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Uncovering the neural correlates of the urge-to-blink: A study utilising subjective urge ratings and paradigm free mapping
Get PDFNeuroimaging plays a significant role in understanding the neurophysiology of Tourette syndrome (TS), in particular the main symptom, tics, and the urges associated with them. Premonitory urge is thought to be a negative reinforcer of tic expression in TS. Tic expression during neuroimaging is most often required as an overt marker of increased urge-to-tic, which can lead to considerable head movement, and thus data loss. This study aims to identify the brain regions involved in urge in healthy subjects using multi-echo functional magnetic resonance imaging (fMRI) and a timing-free approach to localise the blood-oxygen level-dependent (BOLD) response associated with the urge-to-act without information of when these events occur. Blink suppression is an analogous behaviour that can be expressed overtly in the MRI scanner which gives rise to an urge like those described by individuals with TS. We examined the urge-to-blink in 20 healthy volunteers with an experimental paradigm including two conditions, “Okay to blink” and “Suppress blinking”, to identify brain regions involved in blink suppression. Multi-echo fMRI data were analysed using a novel approach to investigate the BOLD signal correlated with the build-up of the urge-to-blink that participants continuously reported using a rollerball device. In addition, we used the method of multi-echo paradigm free mapping (MESPFM) to identify these regions without prior specification of task timings. Subjective urge scores were correlated with activity in the right posterior and ventral-anterior insula as well as the mid-cingulate and occipital cortices. Whereas blink suppression was associated with activation in the dorsolateral prefrontal cortex, cerebellum, right dorsal-anterior insula, mid-cingulate cortex, and thalamus. These findings illustrate that different insula subregions contribute to the urge-for-action and suppression networks. The MESPFM approach showed co-activation of the right insula and cingulate cortex. The MESPFM activation maps showed the highest overlap with activation associated with blink suppression, as identified using general linear model analysis, demonstrating that activity associated with suppression can be determined without prior knowledge of task timings
How Early Trauma Shapes CEO Risk Appetite for Public Debt Versus Bank Debt
Get PDFThis study examines the impact of CEOs’ early disaster experiences on the choice of debt structure. We find that firms led by CEOs who have endured disasters are more inclined to shift from bank debt to public debt. This evidence remains robust across various alternative measures, empirical specifications, and identification tests aimed at mitigating endogeneity. The effect of CEOs’ early disaster experiences is more pronounced under specific institutional conditions. The effect strengthens with stricter regulatory oversight and lower unemployment risk, suggesting that institutional environments shape how personal experiences manifest in financial decisions. Overall, these findings suggest that the CEOs' inclination, shaped by early disasters, to take additional risk and seek greater autonomy, can have significant effects on corporate debt structure
Schrödinger's Cat and Digital Empathy: How Primary School Children Understand and Respond to Others' Feelings in Online Spaces
Get PDFChildren's digital and physical worlds are increasingly entwined as they build and manage meaningful connections online. Central to this is digital empathy and responsible online conduct, that is, a digital ethics of care. We focus on 10–11-year-old children from a primary school in the UK, exploring how they conceptualise and understand the feelings and behaviours of others. Children interviewed each other in pairs (N = 18) following school-based education regarding interviewing skills. Thematic analysis illustrated three themes related to digital empathy and interpretation focused on the discussion of an imaginary experiment of Schrödinger's cat, as an analogy for digital empathy. This analogy encompassed a finding that in digital environments, consequences of negative behaviours for others are challenging to discern, in terms of effect and affect. The findings have implications for our understanding of digital empathy and the challenge of teaching children responsible conduct online
Investigation of thermal management performance of electronic devices with phase change materials and pin fin heat sinks under periodic heating and cooling cycles
No full textEffective thermal management is critical for high-power devices such as metal–oxide–semiconductor field-effect transistors, as excessive heat can degrade their performance and reliability. Existing studies often simplify the heat source as a region of constant power, overlooking the effects of periodic thermal cycling. Moreover, there is a lack of investigation into heat accumulation under cyclic power loads, and comparisons of pin fin geometries frequently neglect volume consistency. This study addresses these gaps by developing a three-dimensional transient model of a SiC-based metal–oxide–semiconductor field-effect transistor system which can operate stably within 150 °C, incorporating a sinusoidal power load and material-specific heat generation zones. The thermal performance under varying phase change material types, pin fin shapes, and volume ratios was numerically evaluated. Results show that microencapsulated phase change materials reduced the average temperature by 15.7 %, and adding expanded graphite improved temperature uniformity, lowering the peak temperature difference by up to 36.9 °C, because the expanded graphite enhances the responsiveness of the phase change material to heating and cooling processes. Circular fins achieved the lowest average temperature at 121.9 °C, while a 12 % fin volume fraction further reduced temperature by 12.4 % and enhanced uniformity by 176.1 %. These results highlight an effective strategy for improving cooling in cyclic thermal environments
Cold Gas and Star Formation in the Phoenix Cluster with JWST
Get PDFWe present integral field unit observations of the Phoenix Cluster with the JWST Mid-infrared Instrument's Medium Resolution Spectrometer (MIRI/MRS). We focus this study on the molecular gas, dust, and star formation in the brightest cluster galaxy (BCG). We use precise spectral modeling to produce maps of the silicate dust, molecular gas, and polycyclic aromatic hydrocarbons (PAHs) in the inner ∼50 kpc of the cluster. We measure the optical depth from silicates by comparing the observed H 2 line ratios to those predicted by excitation models. We provide updated measurements of the total molecular gas mass of 1.9 +0.5 −0.4 × 10 10 M ⊙ , which agrees with CO-based estimates, providing an estimate of the CO-to-H 2 conversion factor of α CO = 0.8 ± 0.2 M ⊙ pc −2 (K km s −1) −1 ; an updated stellar mass of M * = 2.6 ± 0.5 × 10 10 M ⊙ ; and star formation rates averaged over 10 and 100 Myr of ⟨SFR⟩ 10 = 1340 ± 100 M ⊙ yr −1 and ⟨SFR⟩ 100 = 740 ± 80 M ⊙ yr −1 , respectively. The H 2 emission seems to be powered predominantly by shocks and star formation within the central ∼ 20 kpc, induced by stellar feedback and radio jets from the active galactic nucleus. Additionally, we find nearly an order of magnitude drop in the star formation rates estimated by PAH fluxes in cool core BCGs compared to field galaxies, suggesting that hot particles from the intracluster medium are destroying PAH grains even in the centralmost 10s of kpc
Ibrutinib and Rituximab versus Immunochemotherapy in previously untreated mantle cell lymphoma: a randomised open label phase II/III superiority trial
Get PDFBackgroundIbrutinib, a Bruton tyrosine kinase inhibitor, prolongs progression-free survival when added to immunochemotherapy as first line treatment. The ENRICH trial compared the chemotherapy-free combination of ibrutinib and the anti-CD20 antibody rituximab (ibrutinib–rituximab) with standard immunochemotherapy (R-CHOP [rituximab–cyclophosphamide, doxorubicin, vincristine, and prednisolone] or bendamustine–rituximab) in patients 60 years and older with untreated mantle-cell lymphoma.MethodsThis randomised, open-label, phase 2/3 superiority trial was performed at 66 sites in the UK, Sweden, Norway, Finland, and Denmark. Patients 60 years and older with untreated mantle-cell lymphoma (Ann–Arbor stage II–IV disease, an Eastern Cooperative Oncology Group performance-status score of 0–2) were randomly assigned to receive either rituximab plus immunochemotherapy or ibrutinib–rituximab in a 1:1 ratio, stratified by investigator choice of immunochemotherapy. Patients randomly allocated to the ibrutinib–rituximab (intervention) group received 560 mg oral ibrutinib daily in combination with six to eight cycles of 375 mg/m2 intravenous rituximab on day 1 of each cycle in the matched schedule of the pre-randomisation choice of immunochemotherapy (every 21 days for R-CHOP or every 28 days for rituximab–bendamustine). R-CHOP comprised 750 mg/m2 of cyclophosphamide, 50 mg/m2 of doxorubicin, and 1·4 mg/m2 vincristine on day 1 of each 21-day cycle, with 100 mg prednisolone on days 1–5 of each cycle. Rituximab–bendamustine comprised 90 mg/m2 of bendamustine on days 1 and 2 of each cycle, in combination with 375 mg/m2 rituximab on day 1 of each cycle. All responding patients in both groups at the end of induction received maintenance rituximab administered every 8 weeks for 2 years, and patients allocated to the intervention group continued ibrutinib until disease progression or unacceptable toxicity. The primary outcome was investigator-assessed progression-free survival, stratified by immunochemotherapy choice and analysed in the intention-to-treat population. The trial was registered with EudraCT (2015–000832–13) and is closed for recruitment.FindingsBetween Feb 15, 2016, and June 30, 2021, 397 patients were randomly allocated to immunochemotherapy (control) or ibrutinib–rituximab (intervention). Of the 397, 107 (27%) were pre-allocated to the immunochemotherapy choice of R-CHOP and 290 (73%) were pre-allocated to rituximab–bendamustine. In total, 198 were allocated to the control group (53 to R-CHOP and 145 to bendamustine–rituximab) and 199 were allocated to intervention. The median age was 74 years (IQR 70–77) for the intervention group and 74 years (70–78) in the control group. 296 patients (75%) were male and 101 patients (25%) were female; ethnicity data were not collected. At a median follow-up of 47·9 months, the median progression-free survival of ibrutinib–rituximab was superior to immunochemotherapy, with an adjusted hazard ratio (HR) of 0·69 (95% CI 0·52–0·90); p=0·0034. For those with pre-randomisation choice R-CHOP, the HR was 0·37 (0·22–0·62), and with bendamustine–rituximab, the HR was 0·91 (0·66–1·25). Across induction and maintenance, 67% of patients assigned to ibrutinib–rituximab and 70% of patients receiving immunotherapy reported grade 3 or above adverse events.InterpretationTo our knowledge, this is the first randomised trial in untreated mantle-cell lymphoma to demonstrate significant improvement in progression-free survival for ibrutinib–rituximab compared to immunochemotherapy. This study suggests that ibrutinib–rituximab should be considered a new standard of care option for first-line treatment of older patients with mantle-cell lymphoma
Challenges in the Diagnosis of Biliary Stricture and Cholangiocarcinoma and Perspectives on the Future Applications of Advanced Technologies
Get PDFIn the management of cholangiocarcinoma, effective biliary drainage and accurate diagnosis are vital to allow further treatment. Confirmation of tissue diagnosis and molecular characterization is also required to guide future treatment options including surgery and chemotherapy as well as the possible use of personalized treatments that target specific mutations present within individual tumours. Initial CT or MRI scans may be followed by endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) to obtain tissue samples. However, these methods often fall short due to difficulty in accessing entire bile duct strictures. SpyGlass cholangioscopy can improve diagnosis, yet may fail to provide sufficient tissue for molecular characterization. Here we present a perspective on the development of snake-like agile robots with integrated optical imaging and Raman spectroscopy. These robots could improve the mapping of the biliary tree and the precision of biopsy collection and allow tissue analysis in situ, as well as facilitating stenting to restore the flow of bile. A multidisciplinary approach that brings together clinicians, pathologists, and engineers is required to develop these new robotic technologies and improve patient outcomes
The Zwicker tone as a model to investigate auditory processing and tinnitus: a scoping review
Get PDFThe Zwicker tone (ZT) is an auditory illusion experienced by about 50% of the population immediately following a presentation of notched noise (NN). It is a faint, quickly decaying pure tone, the frequency of which falls within the range of the notch. Interestingly, although only half of the general population can perceive ZTs, one study has shown that almost everyone with tinnitus can perceive them. If there is this strong association, the ZT is an easily controllable paradigm that can be employed in the laboratory setting to explore tinnitus related concepts and better interrogate underlying neural mechanisms. This scoping review aimed to catalogue what is currently known about the ZT, and what can be said about its potential relationship with tinnitus. Through a systematic search of the literature, 16 records were identified for inclusion; all reported investigations of ZTs arising after spectrally contrasted in adults who had either normal hearing or tinnitus with/without hearing loss. The proportion of a given sample who were able to hear ZTs varied across studies, from 30 to 100%. The probability of hearing a ZT is modulated by a range of parameters, including: stimulus type (e.g., low-pass versus notched noise), notch centre frequency/width, and stimulus duration. Although these factors modulate the probability of perceiving a ZT, the idea that ZT perception is largely binary is also somewhat supported by individual data. In addition, some variables alter the quality of the percept, e.g., louder stimuli induce a higher pitched ZT. Despite several records drawing comparison between ZT and tinnitus, only one study has thus far investigated ZT in people with tinnitus, albeit finding a highly significant difference in responder rate in tinnitus versus control participants. Several methodological issues potentially affecting responder rate were identified, however, which warrants replication and extension, with careful control. We conclude that (1) Zwicker tone perception relies on a range of factors both stimulus and cognitive related, (2) Further work is required to map the parameters that induce the Zwicker tone and (3) While obvious similarities exist linking tinnitus and Zwicker tones more work is needed to prove the link between the two
Solidarity Cities: Confronting Racial Capitalism, Mapping Transformation, by Maliha Safri, Marianna Pavlovskaya, Stephen Healy and Craig Borowiak
No full textPrinciples of Industry-Academic Partnerships Informed by Digital Mental Health Collaboration: Mixed Methods Study
Get PDFBackground:Cross-sector collaboration is increasingly recognized as essential for addressing complex health challenges, including those in mental health. Industry-academic partnerships play a vital role in advancing research and developing health solutions, yet differing priorities and perspectives can make collaboration complex.Objective:This study aimed to identify key principles to support effective industry-academic partnerships, from the perspective of industry partners, and develop this into actionable guidance, which can be applied across sectors. Mental health served as a motivating example due to its urgent public health relevance and the growing role of digital innovation.Methods:Using a 3-stage, mixed-methods approach, we conducted a web-based survey of UK-based digital mental health companies (N=22) to identify key barriers and facilitators to industry-academic partnerships. This was followed by 2 focus groups (n=5) that explored emerging themes from the survey using thematic analysis. Finally, we conducted a workshop with industry representatives, researchers, clinicians, and PPI members to co-develop the Principles of Industry-Academic Partnerships (PIP) guidance.Results:Survey findings highlighted that industry partners valued academic collaboration for enhancing credibility, facilitating knowledge transfer, and gaining access to PPI networks. However, key barriers included high costs, slow academic timelines, and complex contracting processes. The 4 major themes that emerged from the focus groups were: advantages of collaboration, cultural differences between organizations, collaboration models, and structural barriers within universities. Through informed discussions in the workshop, these themes were explored, leading to the development of 14 actionable strategies. These strategies reflect industry perspectives and formed the PIP guidance, categorized under project initiation, defining the scope and agreements, project execution, and promoting sustainability.Conclusions:The PIP guidance provides a practical framework to support more effective and mutually beneficial collaborations between industry and academia. Developed through the lens of mental health research, the strategies identified are broadly applicable across disciplines where cross-sector partnerships are essential. Industry partners valued academic collaborations for their credibility and scientific rigor, but highlighted persistent structural and cultural barriers within universities. Addressing these challenges by aligning expectations and timelines, adopting flexible collaboration models, and streamlining operational processes can help foster impactful and sustainable partnerships in mental health and beyond
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