Publications by authors named "David Pitcher"

103 Publications

Reusable snorkel masks adapted as particulate respirators.

PLoS One 2021 5;16(4):e0249201. Epub 2021 Apr 5.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Introduction: During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject's face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/.

Conclusion: Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249201PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021169PMC
April 2021

Theta-burst TMS of lateral occipital cortex reduces BOLD responses across category-selective areas in ventral temporal cortex.

Neuroimage 2021 04 23;230:117790. Epub 2021 Jan 23.

Section on Learning and Plasticity, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892-1366, United States.

Human visual cortex contains three scene-selective regions in the lateral, medial and ventral cortex, termed the occipital place area (OPA), medial place area (MPA) and parahippocampal place area (PPA). Using functional magnetic resonance imaging (fMRI), all three regions respond more strongly when viewing visual scenes compared with isolated objects or faces. To determine how these regions are functionally and causally connected, we applied transcranial magnetic stimulation to OPA and measured fMRI responses before and after stimulation, using a theta-burst paradigm (TBS). To test for stimulus category-selectivity, we presented a range of visual categories (scenes, buildings, objects, faces). To test for specificity of any effects to TBS of OPA we employed two control conditions: Sham, with no TBS stimulation, and an active TBS-control with TBS to a proximal face-selective cortical region (occipital face area, or OFA). We predicted that TBS to OPA (but not OFA) would lead to decreased responses to scenes and buildings (but not other categories) in other scene-selective cortical regions. Across both ROI and whole-volume analyses, we observed decreased responses to scenes in PPA as a result of TBS. However, these effects were neither category specific, with decreased responses to all stimulus categories, nor limited to scene-selective regions, with decreases also observed in face-selective fusiform face area (FFA). Furthermore, similar effects were observed with TBS to OFA, thus effects were not specific to the stimulation site in the lateral occipital cortex. Whilst these data are suggestive of a causal, but non-specific relationship between lateral occipital and ventral temporal cortex, we discuss several factors that could have underpinned this result, such as the differences between TBS and online TMS, the role of anatomical distance between stimulated regions and how TMS effects are operationalised. Furthermore, our findings highlight the importance of active control conditions in brain stimulation experiments to accurately assess functional and causal connectivity between specific brain regions.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117790DOI Listing
April 2021

Evidence for a Third Visual Pathway Specialized for Social Perception.

Trends Cogn Sci 2021 02 14;25(2):100-110. Epub 2020 Dec 14.

Section on Neurocircuitry, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892, USA.

Existing models propose that primate visual cortex is divided into two functionally distinct pathways. The ventral pathway computes the identity of an object; the dorsal pathway computes the location of an object, and the actions related to that object. Despite remaining influential, the two visual pathways model requires revision. Both human and non-human primate studies reveal the existence of a third visual pathway on the lateral brain surface. This third pathway projects from early visual cortex, via motion-selective areas, into the superior temporal sulcus (STS). Studies demonstrating that the STS computes the actions of moving faces and bodies (e.g., expressions, eye-gaze, audio-visual integration, intention, and mood) show that the third visual pathway is specialized for the dynamic aspects of social perception.
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http://dx.doi.org/10.1016/j.tics.2020.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811363PMC
February 2021

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis.

PLoS One 2020 23;15(10):e0241263. Epub 2020 Oct 23.

UK Renal Registry, The Renal Association, Bristol, United Kingdom.

Kidney disease is a recognised risk factor for poor COVID-19 outcomes. Up to 30 June 2020, the UK Renal Registry (UKRR) collected data for 2,385 in-centre haemodialysis (ICHD) patients with COVID-19 in England and Wales. Overall unadjusted survival at 1 week after date of positive COVID-19 test was 87.5% (95% CI 86.1-88.8%); mortality increased with age, treatment vintage and there was borderline evidence of Asian ethnicity (HR 1.16, 95% CI 0.94-1.44) being associated with higher mortality. Compared to the general population, the relative risk of mortality for ICHD patients with COVID-19 was 45.4 and highest in younger adults. This retrospective cohort study based on UKRR data supports efforts to protect this vulnerable patient group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241263PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584244PMC
November 2020

Transcranial Magnetic Stimulation and the Understanding of Behavior.

Annu Rev Psychol 2021 01 23;72:97-121. Epub 2020 Oct 23.

Institute of Cognitive Neuroscience, University College London, London WC1N 3AR, United Kingdom; email:

The development of the use of transcranial magnetic stimulation (TMS) in the study of psychological functions has entered a new phase of sophistication. This is largely due to an increasing physiological knowledge of its effects and to its being used in combination with other experimental techniques. This review presents the current state of our understanding of the mechanisms of TMS in the context of designing and interpreting psychological experiments. We discuss the major conceptual advances in behavioral studies using TMS. There are meaningful physiological and technical achievements to review, as well as a wealth of new perceptual and cognitive experiments. In doing so we summarize the different uses and challenges of TMS in mental chronometry, perception, awareness, learning, and memory.
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http://dx.doi.org/10.1146/annurev-psych-081120-013144DOI Listing
January 2021

Prolonged ursodeoxycholic acid administration reduces acute ischaemia-induced arrhythmias in adult rat hearts.

Sci Rep 2020 09 17;10(1):15284. Epub 2020 Sep 17.

National Heart and Lung Institute, Imperial College London, London, UK.

Acute myocardial ischaemia and reperfusion (I-R) are major causes of ventricular arrhythmias in patients with a history of coronary artery disease. Ursodeoxycholic acid (UDCA) has previously been shown to be antiarrhythmic in fetal hearts. This study was performed to investigate if UDCA protects against ischaemia-induced and reperfusion-induced arrhythmias in the adult myocardium, and compares the effect of acute (perfusion only) versus prolonged (2 weeks pre-treatment plus perfusion) UDCA administration. Langendorff-perfused adult Sprague-Dawley rat hearts were subjected to acute regional ischaemia by ligation of the left anterior descending artery (10 min), followed by reperfusion (2 min), and arrhythmia incidence quantified. Prolonged UDCA administration reduced the incidence of acute ischaemia-induced arrhythmias (p = 0.028), with a reduction in number of ventricular ectopic beats during the ischaemic phase compared with acute treatment (10 ± 3 vs 58 ± 15, p = 0.036). No antiarrhythmic effect was observed in the acute UDCA administration group. Neither acute nor prolonged UDCA treatment altered the incidence of reperfusion arrhythmias. The antiarrhythmic effect of UDCA may be partially mediated by an increase in cardiac wavelength, due to the attenuation of conduction velocity slowing (p = 0.03), and the preservation of Connexin43 phosphorylation during acute ischaemia (p = 0.0027). The potential antiarrhythmic effects of prolonged UDCA administration merit further investigation.
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http://dx.doi.org/10.1038/s41598-020-72016-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499428PMC
September 2020

Theta-burst TMS to the posterior superior temporal sulcus decreases resting-state fMRI connectivity across the face processing network.

Netw Neurosci 2020 1;4(3):746-760. Epub 2020 Aug 1.

Department of Psychology, University of York, Heslington, York, UK.

Humans process faces by using a network of face-selective regions distributed across the brain. Neuropsychological patient studies demonstrate that focal damage to nodes in this network can impair face recognition, but such patients are rare. We approximated the effects of damage to the face network in neurologically normal human participants by using theta burst transcranial magnetic stimulation (TBS). Multi-echo functional magnetic resonance imaging (fMRI) resting-state data were collected pre- and post-TBS delivery over the face-selective right superior temporal sulcus (rpSTS), or a control site in the right motor cortex. Results showed that TBS delivered over the rpSTS reduced resting-state connectivity across the extended face processing network. This connectivity reduction was observed not only between the rpSTS and other face-selective areas, but also between nonstimulated face-selective areas across the ventral, medial, and lateral brain surfaces (e.g., between the right amygdala and bilateral fusiform face areas and occipital face areas). TBS delivered over the motor cortex did not produce significant changes in resting-state connectivity across the face processing network. These results demonstrate that, even without task-induced fMRI signal changes, disrupting a single node in a brain network can decrease the functional connectivity between nodes in that network that have not been directly stimulated.
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http://dx.doi.org/10.1162/netn_a_00145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462428PMC
August 2020

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling.

Pflugers Arch 2020 10 1;472(10):1435-1446. Epub 2020 Sep 1.

Faculty of Medicine, National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.

We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far-field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting. Porcine (n = 9) and human (n = 4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. A total of 1 mM of carbenoxolone was administered at 5 ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed. We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt) increased between baseline and carbenoxolone (47.9 ± 4.1-67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and carbenoxolone were fractionation + 185.3%, endpoint amplitude - 106.9%, S-endpoint gradient + 54.9%, S point - 39.4%, RS ratio + 38.6% and (-dV/dt) - 20.9%. The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically induced pro-arrhythmic substrates.
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http://dx.doi.org/10.1007/s00424-020-02446-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476990PMC
October 2020

Dissociable pathways for moving and static face perception begin in early visual cortex: Evidence from an acquired prosopagnosic.

Cortex 2020 09 3;130:327-339. Epub 2020 Jul 3.

Department of Psychology, University of York, Heslington, York, UK. Electronic address:

To investigate the functional connections between the core components of the face processing network we tested Herschel, an acquired prosopagnosic patient with a right ventral occipitotemporal lesion. In Experiment 1, Herschel, and control participants, were scanned with functional magnetic resonance imaging (fMRI) while viewing videos of moving faces, or static images taken from the videos. In Experiment 2, participants viewed videos of actors making facial expressions, or static images taken from the videos. In Experiment 3, participants viewed videos of moving faces presented in the left or right visual field. Results showed the neural response in Herschel's right occipital face area (OFA) was impaired for moving and static faces (Experiment 1), moving expressions (Experiment 2) and moving faces in the left visual field (Experiment 3). The response in Herschel's right fusiform face area (FFA) to moving and static faces was impaired in Experiment 1 only, in Experiments 2 and 3 Herschel's FFA response was not significantly different from controls. By contrast, the response in Herschel's right posterior superior temporal sulcus (rpSTS) to moving and static faces and expressions (Experiments 1 and 2) and the visual field response (Experiment 3) was not significantly different from control participants. Our results demonstrate there are cortico-cortical inputs to the pSTS from early visual cortex that are independent of the OFA, a conclusion inconsistent with established models of face processing.
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http://dx.doi.org/10.1016/j.cortex.2020.03.033DOI Listing
September 2020

Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern.

Cardiovasc Res 2021 Mar;117(4):1078-1090

National Heart & Lung Institute, Imperial College London, 4th Floor, ICTEM Building, 72 Du Cane Road, London W12 0NN, UK.

Aims: Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.

Methods And Results: Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P < 0.001), increasing RA-sustained VF time (0 nM: 44 ± 6%, 80 nM: 94 ± 2%, P < 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM: 5.4 ± 0.5, 80 nM: 48.2 ± 12.3, P < 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM: 0.60 ± 0.05, 50 µM: 0.17 ± 0.03, P < 0.001) and RA-sustained VF time decreased (0 µM: 61 ± 9%, 50 µM: 3 ± 2%, P < 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF: 27 ± 7% vs. PF: 75 ± 5%, P < 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF: 0.67 ± 0.05 vs. CF: 0.33 ± 0.03, P < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411 ± 266 ms vs. compact: 354 ± 38 ms, P < 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.

Conclusion: The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.
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http://dx.doi.org/10.1093/cvr/cvaa141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983010PMC
March 2021

Dual-site TMS demonstrates causal functional connectivity between the left and right posterior temporal sulci during facial expression recognition.

Brain Stimul 2020 Jul - Aug;13(4):1008-1013. Epub 2020 Apr 23.

Department of Psychology, University of York, Heslington, York, YO10 5DD, UK.

Background: Neuroimaging studies suggest that facial expression recognition is processed in the bilateral posterior superior temporal sulcus (pSTS). Our recent repetitive transcranial magnetic stimulation (rTMS) study demonstrates that the bilateral pSTS is causally involved in expression recognition, although involvement of the right pSTS is greater than involvement of the left pSTS.

Objective: /Hypothesis: In this study, we used a dual-site TMS to investigate whether the left pSTS is functionally connected to the right pSTS during expression recognition. We predicted that if this connection exists, simultaneous TMS disruption of the bilateral pSTS would impair expression recognition to a greater extent than unilateral stimulation of the right pSTS alone.

Methods: Participants attended two TMS sessions. In Session 1, participants performed an expression recognition task while rTMS was delivered to the face-sensitive right pSTS (experimental site), object-sensitive right lateral occipital complex (control site) or no rTMS was delivered (behavioural control). In Session 2, the same experimental design was used, except that continuous theta-burst stimulation (cTBS) was delivered to the left pSTS immediately before behavioural testing commenced. Session order was counter-balanced across participants.

Results: In Session 1, rTMS to the rpSTS impaired performance accuracy compared to the control conditions. Crucially in Session 2, the size of this impairment effect doubled after cTBS was delivered to the left pSTS.

Conclusions: Our results provide evidence for a causal functional connection between the left and right pSTS during expression recognition. In addition, this study further demonstrates the utility of the dual-site TMS for investigating causal functional links between brain regions.
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http://dx.doi.org/10.1016/j.brs.2020.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301156PMC
December 2020

Development of the Recommended Summary Plan for eEmergency Care and Treatment (ReSPECT).

Resuscitation 2020 03 13;148:98-107. Epub 2020 Jan 13.

Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, UK; University Hospitals Birmingham, NHS Foundation Trust, Birmingham, UK. Electronic address:

Introduction: Do-not-attempt-cardiopulmonary-resuscitation (DNACPR) practice has been shown to be variable and sub-optimal. This paper describes the development of the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT). ReSPECT is a process which encourages shared understanding of a patient's condition and what outcomes they value and fear, before recording clinical recommendations about cardiopulmonary-resuscitation (CPR) within a broader plan for emergency care and treatment.

Methods: ReSPECT was developed iteratively, with integral stakeholder engagement, informed by the Knowledge-to-Action cycle. Mixed methods included: synthesis of existing literature; a national online consultation exercise; cognitive interviews with users; a patient-public involvement (PPI) workshop and a usability pilot, to ensure acceptability by both patients and professionals.

Results: The majority (89%) of consultation respondents supported the concept of emergency care and treatment plans. Key features identified in the evaluation and incorporated into ReSPECT were: The importance of discussions between patient and clinician to inform realistic treatment preferences and clarity in the resulting recommendations recorded by the clinician on the form. The process is compliant with UK mental capacity laws. Documentation should be recognised across all health and care settings. There should be opportunity for timely review based on individual need.

Conclusion: ReSPECT is designed to facilitate discussions about a person's preferences to inform emergency care and treatment plans (including CPR) for use across all health and care settings. It has been developed iteratively with a range of stakeholders. Further research will be needed to assess the influence of ReSPECT on patient-centred decisions, experience and health outcomes.
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http://dx.doi.org/10.1016/j.resuscitation.2020.01.003DOI Listing
March 2020

The Human Posterior Superior Temporal Sulcus Samples Visual Space Differently From Other Face-Selective Regions.

Cereb Cortex 2020 03;30(2):778-785

Section on Neurocircuitry, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD 20892, USA.

Neuroimaging studies show that ventral face-selective regions, including the fusiform face area (FFA) and occipital face area (OFA), preferentially respond to faces presented in the contralateral visual field (VF). In the current study we measured the VF response of the face-selective posterior superior temporal sulcus (pSTS). Across 3 functional magnetic resonance imaging experiments, participants viewed face videos presented in different parts of the VF. Consistent with prior results, we observed a contralateral VF bias in bilateral FFA, right OFA (rOFA), and bilateral human motion-selective area MT+. Intriguingly, this contralateral VF bias was absent in the bilateral pSTS. We then delivered transcranial magnetic stimulation (TMS) over right pSTS (rpSTS) and rOFA, while participants matched facial expressions in both hemifields. TMS delivered over the rpSTS disrupted performance in both hemifields, but TMS delivered over the rOFA disrupted performance in the contralateral hemifield only. These converging results demonstrate that the contralateral bias for faces observed in ventral face-selective areas is absent in the pSTS. This difference in VF response is consistent with face processing models proposing 2 functionally distinct pathways. It further suggests that these models should account for differences in interhemispheric connections between the face-selective areas across these 2 pathways.
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http://dx.doi.org/10.1093/cercor/bhz125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306171PMC
March 2020

A functional dissociation of face-, body- and scene-selective brain areas based on their response to moving and static stimuli.

Sci Rep 2019 06 3;9(1):8242. Epub 2019 Jun 3.

Section on Neurocircuitry, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD, 20892, USA.

The human brain contains areas that respond selectively to faces, bodies and scenes. Neuroimaging studies have shown that a subset of these areas preferentially respond more to moving than static stimuli, but the reasons for this functional dissociation remain unclear. In the present study, we simultaneously mapped the responses to motion in face-, body- and scene-selective areas in the right hemisphere using moving and static stimuli. Participants (N = 22) were scanned using functional magnetic resonance imaging (fMRI) while viewing videos containing bodies, faces, objects, scenes or scrambled objects, and static pictures from the beginning, middle and end of each video. Results demonstrated that lateral areas, including face-selective areas in the posterior and anterior superior temporal sulcus (STS), the extrastriate body area (EBA) and the occipital place area (OPA) responded more to moving than static stimuli. By contrast, there was no difference between the response to moving and static stimuli in ventral and medial category-selective areas, including the fusiform face area (FFA), occipital face area (OFA), amygdala, fusiform body area (FBA), retrosplenial complex (RSC) and parahippocampal place area (PPA). This functional dissociation between lateral and ventral/medial brain areas that respond selectively to different visual categories suggests that face-, body- and scene-selective networks may be functionally organized along a common dimension.
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http://dx.doi.org/10.1038/s41598-019-44663-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546694PMC
June 2019

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.

Cancer Cell 2018 10;34(4):596-610.e11

Centre for Haematology, Department of Medicine, Imperial College London, London, UK. Electronic address:

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19 B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo. The swifter in vivo anti-lymphoma activity of CAR19-iNKT cells and their enhanced ability to eradicate brain lymphomas underpinned an improved tumor-free and overall survival. CD1D transcriptional de-repression by all-trans retinoic acid results in further enhanced cytotoxicity of CAR19-iNKT cells against CD19 chronic lymphocytic leukemia cells. Thus, iNKT cells are a highly efficient platform for CAR-based immunotherapy of lymphomas and possibly other CD1d-expressing cancers.
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http://dx.doi.org/10.1016/j.ccell.2018.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179961PMC
October 2018

TMS demonstrates that both right and left superior temporal sulci are important for facial expression recognition.

Neuroimage 2018 12 18;183:394-400. Epub 2018 Aug 18.

Department of Psychology, University of York, Heslington, York, YO10 5DD, UK.

Prior studies demonstrate that a face-responsive region in the posterior superior temporal sulcus (pSTS) is involved in facial expression recognition. Although this region can be identified in both hemispheres, studies more commonly report it in the right hemisphere. However, the extent to which expression recognition is lateralised in pSTS remains unclear. In the current study, we used transcranial magnetic stimulation (TMS) to systematically compare the causal contribution of the right pSTS (rpSTS) with the left pSTS (lpSTS) during facial expression recognition. TMS was delivered over the functionally localised rpSTS, lpSTS and the control vertex site while participants (N = 30) performed an expression matching task and a control object matching task. TMS delivered over the rpSTS impaired expression recognition more than TMS delivered over the lpSTS. Crucially, TMS delivered over the rpSTS and lpSTS impaired task performance more than TMS delivered over the control site. TMS had no effect on the control task. This causally demonstrates that while task disruption was greater in the rpSTS, both the rpSTS and the lpSTS were engaged in facial expression recognition. Our results indicate that cognitive functions that are seemingly lateralised in neuroimaging studies, still rely on computations performed in both hemispheres for optimum task performance.
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http://dx.doi.org/10.1016/j.neuroimage.2018.08.025DOI Listing
December 2018

Analytical approaches for myocardial fibrillation signals.

Comput Biol Med 2018 11 17;102:315-326. Epub 2018 Jul 17.

ElectroCardioMaths, Imperial Centre for Cardiac Engineering, National Heart & Lung Institute, Imperial College London, United Kingdom. Electronic address:

Atrial and ventricular fibrillation are complex arrhythmias, and their underlying mechanisms remain widely debated and incompletely understood. This is partly because the electrical signals recorded during myocardial fibrillation are themselves complex and difficult to interpret with simple analytical tools. There are currently a number of analytical approaches to handle fibrillation data. Some of these techniques focus on mapping putative drivers of myocardial fibrillation, such as dominant frequency, organizational index, Shannon entropy and phase mapping. Other techniques focus on mapping the underlying myocardial substrate sustaining fibrillation, such as voltage mapping and complex fractionated electrogram mapping. In this review, we discuss these techniques, their application and their limitations, with reference to our experimental and clinical data. We also describe novel tools including a new algorithm to map microreentrant circuits sustaining fibrillation.
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http://dx.doi.org/10.1016/j.compbiomed.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215772PMC
November 2018

Characterisation of re-entrant circuit (or rotational activity) in vitro using the HL1-6 myocyte cell line.

J Mol Cell Cardiol 2018 06 7;119:155-164. Epub 2018 May 7.

Myocardial Function, National Heart and Lung Institute, Imperial College London, London, UK. Electronic address:

Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia. Two main concepts are still debated, the "leading circle" and the "spiral wave or rotor" theories. The homogeneous subclone of the HL1 atrial-derived cardiomyocyte cell line, HL1-6, spontaneously exhibits re-entry on a microscopic scale due to its slow conduction velocity and the presence of triggers, making it possible to examine re-entry at the cellular level. We therefore investigated the re-entry cores in cell monolayers through the use of fluorescence optical mapping at high spatiotemporal resolution in order to obtain insights into the mechanisms of re-entry. Re-entries in HL1-6 myocytes required at least two triggers and a minimum colony area to initiate (3.5 to 6.4 mm). After electrical activity was completely stopped and re-started by varying the extracellular K concentration, re-entries never returned to the same location while 35% of triggers re-appeared at the same position. A conduction delay algorithm also allows visualisation of the core of the re-entries. This work has revealed that the core of re-entries is conduction blocks constituted by lines and/or groups of cells rather than the round area assumed by the other concepts of functional re-entry. This highlights the importance of experimentation at the microscopic level in the study of re-entry mechanisms.
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http://dx.doi.org/10.1016/j.yjmcc.2018.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004038PMC
June 2018

How accessible are public-access defibrillators? An observational study at mainline train stations.

Authors:
David Pitcher

Resuscitation 2018 02 1;123:e3-e4. Epub 2017 Dec 1.

Resuscitation Council (UK), Tavistock House North, London, WC1H 9HR, UK. Electronic address:

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http://dx.doi.org/10.1016/j.resuscitation.2017.11.066DOI Listing
February 2018

Algorithms to guide ambulance clinicians in the management of emergencies in patients with implanted rotary left ventricular assist devices.

Emerg Med J 2017 Dec 10;34(12):842-850. Epub 2017 Nov 10.

Resuscitation Council, London, UK.

Advances in left ventricular assist device (LVAD) therapy have resulted in increasing numbers of adult LVAD recipients in the community. However, device failure, stroke, bleeding, LVAD thrombosis and systemic infection can be life-threatening emergencies. Currently, four LVAD systems are implanted in six UK transplant centres, each of which provides device-specific information to local emergency services. This has resulted in inconsistent availability and content of information with the risks of delayed or inappropriate decision-making. In order to improve patient safety, a consortium of UK healthcare professionals with expertise in LVADs developed universally applicable prehospital emergency algorithms. Guidance was framed as closely as possible on the standard ABCDE approach to the assessment of critically ill patients.
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http://dx.doi.org/10.1136/emermed-2016-206172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750371PMC
December 2017

ReSPECT is a personal emergency care plan summary.

BMJ 2017 05 9;357:j2213. Epub 2017 May 9.

ReSPECT expert working group, Resuscitation Council (UK), 5th Floor, Tavistock House North, London WC1H 9HR, UK.

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http://dx.doi.org/10.1136/bmj.j2213DOI Listing
May 2017

Emergency care and resuscitation plans.

BMJ 2017 02 28;356:j876. Epub 2017 Feb 28.

Marie Curie Hospice Edinburgh, UK.

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http://dx.doi.org/10.1136/bmj.j876DOI Listing
February 2017

The Superior Temporal Sulcus Is Causally Connected to the Amygdala: A Combined TBS-fMRI Study.

J Neurosci 2017 02 23;37(5):1156-1161. Epub 2016 Dec 23.

Section on Neurocircuitry, Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, Maryland 20892.

Nonhuman primate neuroanatomical studies have identified a cortical pathway from the superior temporal sulcus (STS) projecting into dorsal subregions of the amygdala, but whether this same pathway exists in humans is unknown. Here, we addressed this question by combining theta burst transcranial magnetic stimulation (TBS) with fMRI to test the prediction that the STS and amygdala are functionally connected during face perception. Human participants (N = 17) were scanned, over two sessions, while viewing 3 s video clips of moving faces, bodies, and objects. During these sessions, TBS was delivered over the face-selective right posterior STS (rpSTS) or over the vertex control site. A region-of-interest analysis revealed results consistent with our hypothesis. Namely, TBS delivered over the rpSTS reduced the neural response to faces (but not to bodies or objects) in the rpSTS, right anterior STS (raSTS), and right amygdala, compared with TBS delivered over the vertex. By contrast, TBS delivered over the rpSTS did not significantly reduce the neural response to faces in the right fusiform face area or right occipital face area. This pattern of results is consistent with the existence of a cortico-amygdala pathway in humans for processing face information projecting from the rpSTS, via the raSTS, into the amygdala. This conclusion is consistent with nonhuman primate neuroanatomy and with existing face perception models.

Significance Statement: Neuroimaging studies have identified multiple face-selective regions in the brain, but the functional connections between these regions are unknown. In the present study, participants were scanned with fMRI while viewing movie clips of faces, bodies, and objects before and after transient disruption of the face-selective right posterior superior temporal sulcus (rpSTS). Results showed that TBS disruption reduced the neural response to faces, but not to bodies or objects, in the rpSTS, right anterior STS (raSTS), and right amygdala. These results are consistent with the existence of a cortico-amygdala pathway in humans for processing face information projecting from the rpSTS, via the raSTS, into the amygdala. This conclusion is consistent with nonhuman primate neuroanatomy and with existing face perception models.
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http://dx.doi.org/10.1523/JNEUROSCI.0114-16.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296794PMC
February 2017

Primary Intraosseous Malignant Peripheral Nerve Sheath Tumor of the Medial Cuneiform: A Case Report and Review of the Literature.

J Foot Ankle Surg 2017 Jan - Feb;56(1):129-134. Epub 2016 Jul 19.

Senior Vice President, Translational Research and Economic Development, Nova Southeastern University, Fort Lauderdale, FL.

Peripheral nerve sheath tumors (benign and malignant) usually arise in the soft tissues and are unusual in bone. Intraosseous peripheral nerve sheath tumors are usually benign and constitute approximately 0.2% of all bone tumors. Intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are uncommon and usually result from secondary invasion. Only a few cases of primary intraosseous MPNSTs have been reported in published studies, and these were localized mostly in the mandible (approximately 50%) or maxilla, spine, and, occasionally, in the appendicular skeleton. To the best of our knowledge, we report the first case of primary intraosseous MPNST involving a midtarsal bone (medial cuneiform). The patient was a 62-year-old female who presented with pain and tenderness but without swelling. Imaging revealed nonspecific findings, and the preoperative computed tomography-guided biopsy findings were consistent with MPNST. The patient was treated with neoadjuvant radiotherapy, followed by wide local excision and allograft reconstruction. At the final follow-up examination (24 months), the graft had been incorporated without evidence of local recurrence or distant disease. The patient with primary intraosseous MPNST of the medial cuneiform described in the present report presented with nonspecific clinical and radiologic findings. Thus, a high index of suspicion and histopathologic examination, including immunohistochemistry, are necessary for an accurate diagnosis.
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http://dx.doi.org/10.1053/j.jfas.2016.05.013DOI Listing
August 2017

Cardiovascular implanted electronic devices in people towards the end of life, during cardiopulmonary resuscitation and after death: guidance from the Resuscitation Council (UK), British Cardiovascular Society and National Council for Palliative Care.

Heart 2016 06;102 Suppl 7:A1-A17

Executive Director, Resuscitation Council (UK), London, UK.

The Resuscitation Council (UK), the British Cardiovascular Society (including the British Heart Rhythm Society and the British Society for Heart Failure) and the National Council for Palliative Care recognise the importance of providing clear and consistent guidance on management of cardiovascular implanted electronic devices (CIEDs) towards the end of life, during cardiorespiratory arrest and after death. This document has been developed to provide guidance for the full range of healthcare professionals who may encounter people with CIEDs in the situations described and for healthcare managers and commissioners. The authors recognise that some patients and people close to patients may also wish to refer to this document. It is intended as an initial step to help to ensure that people who have CIEDs, or are considering implantation of one, receive explanation of and understand the practical implications and decisions that this entails; to promote a good standard of care and service provision for people in the UK with CIEDs in the circumstances described; to offer relevant ethical and legal guidance on this topic; to offer guidance on the delivery of services in relation to deactivation of CIEDs where appropriate; to offer guidance on whether any special measures are needed when a person with a CIED receives cardiopulmonary resuscitation; and to offer guidance on the actions needed when a person with a CIED dies.
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http://dx.doi.org/10.1136/heartjnl-2016-309721DOI Listing
June 2016

Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome Structure.

EBioMedicine 2015 Jul 28;2(7):642-8. Epub 2015 May 28.

Centre for Haematology, Division of Experimental Medicine, Faculty of Medicine, Imperial College London, Hammersmith Campus, Commonwealth Building 4th Floor, Du Cane Road, London W12 0NN, United Kingdom.

The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM). Bortezomib inhibits protein degradation by inactivating proteasomes' active-sites. MM cells are exquisitely sensitive to Bortezomib - exhibiting a low-nanomolar IC(50) - suggesting that minimal inhibition of degradation suffices to kill MM cells. Instead, we report, a low Bortezomib concentration, contrary to expectation, achieves severe inhibition of proteasome activity in MM cells: the degree of inhibition exceeds what one would expect from the small proportion of active-sites that Bortezomib inhibits. Our data indicate that Bortezomib achieves this severe inhibition by triggering secondary changes in proteasome structure that further inhibit proteasome activity. Comparing MM cells to other, Bortezomib-resistant, cancer cells shows that the degree of proteasome inhibition is the greatest in MM cells and only there leads to proteasome stress, providing an explanation for why Bortezomib is effective against MM but not other cancers.
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http://dx.doi.org/10.1016/j.ebiom.2015.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534688PMC
July 2015

Education for cardiac arrest - Prevention AND treatment.

Resuscitation 2015 Nov 20;96:e7. Epub 2015 Jun 20.

Resuscitation Council (UK), United Kingdom.

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http://dx.doi.org/10.1016/j.resuscitation.2015.06.011DOI Listing
November 2015

Intraarticular osteochondroma of the knee.

Indian J Orthop 2015 Mar-Apr;49(2):260-1

Department of Orthopaedics, Miami V.A. Medical Center, Miami, FL, USA.

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http://dx.doi.org/10.4103/0019-5413.152547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436497PMC
May 2015

UK Renal Registry 17th Annual Report: Chapter 12 Epidemiology of Reported Infections amongst Patients Receiving Dialysis for Established Renal Failure in England in 2012 to 2013: a Joint Report from Public Health England and the UK Renal Registry.

Nephron 2015 22;129 Suppl 1:257-65. Epub 2015 Jan 22.

UK Renal Registry, Bristol, UK.

Introduction: Infection remains one of the leading causes of mortality in established renal failure patients receiving renal replacement therapy (RRT).

Methods: Data were submitted to Public Health England (PHE) by NHS acute Trusts via Health Care Associated Infection Data Capture System (HCAI-DCS) including whether the patients were receiving dialysis. Individual renal units then confirmed the record either directly via the database or after being contacted. Data were collected for the period 1st May 2012 to the 30th April 2013.

Results: There were 31 episodes of MRSA bacteraemia, an overall rate of 0.13 per 100 dialysis patient years, representing a further year-on-year fall in MRSA rate. There were a higher number of MSSA episodes, 372 in total,with an overall rate of 1.59 per 100 dialysis patient years. The number of episodes of E. coli and C. difficile were 308 (1.32 per 100 dialysis patient years) and 123 (0.55 per 100 dialysis patient years) respectively. The presence of a central venous catheter was associated with an elevated risk of MRSA and MSSA bacteraemia.

Conclusions: We present data relating to infections in renal dialysis patients reported to PHE in one year. The rate of MRSA bacteraemia episodes in England continues to fall. There is a higher rate of MSSA infections.We also report the results of the second year of E. coli and C. difficile data collection. Future cycles will give further ideas of the trend in incidences of these infections. Further work to refine the definitions and data collection is necessary to ensure consistency of reporting across centres.
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http://dx.doi.org/10.1159/000370282DOI Listing
January 2016

UK Renal Registry 17th Annual Report: Chapter 10 2013 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2012 PD One Year Follow-up: National and Centre-specific Analyses.

Nephron 2015 22;129 Suppl 1:223-45. Epub 2015 Jan 22.

UK Renal Registry, Bristol, UK.

Background: Dialysis access should be timely, minimize complications and maintain functionality. The aim of the second combined vascular and peritoneal dialysis access audit was to examine practice patterns with respect to dialysis access and highlight variations in practice between renal centres.

Methods: The UK Renal Registry collected centre-specific information on incident vascular and peritoneal dialysis access outcome measures in patients from England, Wales and Northern Ireland (EW&NI), including patient demographics, dialysis access type (at start of dialysis and three months after start of dialysis), surgical assessment and access functionality. Centres who had reported data on incident PD patients for the previous 2012 audit were additionally asked to provide one year follow up data for this group. The findings were compared to the audit measures stated in Renal Association clinical practice guidelines for dialysis access.

Results: Fifty-seven centres in EW&NI (representing 92% of all centres) returned data on first access from 3,663 incident HD patients and 1,022 incident PD patients. A strong relationship was seen between surgical assessment and the likelihood of starting HD with an arteriovenous fistula (AVF). Twenty-four centres were at least two standard deviations below the 65% target for incident patients starting haemodialysis on AVF and only eight centres (14%) were within two standard deviations of the 85% target for prevalent haemodialysis patients on AVF.

Conclusions: There was wide practice variation across the UK in provision of both HD and PD access which requires further exploration.
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http://dx.doi.org/10.1159/000370280DOI Listing
January 2016