Embedding post-doctoral clinical academic careers in practice: The St Bartholomew's Hospital model.

AIMS AND OBJECTIVES: In order to retain and develop pre-doctoral and doctoral staff, we sought to establish and implement a model for supporting postdoctoral clinical academic careers at our hospital. BACKGROUND: Doctorally-prepared nurses can raise clinical practice standards, but there is a deficit of career opportunities and post-doctoral positions. This will inevitably impact delivering the evidence for improving patient outcomes and service delivery. It is therefore imperative that post-doctoral nursing and allied professional post-doctoral clinical academic career opportunities are developed and embedded in practice. DESIGN: We describe the development and implementation of a model to provide and embed post-doctoral clinical academic roles at our hospital. METHODS: A multidisciplinary group devised the model which was approved by the Hospital Executive Board. RESULTS: The model includes having a bespoke plan for each individual, planning the post-doctoral role at time of PhD planning, providing 1 day a week protected research time for a minimum of 12 months after PhD completion, having an appropriate honorary academic contract at a partner University, and providing integrated clinical and academic supervision throughout. Other key components include senior clinical and Executive Board support and an existing vibrant research culture at our organisation. CONCLUSIONS: The St Bartholomew's Hospital model, focusing on individualised posts integrating clinical and academic roles to address service needs, offers a novel approach to supporting post-doctoral clinical academic careers in a clinical setting. RELEVANCE TO CLINICAL PRACTICE: Since doctorally-prepared nurses can raise clinical practice standards we developed a sustainable infrastructure to increase our postdoctoral nursing and allied professional workforce. This model could provide a framework for other hospitals to embed postdoctoral clinical academic careers in practice.

Duration of untreated eating disorder and relationship to outcomes: A systematic review of the literature.

OBJECTIVE: This systematic review assesses the average duration of untreated eating disorder (DUED) in help-seeking populations at the time of first eating disorder (ED) treatment and investigates the relationship between DUED and symptom severity/clinical outcomes. METHOD: PRISMA guidelines were followed throughout. Selected studies provided information on either: (i) length of DUED, (ii) components of DUED, (iii) cross-sectional associations between DUED and symptom severity, (iv) associations between DUED and clinical outcomes, or (v) experimental manipulation of DUED. Study quality was assessed. RESULTS: Fourteen studies from seven countries were included. Across studies, average DUED weighted by sample size was 29.9 months for anorexia nervosa, 53.0 months for bulimia nervosa and 67.4 months for binge eating disorder. A younger age at time of first treatment was indicative of shorter DUED. Retrospective studies suggest that a shorter DUED may be related to a greater likelihood of remission. Manipulation of DUED by shortening service-related delays may improve clinical outcomes. CONCLUSIONS: Data on length of DUED provide a benchmark for early intervention in EDs. Preliminary evidence suggests DUED may be a modifiable factor influencing outcomes in EDs. To accurately determine the role of DUED, definition and measurement must be uniformly operationalised. Highlights This systematic review is the first to examine duration of untreated eating disorder (DUED) across different eating disorders. Definitions and measurement of DUED and its components vary considerably between studies. Across different eating disorders average DUED weighted by sample size ranges from approximately two and a half years (for anorexia nervosa) to nearly 6 years (for binge eating disorder). DUED appears to be related to age such that younger patients have shorter DUED.

Crowdsourcing image analysis for plant phenomics to generate ground truth data for machine learning.

The accuracy of machine learning tasks critically depends on high quality ground truth data. Therefore, in many cases, producing good ground truth data typically involves trained professionals; however, this can be costly in time, effort, and money. Here we explore the use of crowdsourcing to generate a large number of training data of good quality. We explore an image analysis task involving the segmentation of corn tassels from images taken in a field setting. We investigate the accuracy, speed and other quality metrics when this task is performed by students for academic credit, Amazon MTurk workers, and Master Amazon MTurk workers. We conclude that the Amazon MTurk and Master Mturk workers perform significantly better than the for-credit students, but with no significant difference between the two MTurk worker types. Furthermore, the quality of the segmentation produced by Amazon MTurk workers rivals that of an expert worker. We provide best practices to assess the quality of ground truth data, and to compare data quality produced by different sources. We conclude that properly managed crowdsourcing can be used to establish large volumes of viable ground truth data at a low cost and high quality, especially in the context of high throughput plant phenotyping. We also provide several metrics for assessing the quality of the generated datasets.

Reference frames in spatial updating when body-based cues are absent.

The current study investigated the reference frame used in spatial updating when idiothetic cues to self-motion were minimized (desktop virtual reality). In Experiment 1, participants learned a layout of eight objects from a single perspective (learning heading) in a virtual environment. After learning, they were placed in the same virtual environment and used a keyboard to navigate to two of the learned objects (visible) before pointing to a third object (invisible). We manipulated participants' starting orientation (initial heading) and final orientation (final heading) before pointing, to examine the reference frame used in this task. We found that participants used the initial heading and the learning heading to establish reference directions. In Experiment 2, the procedure was almost the same as in Experiment 1 except that participants pointed to objects relative to an imagined heading that differed from their final heading in the virtual environment. In this case, pointing performance was only affected by alignment with the learning heading. We concluded that the initial heading played an important role in spatial updating without idiothetic cues, but the representation established at this heading was transient and affected by the interruption of spatial updating; the learning heading, on the other hand, corresponded to an enduring representation which was used consistently.

Optimal combination of environmental cues and path integration during navigation.

Navigation is influenced by body-based self-motion cues that are integrated over time, in a process known as path integration, as well as by environmental cues such as landmarks and room shape. In two experiments we explored whether humans combine path integration and environmental cues (Exp. 1: room shape; Exp. 2: room shape, single landmark, and multiple landmarks) to reduce response variability when returning to a previously visited location. Participants walked an outbound path in an immersive virtual environment before attempting to return to the path origin. Path integration and an environmental cue were both available during the outbound path, but experimental manipulations created single- and dual-cue conditions during the return path. The response variance when returning to the path origin was reduced when both cues were available, consistent with optimal integration predicted on the basis of Bayesian principles. The findings indicate that humans optimally integrate multiple spatial cues during navigation. Additionally, a large (but not a small) cue conflict caused participants to assign a higher weight to path integration than to environmental cues, despite the relatively greater precision afforded by the environmental cues.

Selection of macroreference frames in spatial memory.

Spatial memories are often hierarchically organized with different regions of space represented in unique clusters within the hierarchy. Each cluster is thought to be organized around its own microreference frame selected during learning, whereas relationships between clusters are organized by a macroreference frame. Two experiments were conducted in order to better understand important characteristics of macroreference frames. Participants learned overlapping spatial layouts of objects within a room-sized environment before performing a perspective-taking task from memory. Of critical importance were between-layout judgments thought to reflect the macroreference frame. The results indicate that (1) macroreference frames characterize overlapping spatial layouts, (2) macroreference frames are used even when microreference frames are aligned with one another, and (3) macroreference frame selection depends on an interaction between the global macroaxis (defined by characteristics of the layout of all learned objects), the relational macroaxis (defined by characteristics of the two layouts being related on a perspective-taking trial), and the learning view. These results refine the current understanding of macroreference frames and document their broad role in spatial memory.

Cue combination in human spatial navigation.

This project investigated the ways in which visual cues and bodily cues from self-motion are combined in spatial navigation. Participants completed a homing task in an immersive virtual environment. In Experiments 1A and 1B, the reliability of visual cues and self-motion cues was manipulated independently and within-participants. Results showed that participants weighted visual cues and self-motion cues based on their relative reliability and integrated these two cue types optimally or near-optimally according to Bayesian principles under most conditions. In Experiment 2, the stability of visual cues was manipulated across trials. Results indicated that cue instability affected cue weights indirectly by influencing cue reliability. Experiment 3 was designed to mislead participants about cue reliability by providing distorted feedback on the accuracy of their performance. Participants received feedback that their performance with visual cues was better and that their performance with self-motion cues was worse than it actually was or received the inverse feedback. Positive feedback on the accuracy of performance with a given cue improved the relative precision of performance with that cue. Bayesian principles still held for the most part. Experiment 4 examined the relations among the variability of performance, rated confidence in performance, cue weights, and spatial abilities. Participants took part in the homing task over two days and rated confidence in their performance after every trial. Cue relative confidence and cue relative reliability had unique contributions to observed cue weights. The variability of performance was less stable than rated confidence over time. Participants with higher mental rotation scores performed relatively better with self-motion cues than visual cues. Across all four experiments, consistent correlations were found between observed weights assigned to cues and relative reliability of cues, demonstrating that the cue-weighting process followed Bayesian principles. Results also pointed to the important role of subjective evaluation of performance in the cue-weighting process and led to a new conceptualization of cue reliability in human spatial navigation.

Rapid cell death is preceded by amyloid plaque-mediated oxidative stress.

Neuronal loss is the ultimate outcome in a variety of neurodegenerative diseases and central nerve system disorders. Understanding the sequelae of events that leads to cell death would provide insight into neuroprotective approaches. We imaged neurons in the living brain of a mouse model of Alzheimer's disease that overexpresses mutant human amyloid precursor protein and presenilin 1 and followed the death of individual neurons in real time. This mouse model exhibited limited neurodegeneration and atrophy, but we were able to identify a small fraction of vulnerable cells that would not have been detectable by using standard approaches. By exploiting a genetically encoded reporter of oxidative stress, we identified susceptible neurons by their increased redox potential. The oxidative stress was most dramatic in neurites near plaques, propagated to cell bodies, and preceded activation of caspases that led to cell death within 24 h. Thus, local oxidative stress surrounding plaques contributes to long-range toxicity and selective neuronal death in Alzheimer's disease.

Autism occurrence by MMR vaccine status among US children with older siblings with and without autism.

IMPORTANCE: Despite research showing no link between the measles-mumps-rubella (MMR) vaccine and autism spectrum disorders (ASD), beliefs that the vaccine causes autism persist, leading to lower vaccination levels. Parents who already have a child with ASD may be especially wary of vaccinations. OBJECTIVE: To report ASD occurrence by MMR vaccine status in a large sample of US children who have older siblings with and without ASD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using an administrative claims database associated with a large commercial health plan. Participants included children continuously enrolled in the health plan from birth to at least 5 years of age during 2001-2012 who also had an older sibling continuously enrolled for at least 6 months between 1997 and 2012. EXPOSURES: MMR vaccine receipt (0, 1, 2 doses) between birth and 5 years of age. MAIN OUTCOMES AND MEASURES: ASD status defined as 2 claims with a diagnosis code in any position for autistic disorder or other specified pervasive developmental disorder (PDD) including Asperger syndrome, or unspecified PDD (International Classification of Diseases, Ninth Revision, Clinical Modification 299.0x, 299.8x, 299.9x). RESULTS: Of 95,727 children with older siblings, 994 (1.04%) were diagnosed with ASD and 1929 (2.01%) had an older sibling with ASD. Of those with older siblings with ASD, 134 (6.9%) had ASD, vs 860 (0.9%) children with unaffected siblings (P < .001). MMR vaccination rates (≥1 dose) were 84% (n = 78,564) at age 2 years and 92% (n = 86,063) at age 5 years for children with unaffected older siblings, vs 73% (n = 1409) at age 2 years and 86% (n = 1660) at age 5 years for children with affected siblings. MMR vaccine receipt was not associated with an increased risk of ASD at any age. For children with older siblings with ASD, at age 2, the adjusted relative risk (RR) of ASD for 1 dose of MMR vaccine vs no vaccine was 0.76 (95% CI, 0.49-1.18; P = .22), and at age 5, the RR of ASD for 2 doses compared with no vaccine was 0.56 (95% CI, 0.31-1.01; P = .052). For children whose older siblings did not have ASD, at age 2, the adjusted RR of ASD for 1 dose was 0.91 (95% CI, 0.67-1.20; P = .50) and at age 5, the RR of ASD for 2 doses was 1.12 (95% CI, 0.78-1.59; P = .55). CONCLUSIONS AND RELEVANCE: In this large sample of privately insured children with older siblings, receipt of the MMR vaccine was not associated with increased risk of ASD, regardless of whether older siblings had ASD. These findings indicate no harmful association between MMR vaccine receipt and ASD even among children already at higher risk for ASD.

Collaborative inhibition in spatial memory retrieval.

Collaborative inhibition refers to the finding that pairs of people working together to retrieve information from memory-a collaborative group-often retrieve fewer unique items than do nominal pairs, who retrieve individually but whose performance is pooled. Two experiments were designed to explore whether collaborative inhibition, which has heretofore been studied using traditional memory stimuli such as word lists, also characterizes spatial memory retrieval. In the present study, participants learned a layout of objects and then reconstructed the layout from memory, either individually or in pairs. The layouts created by collaborative pairs were more accurate than those created by individuals, but less accurate than those of nominal pairs, providing evidence for collaborative inhibition in spatial memory retrieval. Collaborative inhibition occurred when participants were allowed to dictate the order of object placement during reconstruction (Exp. 1), and also when object order was imposed by the experimenter (Exp. 2), which was intended to disrupt the retrieval processes of pairs as well as of individuals. Individual tests of perspective taking indicated that the underlying representations of pair members were no different than those of individuals; in all cases, spatial memories were organized around a reference frame aligned with the studied perspective. These results suggest that inhibition is caused by the product of group recall (i.e., seeing a partner's object placement), not by the process of group recall (i.e., taking turns choosing an object to place). The present study has implications for how group performance on a collaborative spatial memory task may be optimized.

Cross-sensory reference frame transfer in spatial memory: the case of proprioceptive learning.

In three experiments, we investigated whether the information available to visual perception prior to encoding the locations of objects in a path through proprioception would influence the reference direction from which the spatial memory was formed. Participants walked a path whose orientation was misaligned to the walls of the enclosing room and to the square sheet that covered the path prior to learning (Exp. 1) and, in addition, to the intrinsic structure of a layout studied visually prior to walking the path and to the orientation of stripes drawn on the floor (Exps. 2 and 3). Despite the availability of prior visual information, participants constructed spatial memories that were aligned with the canonical axes of the path, as opposed to the reference directions primed by visual experience. The results are discussed in the context of previous studies documenting transfer of reference frames within and across perceptual modalities.

Templating gold surfaces with function: a self-assembled dendritic monolayer methodology based on monodisperse polyester scaffolds.

The antibiotic resistance developed among several pathogenic bacterial strains has spurred interest in understanding bacterial adhesion down to a molecular level. Consequently, analytical methods that rely on bioactive and multivalent sensor surfaces are sought to detect and suppress infections. To deliver functional sensor surfaces with an optimized degree of molecular packaging, we explore a library of compact and monodisperse dendritic scaffolds based on the nontoxic 2,2-bis(methylol)propionic acid (bis-MPA). A self-assembled dendritic monolayer (SADM) methodology to gold surfaces capitalizes on the design of aqueous soluble dendritic structures that bear sulfur-containing core functionalities. The nature of sulfur (either disulfide or thiol), the size of the dendritic framework (generation 1-3), the distance between the sulfur and the dendritic wedge (4 or 14 Å), and the type of functional end group (hydroxyl or mannose) were key structural elements that were identified to affect the packaging densities assembled on the surfaces. Both surface plasmon resonance (SPR) and resonance-enhanced surface impedance (RESI) experiments revealed rapid formation of homogenously covered SADMs on gold surfaces. The array of dendritic structures enabled the fabrication of functional gold surfaces displaying molecular covering densities of 0.33-2.2 molecules·nm(-2) and functional availability of 0.95-5.5 groups·nm(-2). The cell scavenging ability of these sensor surfaces for Escherichia coli MS7fim+ bacteria revealed 2.5 times enhanced recognition for G3-mannosylated surfaces when compared to G3-hydroxylated SADM surfaces. This promising methodology delivers functional gold sensor surfaces and represents a facile route for probing surface interactions between multivalently presented motifs and cells in a controlled surface setting.

Integrating spatial information across experiences.

The current study examined the potential influence of existing spatial knowledge on the coding of new spatial information. In the Main experiment, participants learned the locations of five objects before completing a perspective-taking task. Subsequently, they studied the same five objects and five additional objects from a new location before completing a second perspective-taking task. Task performance following the first learning phase was best from perspectives aligned with the learning view. However, following the second learning phase, performance was best from the perspective aligned with the second view. A supplementary manipulation increased the salience of the initial view through environmental structure as well as the number of objects present. Results indicated that the initial learning view was preferred throughout the experiment. The role of assimilation and accommodation mechanisms in spatial memory, and the conditions under which they occur, are discussed.

Distance Perception in Virtual Reality: A Meta-Analysis of the Effect of Head-Mounted Display Characteristics.

Distances are commonly underperceived in virtual reality (VR), and this finding has been documented repeatedly over more than two decades of research. Yet, there is evidence that perceived distance is more accurate in modern compared to older head-mounted displays (HMDs). This meta-analysis, based on 137 samples from 61 publications, describes egocentric distance perception across 20 HMDs and examines the relationship between perceived distance and technical HMD characteristics. Judged distance was positively associated with HMD field of view (FOV), positively associated with HMD resolution, and negatively associated with HMD weight. The effects of FOV and resolution were more pronounced among heavier HMDs. These findings suggest that future improvements in these technical characteristics may be central to resolving the problem of distance underperception in VR.

Individual differences in teleporting through virtual environments.

Virtual reality (VR) allows users to walk to explore the virtual environment (VE), but this capability is constrained by real obstacles. Teleporting interfaces overcome this constraint by allowing users to select a position, and sometimes orientation, in the VE before being instantly transported without self-motion cues. This study investigated whether individual differences in navigation performance when teleporting correspond to characteristics of the individual, including spatial ability. Participants performed triangle completion (traverse two outbound path legs, then point to the path origin) within VEs differing in visual landmarks. Locomotion was accomplished using three interfaces: walking, partially concordant teleporting (teleport to change position, rotate the body to change orientation), and discordant teleporting (teleport to change position and orientation). A latent profile analysis identified three profiles of individuals: those who performed well overall and improved with landmarks, those who performed poorly without landmarks but improved when available, and those who performed poorly even with landmarks. Characteristics of individuals differed across profiles, including gender, self-reported spatial ability, mental rotation, and perspective-taking; but only perspective-taking significantly distinguished all three profiles. This work elucidates spatial cognitive correlates of navigation and provides a framework for identifying susceptibility to disorientation in VR. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Preliminary results from the LUX-Dx insertable cardiac monitor remote programming and performance (LUX-Dx PERFORM) study.

Despite the wide adoption of insertable cardiac monitors (ICMs), high false-positive rates, suboptimal signal quality, limited ability to detect atrial flutter, and lack of remote programming remain challenging. The LUX-Dx PERFORM study was designed to evaluate novel technologies engineered to address these issues. Here, we present preliminary results from the trial focusing on the safety of ICM insertion, remote monitoring rates, and the feasibility of remote programming. LUX-Dx PERFORM is a multicenter, prospective, single-arm, post-market, observational study with planned enrollment of up to 827 patients from 35 sites in North America. A preliminary cohort consisting of the first 369 patients who were enrolled between March and October 2021 was selected for analysis. Three hundred sixty-three (363) patients had ICM insertions across inpatient and outpatient settings. The mean time followed was 103.4 ± 61.8 days per patient. The total infection rate was 0.8% (3/363). Interim results show high levels of remote monitoring with a median 94% of days with data transmission (interquartile range: 82-99). Thirteen (13) in-clinic and 24 remote programming sessions were reported in 34 subjects. Reprogramming examples are presented to highlight signal quality, the ability to detect atrial flutter, and the positive impact of remote programming on patient management. Interim results from LUX-Dx PERFORM study demonstrate the safety of insertion, high data transmission rates, the ability to detect atrial flutter, and the feasibility of remote programming to optimize arrhythmia detection and improve clinical workflow. Future results from LUX-Dx PERFORM will further characterize improvements in signal quality and arrhythmia detection.

EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.

EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.

Approach to machine learning for extraction of real-world data variables from electronic health records.

Background: As artificial intelligence (AI) continues to advance with breakthroughs in natural language processing (NLP) and machine learning (ML), such as the development of models like OpenAI's ChatGPT, new opportunities are emerging for efficient curation of electronic health records (EHR) into real-world data (RWD) for evidence generation in oncology. Our objective is to describe the research and development of industry methods to promote transparency and explainability. Methods: We applied NLP with ML techniques to train, validate, and test the extraction of information from unstructured documents (e.g., clinician notes, radiology reports, lab reports, etc.) to output a set of structured variables required for RWD analysis. This research used a nationwide electronic health record (EHR)-derived database. Models were selected based on performance. Variables curated with an approach using ML extraction are those where the value is determined solely based on an ML model (i.e. not confirmed by abstraction), which identifies key information from visit notes and documents. These models do not predict future events or infer missing information. Results: We developed an approach using NLP and ML for extraction of clinically meaningful information from unstructured EHR documents and found high performance of output variables compared with variables curated by manually abstracted data. These extraction methods resulted in research-ready variables including initial cancer diagnosis with date, advanced/metastatic diagnosis with date, disease stage, histology, smoking status, surgery status with date, biomarker test results with dates, and oral treatments with dates. Conclusion: NLP and ML enable the extraction of retrospective clinical data in EHR with speed and scalability to help researchers learn from the experience of every person with cancer.

Capsule robot pose and mechanism state detection in ultrasound using attention-based hierarchical deep learning.

Ingestible robotic capsules with locomotion capabilities and on-board sampling mechanism have great potential for non-invasive diagnostic and interventional use in the gastrointestinal tract. Real-time tracking of capsule location and operational state is necessary for clinical application, yet remains a significant challenge. To this end, we propose an approach that can simultaneously determine the mechanism state and in-plane 2D pose of millimeter capsule robots in an anatomically representative environment using ultrasound imaging. Our work proposes an attention-based hierarchical deep learning approach and adapts the success of transfer learning towards solving the multi-task tracking problem with limited dataset. To train the neural networks, we generate a representative dataset of a robotic capsule within ex-vivo porcine stomachs. Experimental results show that the accuracy of capsule state classification is 97%, and the mean estimation errors for orientation and centroid position are 2.0 degrees and 0.24 mm (1.7% of the capsule's body length) on the hold-out test set. Accurate detection of the capsule while manipulated by an external magnet in a porcine stomach and colon is also demonstrated. The results suggest our proposed method has the potential for advancing the wireless capsule-based technologies by providing accurate detection of capsule robots in clinical scenarios.

Remote research on locomotion interfaces for virtual reality: Replication of a lab-based study on teleporting interfaces.

The wide availability of consumer-oriented virtual reality (VR) equipment has enabled researchers to recruit existing VR owners to participate remotely using their own equipment. Yet, there are many differences between lab environments and home environments, as well as differences between participant samples recruited for lab studies and remote studies. This paper replicates a lab-based experiment on VR locomotion interfaces using a remote sample. Participants completed a triangle-completion task (travel two path legs, then point to the path origin) using their own VR equipment in a remote, unsupervised setting. Locomotion was accomplished using two versions of the teleporting interface varying in availability of rotational self-motion cues. The size of the traveled path and the size of the surrounding virtual environment were also manipulated. Results from remote participants largely mirrored lab results, with overall better performance when rotational self-motion cues were available. Some differences also occurred, including a tendency for remote participants to rely less on nearby landmarks, perhaps due to increased competence with using the teleporting interface to update self-location. This replication study provides insight for VR researchers on aspects of lab studies that may or may not replicate remotely.