Building metamemorial knowledge over time: insights from eye tracking about the bases of feeling-of-knowing and confidence judgments

Metamemory processes depend on different factors across the learning and memory time-scale. In the laboratory, subjects are often asked to make prospective feeling-of-knowing (FOK) judgments about target retrievability, or are asked to make retrospective confidence judgments (RCJs) about the retrieved target. We examined distinct and shared contributors to metamemory judgments, and how they were built over time. Eye movements were monitored during a face-scene associative memory task. At test, participants viewed a studied scene, then rated their FOK that they would remember the associated face. This was followed by a forced choice recognition test and RCJs. FOK judgments were less accurate than RCJ judgments, showing that the addition of mnemonic experience can increase metacognitive accuracy over time. However, there was also evidence that the given FOK rating influenced RCJs. Turning to eye movements, initial analyses showed that higher cue fluency was related to both higher FOKs and higher RCJs. However, further analyses revealed that the effects of the scene cue on RCJs were mediated by FOKs. Turning to the target, increased viewing time and faster viewing of the correct associate related to higher FOKs, consistent with the idea that target accessibility is a basis of FOKs. In contrast, the amount of viewing directed to the chosen face, regardless of whether it was correct, predicted higher RCJs, suggesting that choice experience is a significant contributor RCJs. We also examined covariates of the change in RCJ rating from the FOK rating, and showed that increased and faster viewing of the chosen face predicted raising one’s confidence above one’s FOK. Taken together these results suggest that metamemory judgments should not be thought of only as distinct subjective experiences, but complex processes that interact and evolve as new psychological bases for subjective experience become available

Building Metamemorial Knowledge over Time: Insights from Eye Tracking about The Bases of Feeling-of-knowing and Confidence Judgements

Metamemory processes depend on different factors across the learning and memory time-scale. In the laboratory, subjects are often asked to make prospective feeling-of-knowing (FOK) judgments about target retrievability, or are asked to make retrospective confidence judgments (RCJs) about the retrieved target. We examined distinct and shared contributors to metamemory judgments, and how they were built over time. Eye movements were monitored during a face-scene associative memory task. At test, participants viewed a studied scene, then rated their FOK that they would remember the associated face. This was followed by a forced choice recognition test and RCJs. FOK judgments were less accurate than RCJ judgments, showing that the addition of mnemonic experience can increase metacognitive accuracy over time. However, there was also evidence that the given FOK rating influenced RCJs. Turning to eye movements, initial analyses showed that higher cue fluency was related to both higher FOKs and higher RCJs. However, further analyses revealed that the effects of the scene cue on RCJs were mediated by FOKs. Turning to the target, increased viewing time and faster viewing of the correct associate related to higher FOKs, consistent with the idea that target accessibility is a basis of FOKs. In contrast, the amount of viewing directed to the chosen face, regardless of whether it was correct, predicted higher RCJs, suggesting that choice experience is a significant contributor RCJs. We also examined covariates of the change in RCJ rating from the FOK rating, and showed that increased and faster viewing of the chosen face predicted raising one’s confidence above one’s FOK. Taken together these results suggest that metamemory judgments should not be thought of only as distinct subjective experiences, but complex processes that interact and evolve as new psychological bases for subjective experience become available

Dissociating Confidence and Accuracy: Functional Magnetic Resonance Imaging Shows Origins of the Subjective Memory Experience

Successful memory typically implies both objective accuracy and subjective confidence, but there are instances when confidence and accuracy diverge. This dissociation suggests that there may be distinct neural patterns of activation related to confidence and accuracy. We used event-related functional magnetic resonance imaging to study the encoding of novel face–name associations, assessed with a postscan memory test that included objective measures of accuracy and subjective measures of confidence. We showed specific neural activity in the left inferior prefrontal cortex associated with trials when subjects expressed high confidence that they had chosen the correct name for the face and made a correct identification. Moreover, we found that this region was also associated with imparting high confidence when subjects chose the incorrect name. However, medial temporal lobe regions showed activity only for high-confidence correct trials. Many functional magnetic resonance imaging studies have shown that the medial temporal lobe and left prefrontal regions are particularly important for the successful formation of memories by using a combination of subjective and objective measures. Our findings suggest that these regions may be differentially involved in the objective and subjective components of memory and that the origins of confidence–accuracy dissociations may be related to incomplete activation of the neural pattern seen in successful encoding. These findings may also aid understanding of eyewitness misidentifications and memory distortions.Psycholog

An inventory of supranational antimicrobial resistance surveillance networks involving low- and middle-income countries since 2000.

Low- and middle-income countries (LMICs) shoulder the bulk of the global burden of infectious diseases and drug resistance. We searched for supranational networks performing antimicrobial resistance (AMR) surveillance in LMICs and assessed their organization, methodology, impacts and challenges. Since 2000, 72 supranational networks for AMR surveillance in bacteria, fungi, HIV, TB and malaria have been created that have involved LMICs, of which 34 are ongoing. The median (range) duration of the networks was 6 years (1-70) and the number of LMICs included was 8 (1-67). Networks were categorized as WHO/governmental (n = 26), academic (n = 24) or pharma initiated (n = 22). Funding sources varied, with 30 networks receiving public or WHO funding, 25 corporate, 13 trust or foundation, and 4 funded from more than one source. The leading global programmes for drug resistance surveillance in TB, malaria and HIV gather data in LMICs through periodic active surveillance efforts or combined active and passive approaches. The biggest challenges faced by these networks has been achieving high coverage across LMICs and complying with the recommended frequency of reporting. Obtaining high quality, representative surveillance data in LMICs is challenging. Antibiotic resistance surveillance requires a level of laboratory infrastructure and training that is not widely available in LMICs. The nascent Global Antimicrobial Resistance Surveillance System (GLASS) aims to build up passive surveillance in all member states. Past experience suggests complementary active approaches may be needed in many LMICs if representative, clinically relevant, meaningful data are to be obtained. Maintaining an up-to-date registry of networks would promote a more coordinated approach to surveillance

Molecular characterisation of β-globin gene mutations in Penang and Kedah, Malaysia

Introduction: Beta-thalassaemia is an autosomal recessive disorder and it is a public health problem in the Malaysian Malays and Chinese. This disorder mainly results from point mutations, small insertion or deletions in the β-globin gene complex. Beta-thalassaemia major patients require life-long monthly blood transfusions and iron-chelation therapies to sustain their lives. Mutation characterisation is necessary for affected couples at risk of having a β-thalassaemia major child. Objective: 1. To develop the TaqMan genotyping platform as a time- and cost-effective approach for characterisation of β-globin gene mutations. 2. To characterise the mutations using the developed assays in transfusion-dependent patients in Penang and Kedah. Methods: Ten sets of primers and TaqMan probes were designed to identify the common mutations in Malaysian Malays and Chinese: −28 (A→G), CD17 (A→T), CD19 (A→G), HbE (G→A), IVS1-1 (G→T), IVS1-5 (G→C), CD 41/42 (-CTTT), CD71/72 (+A), IVS2-654 (C→T) and Poly A (AATAAAHAATAGA). Another 7 sets of TaqMan genotyping assays were designed to identify the rare mutations in Malays and Chinese: −29 (A→G), Cap (+1) (A→C), CD8/9 (+G), CD16 (-C), CD27/28 (+C), IVS1-1 (G→A) and CD43 (G→T). The developed assays were used to screen 54 and 62 transfusion-dependent patients in Penang and Kedah respectively. Results & Discussion: The developed assays detected 92.9% of mutations in the β-thalassaemia major patients. The remaining mutations were detected by ARMS, gap-PCR and DNA sequencing. The most common mutation in β-thalassaemia major patients in Penang is CD41/42 with a frequency of 20.9%. The most common mutation in β-thalassaemia major patients in Kedah is HbE with a frequency of 30.8%. Conclusion: The simplicity and reproducibility of the TaqMan genotyping assays enable rapid and cost-effective analysis of the β-globin gene mutations in Malaysia

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity

Theoretical studies of the historical development of the accounting discipline: a review and evidence

Many existing studies of the development of accounting thought have either been atheoretical or have adopted Kuhn's model of scientific growth. The limitations of this 35-year-old model are discussed. Four different general neo-Kuhnian models of scholarly knowledge development are reviewed and compared with reference to an analytical matrix. The models are found to be mutually consistent, with each focusing on a different aspect of development. A composite model is proposed. Based on a hand-crafted database, author co-citation analysis is used to map empirically the entire literature structure of the accounting discipline during two consecutive time periods, 1972–81 and 1982–90. The changing structure of the accounting literature is interpreted using the proposed composite model of scholarly knowledge development

Assessing dysphagia via telerehabilitation: patient perceptions and satisfaction

To gain insight into factors which may infl uence future acceptance of dysphagia management via telerehabilitation, patients’ perceptions were examined before and after a telerehabilitation assessment session. Forty adult patients with dysphagia(M = 66 years, SD = 16.25) completed pre- and post-session questionnaires which consisted of 14 matched questions worded to suit pre- and post-conditions. Questions explored comfort with the use of telerehabilitation, satisfaction with audio and video quality, benefi ts of telerehabilitation assessments and patients’ preferred assessment modality. Questions were rated on a 5-point scale (1 = strongly disagree, 3 = unsure, 5 = strongly agree). Patients’ comfort with assessment via telerehabilitation was high in over 80% of the group both pre- and post-assessment. Pre-assessment, patients were unsure what to expect with the auditory and visual aspects of the videoconference, however there were signifi cant positive changes reported post-experience. In relation to perceived benefits of telerehabilitation services in general, most patients believed in the value of telerehabilitation and post-assessment this increased to 90 – 100% agreement. Although 92% felt they would be comfortable receiving services via telerehabilitation, 45% of patients indicated ultimate preference for a traditional faceto-face assessment. The data highlight that patients are interested in and willing to receive services via telerehabilitation; however, any concerns should be addressed pre-assessment

Endosomal MR1 Trafficking Plays a Key Role in Presentation of Mycobacterium tuberculosis Ligands to MAIT Cells

Mucosal-Associated Invariant T (MAIT) cells, present in high frequency in airway and other mucosal tissues, have Th1 effector capacity positioning them to play a critical role in the early immune response to intracellular pathogens, including Mycobacterium tuberculosis (Mtb). MR1 is a highly conserved Class I-like molecule that presents vitamin B metabolites to MAIT cells. The mechanisms for loading these ubiquitous small molecules are likely to be tightly regulated to prevent inappropriate MAIT cell activation. To define the intracellular localization of MR1, we analyzed the distribution of an MR1-GFP fusion protein in antigen presenting cells. We found that MR1 localized to endosomes and was translocated to the cell surface upon addition of 6-formyl pterin (6-FP). To understand the mechanisms by which MR1 antigens are presented, we used a lentiviral shRNA screen to identify trafficking molecules that are required for the presentation of Mtb antigen to HLA-diverse T cells. We identified Stx18, VAMP4, and Rab6 as trafficking molecules regulating MR1-dependent MAIT cell recognition of Mtb-infected cells. Stx18 but not VAMP4 or Rab6 knockdown also resulted in decreased 6-FP-dependent surface translocation of MR1 suggesting distinct pathways for loading of exogenous ligands and intracellular mycobacterially-derived ligands. We postulate that endosome-mediated trafficking of MR1 allows for selective sampling of the intracellular environment.Career Development Award: (#IK2 CX000538); U.S. Department of Veterans Affairs Clinical Sciences Research and Development Program (MJH); U.S.Department of Veterans Affairs Biomedical Laboratory Research and Development Program (DML) Merit Award: (#I01 BX000533); American Lung Association: (RT-350058)

ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest