of 57 (67%) survey questions related to preclinical and clinical methodologies, and stakeholder engagement. For evaluating established radiotracers in new cancer types, in vitro and preclinical studies were considered unnecessary, clinical pharmacokinetic studies were considered appropriate, and clinical dosimetry and biodistribution studies were considered unnecessary, if sufficient previous data existed. There was ‘agreement without consensus’ that clinical repeatability and reproducibility studies are required while ‘uncertainty remained’ regarding the need for comparison studies. For novel radiotracers, in vitro and preclinical studies, such as dosimetry and/or biodistribution studies and tumour histological assessment were considered appropriate, as well as comprehensive clinical validation. Conversely, preclinical reproducibility studies were considered unnecessary and ‘uncertainties remained’ regarding preclinical pharmacokinetic and repeatability evaluation. Other consensus areas included standardisation of clinical study protocols, streamlined regulatory frameworks and patient and public involvement. While a centralised UK clinical imaging research infrastructure and open access federated data repository were considered necessary, there was ‘agreement without consensus’ regarding the requirement for a centralised UK preclinical imaging infrastructure. Conclusions: We provide consensus-based recommendations, emphasising streamlined methodologies and regulatory frameworks, together with active stakeholder engagement, for improving PET radiotracer standardisation, reproducibility and clinical implementation in oncology