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Unit Root Tests for Explosive Financial Bubbles in the Presence of Deterministic Level Shifts
Get PDFThis article considers the issue of testing for an explosive bubble in financial time series in the presence of deterministic level shifts. We demonstrate that the sign-based variants of the Phillips-Shi-Yu test retain their asymptotic validity in the presence of level shifts under a weak restriction on the number of shifts that occur. This is in contrast to the original Phillips-Shi-Yu test which only remains valid under a joint restriction involving both the number and magnitudes of the level shifts. We find, through Monte Carlo simulation, that the original test can display substantial over-size in the presence of level shifts, without a corresponding increase in power, while the sign-based variants are largely unaffected in both regards. The sign-based tests therefore offer robust and powerful methods for detecting an explosive autoregressive regime in a financial time series that potentially contains level shifts. Empirical applications of the different tests are provided using intraday Bitcoin log price data and daily Nasdaq price data
Culture and Sketching: Comparative Analysis of UK and Chinese Designers
Get PDFThis research investigates the influence of culture on sketching by comparing UK and Chinese designers. We employed a novel dual-method approach: machine learning algorithms analyzed a dataset of 2,090 digitized sketches from student designers, while protocol analysis based on shape transformation rules examined the sketching processes of professional designers from both cultures. The machine learning analysis classified sketches by extracting region- and shape-based features, revealing distinctive visual attributes between the two cultures. Concurrently, protocol studies of professional designers' sketches uncovered patterns in their sketching processes. By integrating computational analyses of student sketches with protocol studies of professional designers, we identified significant cultural differences in both visual attributes and sketching processes. The paper discusses potential factors contributing to these disparities, drawing on insights from cross-cultural comparisons of cognitive styles. This comprehensive mixed-methods analysis provides new insights into the complex interplay between culture, cognition, and design
Gradient-constrained algorithm for simulating bubble growth in microchannel boiling flow using volume of fluid method
Get PDFThis study focuses on the numerical simulation of bubble growth in microchannels and addresses the interfacial deformations associated with phase transitions in the Volume of Fluid (VOF) method. In order to avoid the blurred deformation of the interface during bubble growth, a gradient-constrained algorithm is proposed to simulate bubble growth with sharp interface. The algorithm proposed in this paper is to compress the phase interface by selecting a suitable gradient range of the gas phase volume share change, and then adjust the position of the gas phase mass source to the compressed interface. It is recommended that the selected minimum value of the gas phase volume fraction gradient mode value falls between 20 % and 50 % of the maximum value. The proposed method is verified by three engineering problems: bubble growth in the microchannel, Taylor bubble movement in the microchannel and bubbles side-by-side rise and coalescing. The simulation results of these three engineering problems show good agreement with other researchers' simulation, theoretical model and experimental results. The algorithm proposed in this paper is more convenient in capturing the phase interface and describing the evaporation process
Using Oscillation to Improve the Insertion Depth and Consistency of Hollow Microneedles for Transdermal Insulin Delivery with Mechanistic Insights
Get PDFMicroneedles (MNs) offer the potential for discrete and painless transdermal drug delivery, yet poor insertion and dosing consistency have hindered their clinical translation. Specifically, hollow MNs are appropriate for the administration of liquid modalities, including insulin, which could prove to be beneficial for patients with type 1 diabetes mellitus. This work aimed to design and manufacture a hollow MN with an improved insertion and delivery profile suitable for insulin administration. Ex vivo insertion studies demonstrated that oscillation of MNs upon insertion into skin produced a favorable insertion profile, with reduced variation, compared to static MN insertion. Histological staining showed that this could be due to the repeated motion of the oscillating MN disrupting elastic fibers in the dermis. Additionally, permeation studies demonstrated that increased quantities of insulin were able to permeate the skin when oscillation was employed compared to static MN insertion. This study has shown that oscillation is a valuable tool in improving the transdermal delivery of insulin via a single hollow MN in vitro. Moving forward, in vivo studies should be completed to gain a fuller understanding of the benefits of the oscillation of MNs on transdermal drug delivery
Recombinant Human Tissue Kallikrein-1 for Treating Acute Ischemic Stroke and Preventing Recurrence
Get PDFNovel strategies are needed for the treatment of acute ischemic stroke when revascularization therapies are not clinically appropriate or are unsuccessful. Recombinant human tissue kallikrein-1 (rKLK1), a bradykinin-producing enzyme, offers a promising potential solution. In animal studies of acute stroke, there is a marked 36-fold increase in bradykinin B2 receptor on brain endothelial cells of the ischemic region. Due to this environment, rKLK1 generated bradykinin will exert a potent local vasodilation and increase brain perfusion via three synergistic signaling pathways downstream to the B2 receptor. Because of its preferential effect on ischemic tissue, systemic adverse effects such as hypotension are avoided with proper dosing. In addition, with initial vasodilation through recruitment of preexisting collaterals, rKLK1 promotes long-term benefit of brain perfusion by promoting new collateral formation. With an extended course of therapy for weeks after acute ischemic stroke, these multifaceted effects may also reduce the risk of stroke recurrence. A prior phase II trial demonstrated a favorable impact on clinical outcomes and recurrent strokes, particularly among patients who were not eligible for mechanical thrombectomy. A Phase II/III trial has launched in this population, though opportunities for combination for revascularization therapies deserve further investigation
A Qualitative Systematic Review of Barriers and Facilitators to Hepatitis B and C Programmes in Prisons
Get PDFThe prevalence of viral hepatitis amongst people in prisons is higher than in the general population. Screening, treatment, and vaccination programmes exist within prisons to reduce the incidence of hepatitis, although lower uptake has often been reported compared to similar programmes outside of prisons. We conducted a systematic review of qualitative evidence to explore the barriers and facilitators to hepatitis B and C reduction programmes in prisons from the perspectives of people in prison, custodial staff, and prison healthcare staff. Comprehensive searches of 5 databases were conducted in November 2023 and 28 studies included in the review. Four synthesised findings were identified: i) accurate, up-to-date knowledge of viral hepatitis disease and treatment amongst people in prison and staff is a facilitator to programme uptake, particularly when imparted by a trusted source, ii) personal subjective and relative views have a bearing on participation with the programme, iii) social interactions and relationships both within the community of people in prison and between them and staff groups influence participation in the programmes, and iv) the organisational structure of the prison and healthcare services within it affected programme participation. Recommendations derived from these findings are given to adapt viral hepatitis programmes for individual custodial settings thereby improving equitable programme access and hepatitis B and C reduction in this complex environment
Characterization of damage in galling testing of austenitic stainless steel as a function of pressure and sliding distance
Get PDFIt is well known that stainless steel is prone to galling, and in previous work, we have demonstrated that the degree of damage following galling tests in such materials is a function of both contact pressure and sliding distance. However, it is not clear if the same mechanisms operate across such tests. In the present work, the damage associated with galling of dissimilar stainless steel pairs (304 vs 316 pairs) as a function of contact pressure and sliding distance has been characterised. Tests utilised pairs in accord with the ASTM G196 geometry; contact pressures between 5 MPa and 50 MPa were employed with a range of sliding distances with the torque required for rotation being measured during the tests. Damage was characterized by profilometry, X-ray diffraction (XRD), and microscopy (including EBSD) of both the damaged surfaces and of cross-sections through damaged surfaces. It was shown that whilst the deformation-induced transformation to martensite occurred in all cases, it could not readily be used as a measure of galling intensity. However, the surface roughness (Sz) values increased with sliding distance across the range of contact pressure, with those at the higher contact pressure being significantly larger. The work provides new insights into the progression of wear and damage which results in what is termed 'galling' in a system which is prone to this. In particular, across the range of pressures examined, gross severe adhesive wear or 'galling' was observed to occur if the sliding distance is large enough; as such, it is argued that galling is simply a particular progression of adhesive wear often seen in severe sliding wear that has become gross enough to be visible by unassisted observation alone
The Linear Association of Chest Radiograph Opacification With Both Respiratory Physiology and Systemic Inflammation in Hospital In-Patients With Covid-19 Infection
Get PDFBackground: Chest radiographs are generally used for diagnostic purposes. They also have potential to quantify disease severity. This analysis tested the hypothesis that there was an association between chest radiograph opacification and measures of respiratory physiological status and systemic inflammation in patients with Covid-19 infection. Methods: Data on chest radiograph opacification were compared with concurrent measures of oxygen requirements and saturation and serum C-reactive protein. Results: Data were available from 628 individuals. The median opacification on chest radiographs was 20% (interquartile range 5–45). This was associated both SFR (oxygen saturation/supplementary oxygen) with an r value of −0.38 (95% confidence intervals CI: −0.45 to −31, Pearson's correlation coefficient) and CRP (+0.33; 95% CI: +0.24 to +0.41, Pearson's correlation coefficient). Conclusion: Chest radiograph opacification scores are associated with both respiratory physiology status and systemic inflammation levels in patients with Covid-19 infection
The importance of central sensitization for clinical trials of Disease Modifying Osteoarthritis drugs (DMOADs)
Get PDFOsteoarthritis (OA) pain is associated with structural changes in the joint, which are usually quantified by imaging techniques. It is anticipated that structural disease modifying OA drugs (DMOADs) would reduce the burden of OA pain. However, nociceptive pain is moderated by the central nervous system. Central sensitization, increased activity in central nervous system neurones in response to a standard nociceptive input, is one reason why disease modification might not effectively relieve OA pain. Central sensitization may result from facilitated central neuronal activity, or inadequate inhibition by endogenous analgesic mechanisms. It changes the experience of pain: its severity, distribution and qualities, and its emotional and cognitive dimensions. Central sensitization can be a barrier to analgesic benefit from treatments directed at joint structure, and central pain processing can obscure analgesic benefit from structural modification in randomised controlled trials. Indices of central pain hypersensitivity might reflect central sensitization in humans. They include self-report questionnaires such as the Central Aspects of Pain (CAP) and short form Central Sensitization Inventory (CSI-9), and quantitative sensory testing (QST) modalities of Pressure Pain detection Thresholds distant to the affected joint, Temporal Summation, and Conditioned Pain Modulation. Understanding, measuring, managing and adjusting for central pain hypersensitivity should increase the power of clinical trials to demonstrate that DMOADs not only improve joint imaging outcomes, but also improve pain, the predominant clinical problem of OA
Central aspects of pain associated with physical activity: results from the Investigating Musculoskeletal Health and Wellbeing cohort
Get PDFBackground:Knee pain reduces activity, while inactivity can increase pain. The central nervous system modulates both pain and activity. The 8-item Central Aspects of Pain (CAP) questionnaire measures self-reported symptoms associated with current and future knee pain severity and psychophysical evidence of central pain sensitivity. The objective was to explore associations between CAP and physical inactivity in people with knee pain.MethodsParticipants from the Investigating Musculoskeletal Health and Wellbeing cohort who reported their knee as their most troublesome joint with numerical rating scale pain severity ≥1/10 completed questionnaires at baseline and 12-months addressing demographic and clinical characteristics, CAP questionnaire and physical inactivity (Frail Non-Disabled (FiND) questionnaire item). Chi-squared, correlations and multivariable logistic regression were performed.Results:722 participants provided baseline and 404 longitudinal data. Higher baseline CAP scores were associated with higher baseline pain severity (OR 1.25 (95%CI 1.02, 1.53) p=0.032) and physical inactivity (OR 1.18 (95%CI 1.11, 1.25) p<0.001). Increasing CAP scores over 12 months were associated with becoming physically inactive (OR 1.16 (95%CI 1.01, 1.32) p=0.032). The effects of CAP on physical inactivity were not fully explained by pain severity, nor by any single characteristic of widespread pain distribution, emotional or cognitive factors, sleep disturbance or fatigue.Conclusions:CAP displays cross-sectional and longitudinal associations with physical inactivity. Central nervous system manifestations of pain appear to link pain with physical activity and may be more important than pain severity
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