The effect of apolipoprotein E genotype on spatial processing in humans: A meta-analysis and systematic review.

The ε4 allele of the apolipoprotein E (APOE4) gene is an established risk factor for Alzheimer's disease but its impact on cognition in healthy adults across the lifespan is unclear. One cognitive domain that is affected early in the course of Alzheimer's disease is spatial cognition, yet the evidence for APOE-related changes in spatial cognition is mixed. In this meta-analysis we assessed the impact of carrying the APOE4 allele on five subdomains of spatial cognition across the lifespan. We included studies of healthy human participants where an APOE4-carrier group (heterozygous or homozygous) could be compared to a homozygous group of APOE3-carriers. We identified 156 studies in total from three databases (Pubmed, Scopus and Web of Science) as well as through searching cited literature and contacting authors for unpublished data. 122 studies involving 32,547 participants were included in a meta-analysis, and the remaining studies are included in a descriptive review. APOE4 carriers scored significantly lower than APOE3 carriers (θˆ = -.08 [-.14, -.02]) on tests of spatial long-term memory; this effect was very small and was not modulated by age. On other subdomains of spatial cognition (spatial construction, spatial working memory, spatial reasoning, navigation) there were no effects of genotype. Overall, our results demonstrate that the APOE4 allele exerts little influence on spatial cognitive abilities in healthy adults.

Clinician and parent views on urine collection in precontinent children in the UK: a qualitative interview study.

OBJECTIVE: To explore the experiences of healthcare professionals (HCPs) and parents of urine collection methods, to identify barriers to successful sampling and what could improve the process. DESIGN: Qualitative research, using individual semistructured interviews with HCPs and parents. The interviews were audiorecorded, transcribed and thematically analysed. SETTING: UK-based HCPs from primary and secondary care settings and parents with experience with urine collection in primary and/or secondary care settings. PARTICIPANTS: HCPs who were involved in aiding, supervising or ordering urine samples. Parents who had experience with urine collection in at least one precontinent child. RESULTS: 13 HCPs and 16 parents were interviewed. 2 participating HCPs were general practitioners (GPs), 11 worked in paediatric secondary care settings (8 were nurses and 3 were doctors). Two parents had children with underlying conditions where frequent urine collection was required to rule out infections.HCPs and parents reported that there were no straightforward methods of urine collection for precontinent children. Each method-'clean catch', urine bag and urine pad-had limitations and problems with usage. 'Clean catch', regarded as the gold standard by HCPs with a lower risk of contamination, often proved difficult for parents to achieve. Other methods had elevated risk of contamination but were more acceptable to parents because they were less challenging. Many of the parents expressed the need for more information about urine collection. CONCLUSIONS: Current methods of urine collection are challenging to use and may be prone to contamination. A new device is required to assist with urine collection in precontinent children, to simplify and reduce the stress of the situation for those involved. Parents are key partners in the process of urine collection with young children. Meeting their expressed need for more information could be an important way to achieve better-quality samples while awaiting a new device.

Infections diagnosed in children and young people screened for malaria in UK emergency departments: a retrospective multi-centre study.

BACKGROUND: Data on imported infections in children and young people (CYP) are sparse. AIMS: To describe imported infections in CYP arriving from malaria-endemic areas and presenting to UK emergency departments (ED) who were screened for malaria. METHODS: This is a retrospective, multi-centre, observational study nested in a diagnostic accuracy study for malaria rapid diagnostic tests. Any CYP < 16 years presenting to a participating ED with a history of fever and travel to a malaria-endemic area between 1 January 2016 and 31 December 2017 and who had a malaria screen as a part of standard care were included. Geographical risk was calculated for the most common tropical infections. RESULTS: Of the 1414 CYP screened for malaria, 44.0% (n = 622) arrived from South Asia and 33.3% (n = 471) from sub-Saharan Africa. Half (50.0%) had infections common in both tropical and non-tropical settings such as viral upper respiratory tract infection (URTI); 21.0% of infections were coded as tropical if gastro-enteritis is included, with a total of 4.2% (60) cases of malaria. CYP diagnosed with malaria were 7.44 times more likely to have arrived from sub-Saharan Africa than from South Asia (OR 7.44, 3.78-16.41). CONCLUSION: A fifth of CYP presenting to participating UK EDs with fever and a history of travel to a malaria-endemic area and who were screened for malaria had a tropical infection if diarrhoea is included. A third of CYP had no diagnosis. CYP arriving from sub-Saharan Africa had the greatest risk of malaria.Abbreviations: CYP: children and young people; ED: emergency department; PERUKI: Paediatric Emergency Research in the UK and Ireland; RDT: rapid diagnostic test; VFR: visiting friends and relatives.

False memories for ending of events.

Memories are not perfect recordings of the past and can be subject to systematic biases. Memory distortions are often caused by our experience of what typically happens in a given situation. However, it is unclear whether memory for events is biased by the knowledge that events usually have a predictable structure (a beginning, middle, and an end). Using video clips of everyday situations, we tested how interrupting events at unexpected time points affects memory of how those events ended. In four free recall experiments (1, 2, 4, and 5), we found that interrupting clips just before a salient piece of action was completed, resulted in the false recall of details about how the clip might have ended. We refer to this as "event extension." On the other hand, interrupting clips just after one scene had ended and a new scene started, resulted in omissions of details about the true ending of the clip (Experiments 4 and 5). We found that these effects were present, albeit attenuated, when testing memory shortly after watching the video clips compared to a week later (Experiments 5a and 5b). The event extension effect was not present when memory was tested with a recognition paradigm (Experiment 3). Overall, we conclude that when people watch videos that violate their expectations of typical event structure, they show a bias to later recall the videos as if they had ended at a predictable event boundary, exhibiting event extension or the omission of details depending on where the original video was interrupted. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Diagnostic Accuracy Study to Evaluate Standard Rapid Diagnostic Test (RDT) Alone to Safely Rule Out Imported Malaria in Children Presenting to UK Emergency Departments.

BACKGROUND: Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs). METHODS: UK-based, multi-center, retrospective, diagnostic accuracy study. Included: any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341. RESULTS: There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2-9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5-98.7%), specificity 99.4% (95% CI 98.9-99.7%), positive predictive value 84.6% (95% CI 71.9-93.1%) and negative predictive value 99.8% (95% CI 99.4-100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3-100%), specificity 98.8% (98.1-99.3%), positive predictive value 69.2% (54.9-81.2%, n = 46/52) and negative predictive value 100% (99.7-100%, n = 1,362/1,362). CONCLUSIONS: RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria.

Hippocampal and medial prefrontal cortices encode structural task representations following progressive and interleaved training schedules.

Memory generalisations may be underpinned by either encoding- or retrieval-based generalisation mechanisms and different training schedules may bias some learners to favour one of these mechanisms over the other. We used a transitive inference task to investigate whether generalisation is influenced by progressive vs randomly interleaved training, and overnight consolidation. On consecutive days, participants learnt pairwise discriminations from two transitive hierarchies before being tested during fMRI. Inference performance was consistently better following progressive training, and for pairs further apart in the transitive hierarchy. BOLD pattern similarity correlated with hierarchical distances in the left hippocampus (HIP) and medial prefrontal cortex (MPFC) following both training schedules. These results are consistent with the use of structural representations that directly encode hierarchical relationships between task features. However, such effects were only observed in the MPFC for recently learnt relationships. Furthermore, the MPFC appeared to maintain structural representations in participants who performed at chance on the inference task. We conclude that humans preferentially employ encoding-based mechanisms to store map-like relational codes that can be used for memory generalisation. These codes are expressed in the HIP and MPFC following both progressive and interleaved training but are not sufficient for accurate inference.

The Importance of Semantic Network Brain Regions in Integrating Prior Knowledge with an Ongoing Dialogue.

To understand a dialogue, we need to know the topics that are being discussed. This enables us to integrate our knowledge of what was said previously to interpret the current dialogue. This study involved a large-scale behavioral experiment conducted online and a separate fMRI experiment, both testing human participants. In both, we selectively manipulated knowledge about the narrative content of dialogues presented in short videos. The clips were scenes from situation comedies that were split into two parts. The speech in the part 1 clips could either be presented normally or spectrally rotated to render it unintelligible. The part 2 clips that concluded the scenes were always presented normally. The behavioral experiment showed that knowledge of the preceding narrative boosted memory for the part 2 clips as well as increased the intersubject semantic similarity of recalled descriptions of the dialogues. The fMRI experiment replicated the finding that prior knowledge improved memory for the conclusions of the dialogues. Furthermore, prior knowledge strengthened temporal intersubject correlations in brain regions including the left angular gyrus and inferior frontal gyrus. Together, these findings show that (1) prior knowledge constrains the interpretation of a dialogue to be more similar across individuals; and (2), consistent with this, the activation of brain regions involved in semantic control processing is also more similar between individuals who share the same prior knowledge. Processing in these regions likely supports the activation and integration of prior knowledge, which helps people to better understand and remember dialogues as they unfold.

Point-of-care diagnostic technology in paediatric ambulatory care: a qualitative interview study of English clinicians and stakeholders.

Point-of-care (POC) tests have the potential to improve paediatric healthcare. However, both the development and evaluation of POC technology have almost solely been focused on adults. We aimed to explore frontline clinicians' and stakeholders' current experience of POC diagnostic technology in children in England; and to identify areas of unmet need. DESIGN, SETTING AND PARTICIPANTS: Qualitative semistructured telephone interviews were carried out with purposively sampled participants from clinical paediatric ambulatory care and charity, industry and policymaking stakeholders. The interviews were audio-recorded, transcribed and analysed thematically. RESULTS: We interviewed 19 clinicians and 8 stakeholders. The main perceived benefits of POC tests and technologies were that they aided early decision-making and could be convenient and empowering when used independently by patients and families. Clinicians and stakeholders wanted more POC tests to be available for use in clinical practice. Most recognised that play and reward are important components of successful POC tests for children. Clinicians wanted tests to give them answers, which would result in a change in their clinical management. Detecting acute serious illness, notably distinguishing viral and bacterial infection, was perceived to be an area where tests could add value. POC tests were thought to be particularly useful for children presenting atypically, where diagnosis was more challenging, such as those less able to communicate, and for rare serious diseases. Many participants felt they could be useful in managing chronic disease. CONCLUSIONS: This exploratory study found that clinicians and stakeholders supported the use of diagnostic POC technology in paediatric ambulatory care settings in England. Some existing tests are not fit for purpose and could be refined. Industry should be encouraged to develop new child-friendly tests tackling areas of unmet need, guided by the preferred characteristics of those working on the ground.

The Neural Representation of Events Is Dominated by Elements that Are Most Reliably Present.

An episodic memory is specific to an event that occurred at a particular time and place. However, the elements that constitute the event-the location, the people present, and their actions and goals-might be shared with numerous other similar events. Does the brain preferentially represent certain elements of a remembered event? If so, which elements dominate its neural representation: those that are shared across similar events, or the novel elements that define a specific event? We addressed these questions by using a novel experimental paradigm combined with fMRI. Multiple events were created involving conversations between two individuals using the format of a television chat show. Chat show "hosts" occurred repeatedly across multiple events, whereas the "guests" were unique to only one event. Before learning the conversations, participants were scanned while viewing images or names of the (famous) individuals to be used in the study to obtain person-specific activity patterns. After learning all the conversations over a week, participants were scanned for a second time while they recalled each event multiple times. We found that during recall, person-specific activity patterns within the posterior midline network were reinstated for the hosts of the shows but not the guests, and that reinstatement of the hosts was significantly stronger than the reinstatement of the guests. These findings demonstrate that it is the more generic, familiar, and predictable elements of an event that dominate its neural representation compared with the more idiosyncratic, event-defining, elements.

The First WHO International Standard for Adalimumab: Dual Role in Bioactivity and Therapeutic Drug Monitoring.

The expanded availability of adalimumab products continues to widen patient access and reduce costs with substantial benefit to healthcare systems. However, the long-term success of these medicines is highly dependent on maintaining consistency in quality, safety and efficacy while minimizing any risk of divergence during life-cycle management. In recognition of this need and demand from global manufacturers, the World Health Organization (WHO) Expert Committee on Biological standardization established the WHO 1st International standard (IS) for Adalimumab (coded 17/236) in October 2019 with a defined unitage ascribed to each of the individual bioactivities evaluated in the study namely, TNF-α binding, TNF-α neutralization, complement dependent cytotoxicity and antibody-dependent cellular cytotoxicity. For development of the IS, two candidate standards were manufactured as per WHO recommendations. Analysis of extensive datasets generated by testing of a common set of samples including the candidate standards by multiple stakeholders including regulatory agencies using their own qualified assays in a large international collaborative study showed comparable biological activity for the tested candidates for the different activities. Use of a common standard significantly decreased the variability of bioassays and improved agreement in potency estimates. Data from this study clearly supports the utility of the IS as an important tool for assuring analytical assay performance, for bioassay calibration and validation, for identifying and controlling changes in bioactivity during life-cycle management and for global harmonization of adalimumab products. In addition, in a separate multi-center study which included involvement of hospital and clinical diagnostic laboratories, the suitability of the adalimumab IS for therapeutic drug monitoring assays was examined by analysis of data from testing of a common blind coded panel of adalimumab spiked serum samples representative of the clinical scenario along with the IS and in-house standards in diverse immunoassays/platforms. Both commercially available and in-house assays that are routinely used for assessing adalimumab trough levels were included. Excellent agreement in estimates for adalimumab content in the spiked samples was observed regardless of the standard or the method with inter-laboratory variability also similar regardless of the standard employed. This data, for the first time, provides support for the extended applicability of the IS in assays in use for therapeutic drug monitoring based on the mass content of the IS. The adalimumab IS, in fulfilling clinical demand, can help toward standardizing and harmonizing clinical monitoring assays for informed clinical decisions and/or personalized treatment strategies for better patient outcomes. Collectively, a significant role for the adalimumab IS in assuring the quality, safety and efficacy of adalimumab products globally is envisaged.

Activation of Person Knowledge in Medial Prefrontal Cortex during the Encoding of New Lifelike Events.

Our knowledge about people can help us predict how they will behave in particular situations and interpret their actions. In this study, we investigated the cognitive and neural effects of person knowledge on the encoding and retrieval of novel life-like events. Healthy human participants learnt about two characters over a week by watching 6 episodes of one of two situation comedies, which were both centered on a young couple. In the scanner, they watched and then silently recalled 20 new scenes from both shows that were all set in unfamiliar locations: 10 from their trained show and 10 from the untrained show. After scanning, participants' recognition memory was better for scenes from the trained show. The functional magnetic resonance imaging (fMRI) patterns of brain activity when watching the videos were reinstated during recall, but this effect was not modulated by training. However, person knowledge boosted the similarity in fMRI patterns of activity in the medial prefrontal cortex (MPFC) when watching the new events involving familiar characters. Our findings identify a role for the MPFC in the representation of schematic person knowledge during the encoding of novel, lifelike events.

A Pragmatic Study to Evaluate the Use of a Rapid Diagnostic Test to Detect Group A Streptococcal Pharyngitis in Children With the Aim of Reducing Antibiotic Use in a UK Emergency Department.

OBJECTIVE: Sore throat is a common presentation to the children's emergency department (ED), and many patients are likely prescribed antibiotics unnecessarily. We aimed to reduce antibiotic prescribing for sore throat in our UK ED through use of an established scoring system combined with a rapid diagnostic test (RDT) to detect group A streptococcal (GAS) pharyngitis. METHODS: AB single-subject and diagnostic accuracy studies were used to measure both antibiotic prescribing rates over time and the performance of the McIsaac clinical score combined with RDT to screen for and treat GAS pharyngitis. All children between the age of 6 months and 16 years with symptoms of sore throat were eligible for inclusion. The study adhered to SQUIRE guidelines. RESULTS: During 2014 and 2016, antibiotic prescribing rates for 210 children at baseline (median age, 3 years) and 395 children during the intervention (median age, 2 years) were assessed. The baseline prescribing rate was 79%, whereas rates after intervention were 24% and 27%, respectively. The RDT had an acceptable false-negative rate of 7.9%, poor sensitivity of 64.3%, and a negative predictive value of 92.1% when compared with conventional throat culture. A McIsaac score of 3 or more had good sensitivity (92.11%) but very low specificity (12.62%) for predicting GAS infection. CONCLUSIONS: Despite poor RDT sensitivity and the McIsaac score's poor specificity in children, their use in combination decreased antibiotic prescribing rates in a children's ED setting.

Minocycline differentially modulates human spatial memory systems.

Microglia play a critical role in many processes fundamental to learning and memory in health and are implicated in Alzheimer's pathogenesis. Minocycline, a centrally-penetrant tetracycline antibiotic, inhibits microglial activation and enhances long-term potentiation, synaptic plasticity, neurogenesis and hippocampal-dependent spatial memory in rodents, leading to clinical trials in human neurodegenerative diseases. However, the effects of minocycline on human memory have not previously been investigated. Utilising a double-blind, randomised crossover study design, we recruited 20 healthy male participants (mean 24.6 ± 5.0 years) who were each tested in two experimental sessions: once after 3 days of Minocycline 150 mg (twice daily), and once 3 days of placebo (identical administration). During each session, all completed an fMRI task designed to tap boundary- and landmark-based navigation (thought to rely on hippocampal and striatal learning mechanisms respectively). Given the rodent literature, we hypothesised that minocycline would selectively modulate hippocampal learning. In line with this, minocycline biased use of boundary- compared to landmark-based information (t980 = 3.140, p = 0.002). However, though this marginally improved performance for boundary-based objects (t980 = 1.972, p = 0.049), it was outweighed by impaired landmark-based navigation (t980 = 6.374, p < 0.001) resulting in an overall performance decrease (t980 = 3.295, p = 0.001). Furthermore, against expectations, minocycline significantly reduced activity during memory encoding in the right caudate (t977 = 2.992, p = 0.003) and five other cortical regions, with no significant effect in the hippocampus. In summary, minocycline impaired human spatial memory performance, likely through disruption of striatal processing resulting in greater biasing towards reliance on boundary-based navigation.

Paediatric contacts with the UK out-of-hours primary care service and contact outcomes: a regional service evaluation.

BACKGROUND: Demand on hospital emergency departments for paediatric problems is increasing. However, the volume and nature of paediatric health demands placed on other parts of the urgent care system have not been explored. This understanding is an important first step in developing and improving out-of-hospital care. We aimed to describe the volume, nature, and outcomes of paediatric contacts with out-of-hours general practice (OOH GP). We performed a retrospective service evaluation using data from 12 months of paediatric patient contacts with the Oxfordshire OOH GP service. METHODS: A database of contacts with the Oxfordshire OOH GP service was created for a 12 month period from December 2014 to November 2015. Descriptive statistics were calculated using SPSS Version 25. RESULTS: 27,455 contacts were made by 18,987 individuals during a 12 month period. The majority of these were for children aged under 5. Over 70% of contacts were at the weekend. The peak contact period was between 18:30 and 21:30. Over 40% of contacts resulted in advice only (no onward referral, requirement for GP follow up, or prescription). 19.7% of contacts resulted in an antibiotic prescription, most commonly those linked with ear, chest, and throat infections. DISCUSSION: Paediatric contacts with the Oxfordshire OOH GP service were predominantly in younger age groups and in the evening, with 19.7% resulting in an antibiotic prescription. Almost half of the contacts had no follow up or prescription, suggesting non-prescribing health care professionals could be involved in providing care in OOH GP. Further research should consider how children and their parents can be best supported to optimise OOH consulting.

Not just little adults: preparing a children's emergency department for COVID-19.

COVID-19 presented unique challenges in preparing our stand-alone children's emergency department for the pandemic and has demonstrated well the paediatric adage, 'children aren't little adults'.

The brain regions supporting schema-related processing of people's identities.

Schematic knowledge about people helps us to understand their behaviour in novel situations. The ventromedial prefrontal cortex (vmPFC) and hippocampus play important, yet poorly understood, roles in schema-based processing. Here, we manipulated schematic knowledge by familiarizing participants over the course of a week to the two lead characters of one of two TV shows. Then during MRI scanning, they viewed pictures of all four characters and performed a recognition memory test afterwards. Memory was also tested for short videos. Schematic knowledge boosted performance on both memory tests. Whole-brain analyses revealed knowledge related activation increases in the vmPFC and retrosplenial cortex while a similar effect was identified in a hippocampal region-of-interest. Representational similarity analyses identified person-specific patterns of activity in the vmPFC but not hippocampus, but no effect of familiarization. Our findings suggest complementary roles for the vmPFC and hippocampus in processing schematic knowledge that was acquired in a naturalistic manner.

Predicting memory formation over multiple study episodes.

Repeated study typically improves episodic memory performance. Two different types of explanations of this phenomenon have been put forward: (1) reactivating the same representations strengthens and stabilizes memories, or (2) greater encoding variability benefits memory by promoting richer traces. The present experiment directly compared these predictions in a design with multiple repeated study episodes, allowing to dissociate memory for studied items and their context of study. Participants repeatedly encoded names of famous people four times, either in the same task, or in different tasks. During the test phase, an old/new judgment task was used to assess item memory, followed by a source memory judgment about the encoding task. Consistent with predictions from the encoding variability view, encoding stimulus in different contexts resulted in higher item memory. In contrast, consistent with the reactivation view, source memory performance was higher when participants encoded stimuli in the same task repeatedly. Taken together, our findings indicate that encoding variability benefits episodic memory, by increasing the number of items that are recalled. These benefits are however at the expenses of source recollection and memory for details, which are decreased, likely due to interference and generalization across contexts.

Effects of amnesia on processing in the hippocampus and default mode network during a naturalistic memory task: A case study.

Despite their severely impaired episodic memory, individuals with amnesia are able to comprehend ongoing events. Online representations of a current event are thought to be supported by a network of regions centred on the posterior midline cortex (PMC). By contrast, episodic memory is widely believed to be supported by interactions between the hippocampus and these cortical regions. In this MRI study, we investigated the encoding and retrieval of real life-like events (video clips) in a patient with severe amnesia likely resulting from a stroke to the right (and possibly the left) thalamus, and a group of 20 age-matched controls. Structural MRI revealed grey matter reductions in left hippocampus and left thalamus in comparison to controls. We first characterised the regions activated in the controls while they watched and retrieved the videos. There were no differences in activation between the patient and controls in any of the regions. We then identified a widespread network of brain regions, including the hippocampus, that were functionally connected with the PMC in controls. However, in the patient there was a specific reduction in functional connectivity between the PMC and a region of left hippocampus when both watching and attempting to retrieve the videos. A follow up analysis of the control group revealed that, when watching the videos, the functional connectivity between these two regions was correlated with memory performance. Taken together, these findings support the view that the interactions between the PMC and the hippocampus enable the encoding and retrieval of naturalistic events.

The processing of color preference in the brain.

Decades of research has established that humans have preferences for some colors (e.g., blue) and a dislike of others (e.g., dark chartreuse), with preference varying systematically with variation in hue (e.g., Hurlbert and Owen, 2015). Here, we used functional MRI to investigate why humans have likes and dislikes for simple patches of color, and to understand the neural basis of preference, aesthetics and value judgements more generally. We looked for correlations of a behavioural measure of color preference with the blood oxygen level-dependent (BOLD) response when participants performed an irrelevant orientation judgement task on colored squares. A whole brain analysis found a significant correlation between BOLD activity and color preference in the posterior midline cortex (PMC), centred on the precuneus but extending into the adjacent posterior cingulate and cuneus. These results demonstrate that brain activity is modulated by color preference, even when such preferences are irrelevant to the ongoing task the participants are engaged. They also suggest that color preferences automatically influence our processing of the visual world. Interestingly, the effect in the PMC overlaps with regions identified in neuroimaging studies of preference and value judgements of other types of stimuli. Therefore, our findings extends this literature to show that the PMC is related to automatic encoding of subjective value even for basic visual features such as color.

The first World Health Organization International Standard for infliximab products: A step towards maintaining harmonized biological activity.

Due to the increase in the number of infliximab products, the need for global harmonization of the bioactivity of this monoclonal antibody was recognized by the World Health Organization (WHO). In response, the National Institute for Biological Standards and Control (NIBSC) developed the first international standard (IS) for infliximab, which targets tumour necrosis factor (TNF). Each ampoule is assigned values of 500 IU of TNF neutralizing activity and 500 IU of binding activity. Two preparations of infliximab were formulated and lyophilized at NIBSC prior to evaluation in a collaborative study for their suitability to serve as an IS for the in vitro biological activity of infliximab. The study involved participants using in vitro cell-based bioassays (TNF neutralization, antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity) and binding assays. The results of this study showed that the candidate preparation, coded 16/170, is suitable as an IS for infliximab bioactivity. This infliximab IS from NIBSC, is intended to support in vitro bioassay calibration and validation by defining international units of bioactivity. The proposed unitages, however, are not intended to revise product labelling or dosing requirements, as any decisions regarding this relies solely with the regulatory authorities. Furthermore, the infliximab IS is not intended for determining the specific activity of products, nor to serve any regulatory role in defining biosimilarity. We briefly discuss the future use of WHO international standards in supporting the global harmonisation of biosimilar infliximab products.