343 research outputs found

    Different Definitions of the Non-recollection-based Response Option(s) Change how People use the “Remember” Response in the Remember/Know Paradigm

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    In the Remember/Know paradigm, a Know response can be defined to participants as a high-confidence state of certainty or as a low-confidence state based on a feeling of familiarity. To examine the effects of definition on use of responses, in two experiments definitions of Remember and Guess were kept constant but definitions of Know and/or Familiar were systematically varied to emphasize (a) a subjective experience of high-confidence-without-recollection, (b) a feeling of familiarity, (c) both of these subjective experiences combined within one response option, or (d) both of these experiences as separate response options. The confidence expressed in Know and/or Familiar definitions affected how participants used response options. Importantly this included use of the Remember response, which tended to be used more frequently when the non-recollection-based middle response option emphasized a feeling of familiarity rather than an experience of “just knowing.” The influence of the definitions on response patterns was greater for items that had undergone deep rather than shallow processing, and was greater when deep- and shallow-encoded items were mixed, rather than blocked, at test. Our findings fit with previous research suggesting that the mnemonic traces underlying subjective judgments are continuous and that the Remember/Know paradigm is not a pure measure of underlying processes. Findings also emphasize the importance of researchers publishing the exact definitions they have used to enable accurate comparisons across studies

    Trends in Weekly Reported Net use by Children During and after Rainy Season in Central Tanzania.

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    The use of long-lasting insecticidal nets (LLINs) is one of the principal interventions to prevent malaria in young children, reducing episodes of malaria by 50% and child deaths by one fifth. Prioritizing young children for net use is important to achieve mortality reductions, particularly during transmission seasons. Households were followed up weekly from January through June 2009 to track net use among children under seven under as well as caretakers. Net use rates for children and caretakers in net-owning households were calculated by dividing the number of person-weeks of net use by the number of person-weeks of follow-up. Use was stratified by age of the child or caretaker status. Determinants of ownership and of use were assessed using multivariate models. Overall, 60.1% of the households reported owning a bed net at least once during the study period. Among net owners, use rates remained high during and after the rainy season. Rates of use per person-week decreased as the age of the child rose from 0 to six years old; at ages 0-23 months and 24-35 months use rates per person-week were 0.93 and 0.92 respectively during the study period, while for children ages 3 and 4 use rates per person-week were 0.86 and 0.80. For children ages 5-6 person-week ratios dropped to 0.55. This represents an incidence rate ratio of 1.67 for children ages 0-23 months compared to children aged 5-6. Caretakers had use rates similar to those of children age 0-35 months. Having fewer children under age seven in the household also appeared to positively impact net use rates for individual children. In this area of Tanzania, net use is very high among net-owning households, with no variability either at the beginning or end of the rainy season high transmission period. The youngest children are prioritized for sleeping under the net and caretakers also have high rates of use. Given the high use rates, increasing the number of nets available in the household is likely to boost use rates by older children

    Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

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    Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

    Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

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    Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

    Autoimmune and autoinflammatory mechanisms in uveitis

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    The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

    Pandemic Preparedness in the Live Performing Arts: Lessons to Learn from COVID-19 in the G7 Countries: Project Report

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    This is the final versionThis report publishes the findings of the British Academy-funded Pandemic Preparedness: Lessons to Learn from Covid-19 across the G7 project. Between April 2023 - January 2024, a UK-led research team with Co-Investigators in the USA, Canada and Germany and Research Associates in France, Italy and Japan examined the lessons learned from the responses of the live performing arts sector and governments to COVID-19 in the G7 countries. We focused our attention on policy interventions by governments and funders alongside the individual responses by workers in the live performing arts as well as organisations and their audiences. We further considered the impact of the pandemic on digital modes of working and disseminating creative content; how the pandemic affected communities, places and how ‘cultural value’ is understood; and what the pandemic revealed about systems and structures in the sector. The aim was to support sector preparedness for future crises, whether caused by new pandemics, climate-related disasters, demographic changes, economic pressures or the impacts on the live performing arts of national and international politics. This full report consists of detailed literature reviews of how the pandemic affected the performing arts sector in the United Kingdom, the USA, Canada and Germany; it also contains shorter literature reviews which focus on France, Italy and Japan. This research underpins the policy recommendations which are published in separate reports.British Academ

    Risks and benefits of bisphosphonates

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    Bone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers due to the prevalence of these diseases. Bone metastases result in considerable morbidity and complex demands on health care resources, affecting quality of life and independence over years rather than months. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma as well as a wide range of solid tumours affecting bone by 30–50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain

    Development of Second-Generation VEGFR Tyrosine Kinase Inhibitors: Current Status

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    The vascular endothelial growth factor (VEGF) signaling pathway appears to be the dominant pathway involved in tumor angiogenesis, providing a rationale for targeting the VEGF receptors (VEGFR-1, -2, and -3) in the treatment of cancers. In particular, VEGF signaling is thought to be important in renal cell carcinoma (RCC) because of the deregulation of the pathway through nearly uniform loss of the von Hippel Lindau protein. The tyrosine kinase inhibitors (TKIs) sorafenib, sunitinib, and pazopanib are approved by the US Food and Drug Administration for the treatment of advanced RCC; however, these multitargeted agents inhibit a wide range of kinase targets in addition to the VEGFRs, resulting in a range of adverse effects unrelated to efficient VEGF blockade. This article reviews recent advances in the development of the second-generation VEGFR TKIs, including the more selective VEGFR TKIs tivozanib and axitinib, and focuses on the potential benefits of novel inhibitors with improved potency and selectivity
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