• Off the couch: a psychiatrist’s candid stories of hope and healing

      Loewenthal, Kate Miriam; orcid: 0000-0001-7667-7809 (Informa UK Limited, 2021-07-09)
    • Off the couch: a psychiatrist’s candid stories of hope and healing

      Loewenthal, Kate Miriam; orcid: 0000-0001-7667-7809 (Informa UK Limited, 2021-07-09)
    • Older adults’ construal of sedentary behaviour: Implications for reducing sedentary behaviour in older adult populations

      McGowan, Laura J; orcid: 0000-0002-4054-9300; email: laura.mcgowan@manchester.ac.uk; Powell, Rachael; French, David P; orcid: 0000-0002-7663-7804 (SAGE Publications, 2020-03-01)
      Older adults are the most sedentary age group, with sedentary behaviour having negative health-related consequences. There is currently limited understanding of how older adults view sedentary behaviour. This study investigated older adults’ understanding of the concept of sedentary behaviour. Semi-structured interviews were conducted with 22 community-dwelling older adults in urban North-West England, selected to be diverse in socio-economic background and activity levels. Interviews were recorded and transcribed verbatim. An inductive thematic analysis was conducted. Participants often construed sedentary behaviour as synonymous with a lack of physical activity, and many perceived reducing sedentary behaviour and increasing moderate-to-vigorous physical activity to be the same thing. Participants perceived the term ‘sedentary’ to have negative connotations and were often judgemental of people who engaged in high levels of sedentary behaviour. Most participants considered reducing sedentary behaviour to be of value, though more active individuals were unconvinced that reducing sedentary behaviour has value beyond the benefits of being physically active. Interventions may wish to provide education to address the misconception that increasing moderate-to-vigorous physical activity is necessary in order to reduce sedentary behaviour. Educating older adults on the independent health consequences of sedentary behaviour may also prove beneficial.
    • On the Derivation of Multisymplectic Variational Integrators for Hyperbolic PDEs Using Exponential Functions

      Kosmas, Odysseas; orcid: 0000-0002-7047-9438; email: odysseas.kosmas@manchester.ac.uk; Boom, Pieter; orcid: 0000-0001-7437-277X; email: pieter.boom@manchester.ac.uk; Jivkov, Andrey P.; orcid: 0000-0002-3454-7341; email: andrey.jivkov@manchester.ac.uk (MDPI, 2021-08-25)
      We investigated the derivation of numerical methods for solving partial differential equations, focusing on those that preserve physical properties of Hamiltonian systems. The formulation of these properties via symplectic forms gives rise to multisymplectic variational schemes. By using analogy with the smooth case, we defined a discrete Lagrangian density through the use of exponential functions, and derived its Hamiltonian by Legendre transform. This led to a discrete Hamiltonian system, the symplectic forms of which obey the conservation laws. The integration schemes derived in this work were tested on hyperbolic-type PDEs, such as the linear wave equations and the non-linear seismic wave equations, and were assessed for their accuracy and the effectiveness by comparing them with those of standard multisymplectic ones. Our error analysis and the convergence plots show significant improvements over the standard schemes.
    • On the Geometric Description of Nonlinear Elasticity via an Energy Approach Using Barycentric Coordinates

      Kosmas, Odysseas; orcid: 0000-0002-7047-9438; email: odysseas.kosmas@manchester.ac.uk; Boom, Pieter; email: pieter.boom@manchester.ac.uk; Jivkov, Andrey P.; orcid: 0000-0002-3454-7341; email: andrey.jivkov@manchester.ac.uk (MDPI, 2021-07-19)
      The deformation of a solid due to changing boundary conditions is described by a deformation gradient in Euclidean space. If the deformation process is reversible (conservative), the work done by the changing boundary conditions is stored as potential (elastic) energy, a function of the deformation gradient invariants. Based on this, in the present work we built a “discrete energy model” that uses maps between nodal positions of a discrete mesh linked with the invariants of the deformation gradient via standard barycentric coordinates. A special derivation is provided for domains tessellated by tetrahedrons, where the energy functionals are constrained by prescribed boundary conditions via Lagrange multipliers. The analysis of these domains is performed via energy minimisation, where the constraints are eliminated via pre-multiplication of the discrete equations by a discrete null-space matrix of the constraint gradients. Numerical examples are provided to verify the accuracy of the proposed technique. The standard barycentric coordinate system in this work is restricted to three-dimensional (3-D) convex polytopes. We show that for an explicit energy expression, applicable also to non-convex polytopes, the general barycentric coordinates constitute fundamental tools. We define, in addition, the discrete energy via a gradient for general polytopes, which is a natural extension of the definition for discrete domains tessellated by tetrahedra. We, finally, prove that the resulting expressions can consistently describe the deformation of solids.
    • On Thresholds for Dynamic Strength in Solids

      Bourne, N. K.; orcid: 0000-0002-8883-1196; email: neil.bourne@manchester.ac.uk (Springer International Publishing, 2021-04-20)
      Abstract: The limits of elastic behaviour change with the nature of the impulse applied to a target and the size of volume interrogated by a measurement, since it is the pre-existing defects sampled within its rise that determine the response observed. This review considers a range of solids of different material classes and tracks the development of the strength of the material during shock loading, from yield at the Hugoniot elastic limit, across the weak shock regime, to its transition to strong shock behaviour. It is shown that at this stress, the weak shock limit (WSL), the shear component of the applied stress exceeds the theoretical strength of the material. Beyond this threshold, there are a number of new responses that confirm a transition from an inhomogeneous to a homogeneous state. Further, whilst strength rises across the weak shock regime, it saturates at the WSL. For instance, failure in shocked glasses transitions from localised fracture initiated at target boundaries to a global failure at this threshold at the theoretical strength. Sapphire′s strength asymptotes to the theoretical strength of the strongest direction in its lattice. Finally, the fourth-power dependence of strain rate upon stress appears to be a consequence of the homogeneous flow in the strong shock regime. This review suggests that µ/2π is a good approximation for the unrelaxed theoretical strength of solids at increasing stresses beyond the WSL. The methodology unfolded here represents a new means to experimentally determine the ultimate shear strength of solids.
    • On Thresholds for Dynamic Strength in Solids

      Bourne, N. K.; orcid: 0000-0002-8883-1196; email: neil.bourne@manchester.ac.uk (Springer International Publishing, 2021-04-20)
      Abstract: The limits of elastic behaviour change with the nature of the impulse applied to a target and the size of volume interrogated by a measurement, since it is the pre-existing defects sampled within its rise that determine the response observed. This review considers a range of solids of different material classes and tracks the development of the strength of the material during shock loading, from yield at the Hugoniot elastic limit, across the weak shock regime, to its transition to strong shock behaviour. It is shown that at this stress, the weak shock limit (WSL), the shear component of the applied stress exceeds the theoretical strength of the material. Beyond this threshold, there are a number of new responses that confirm a transition from an inhomogeneous to a homogeneous state. Further, whilst strength rises across the weak shock regime, it saturates at the WSL. For instance, failure in shocked glasses transitions from localised fracture initiated at target boundaries to a global failure at this threshold at the theoretical strength. Sapphire′s strength asymptotes to the theoretical strength of the strongest direction in its lattice. Finally, the fourth-power dependence of strain rate upon stress appears to be a consequence of the homogeneous flow in the strong shock regime. This review suggests that µ/2π is a good approximation for the unrelaxed theoretical strength of solids at increasing stresses beyond the WSL. The methodology unfolded here represents a new means to experimentally determine the ultimate shear strength of solids.
    • Online screencasting tutorials: A way forward for legal resources training?

      Peters, Lisa; University of Chester (Cambridge University Press, 2011)
      This journal articles discusses the using screencasting (video tutorials) in legal resources training.
    • Open questions in organic crystal polymorphism

      Cruz-Cabeza, Aurora J.; orcid: 0000-0002-0957-4823; email: aurora.cruzcabeza@manchester.ac.uk; Feeder, Neil; Davey, Roger J. (Nature Publishing Group UK, 2020-10-19)
      Polymorphs, crystals with different structure and properties but the same molecular composition, arise from the subtle interplay between thermodynamics and kinetics during crystallisation. In this opinion piece, the authors review the latest developments in the field of polymorphism and discuss standing open questions.
    • Opinion of the Scientific Committee on Consumer safety (SCCS) – Final Opinion on propylparaben (CAS No 94-13-3, EC No 202-307-7)

      Bodin, Laurent; Rogiers, Vera; Bernauer, Ulrike; Chaudhry, Qasim; Coenraads, Pieter Jan; orcid: 0000-0001-9458-7129; Dusinska, Maria; Ezendam, Janine; Gaffet, Eric; Galli, Corrado Ludovico; Granum, Berit; et al.
      In cosmetic products, the ingredient propylparaben (CAS No 94-13-3, EC No 202-307-7) with the chemical names Propyl 4-hydroxybenzoate and 4-Hydroxybenzoic acid propyl ester is currently regulated as a preservative in a concentration up to 0.14 % (as acid) (Annex V/12a). In addition, a safe concentration was established for mixtures of parabens, where the sum of the individual concentrations should not exceed 0.8 % (as acid). However, in such mixtures the sum of the individual concentrations of butyl- and propylparaben and their salts should not exceed 0.14 %. Propylparaben was subject to different safety evaluations in 2005 (SCCP/0874/05), 2006 (SCCP/1017/06), 2008 (SCCP/1183/08), 2010 (SCCS/1348/10), 2011 (SCCS/1446/11), 2013 (SCCS/1514/13). On the basis of the safety assessment of propylparaben, and considering the concerns related to potential endocrine disrupting properties, the SCCS has concluded that propylparaben is safe when used as a preservative in cosmetic products up to a maximum concentration of 0.14 %. The available data on propylparaben provide some indications for potential endocrine effects. However, the current level of evidence is not sufficient to regard it as an endocrine disrupting substance, or to derive a toxicological point of departure based on endocrine disrupting properties for use in human health risk assessment. The SCCS mandates do not address environmental aspects. Therefore, this assessment did not cover the safety of propylparaben for the environment.
    • Opportunity Costs Pacifism

      Pattison, James; orcid: 0000-0002-4649-358X; email: james.pattison@manchester.ac.uk (Springer Netherlands, 2020-05-26)
      Abstract: If the resources used to wage wars could be spent elsewhere and save more lives, does this mean that wars are unjustified? This article considers this question, which has been largely overlooked by Just War Theorists and pacifists. It focuses on whether the opportunity costs of war lead to a form of pacifism, which it calls ‘Opportunity Costs Pacifism’. The article argues that Opportunity Costs Pacifism is, at the more ideal level, compelling. It suggests that the only plausible response to Opportunity Costs Pacifism applies in highly nonideal circumstances. This has major implications for Just War Theory and pacifism since it is only at the highly nonideal level that war can be justified.
    • Optimising Large Animal Models of Sustained Atrial Fibrillation: Relevance of the Critical Mass Hypothesis

      Denham, Nathan C.; email: Nathan.denham@manchester.ac.uk; Pearman, Charles M.; Madders, George W. P.; Smith, Charlotte E. R.; Trafford, Andrew W.; Dibb, Katharine M. (Frontiers Media S.A., 2021-06-15)
      Background: Large animal models play an important role in our understanding of the pathophysiology of atrial fibrillation (AF). Our aim was to determine whether prospectively collected baseline variables could predict the development of sustained AF in sheep, thereby reducing the number of animals required in future studies. Our hypothesis was that the relationship between atrial dimensions, refractory periods and conduction velocity (otherwise known as the critical mass hypothesis) could be used for the first time to predict the development of sustained AF. Methods: Healthy adult Welsh mountain sheep underwent a baseline electrophysiology study followed by implantation of a neurostimulator connected via an endocardial pacing lead to the right atrial appendage. The device was programmed to deliver intermittent 50 Hz bursts of 30 s duration over an 8-week period whilst sheep were monitored for AF. Results: Eighteen sheep completed the protocol, of which 28% developed sustained AF. Logistic regression analysis showed only fibrillation number (calculated using the critical mass hypothesis as the left atrial diameter divided by the product of atrial conduction velocity and effective refractory period) was associated with an increased likelihood of developing sustained AF (Ln Odds Ratio 26.1 [95% confidence intervals 0.2–52.0] p = 0.048). A receiver-operator characteristic curve showed this could be used to predict which sheep developed sustained AF (C-statistic 0.82 [95% confidence intervals 0.59–1.04] p = 0.04). Conclusion: The critical mass hypothesis can be used to predict sustained AF in a tachypaced ovine model. These findings can be used to optimise the design of future studies involving large animals.
    • Optimising use of 4D-CT phase information for radiomics analysis in lung cancer patients treated with stereotactic body radiotherapy

      Davey, Angela; orcid: 0000-0002-8377-5113; email: angela.davey@postgrad.manchester.ac.uk; van Herk, Marcel; Faivre-Finn, Corinne; Brown, Sean; McWilliam, Alan (IOP Publishing, 2021-05-24)
      Abstract: Purpose. 4D-CT is routine imaging for lung cancer patients treated with stereotactic body radiotherapy. No studies have investigated optimal 4D phase selection for radiomics. We aim to determine how phase data should be used to identify prognostic biomarkers for distant failure, and test whether stability assessment is required. A phase selection approach will be developed to aid studies with different 4D protocols and account for patient differences. Methods. 186 features were extracted from the tumour and peritumour on all phases for 258 patients. Feature values were selected from phase features using four methods: (A) mean across phases, (B) median across phases, (C) 50% phase, and (D) the most stable phase (closest in value to two neighbours), coined personalised selection. Four levels of stability assessment were also analysed, with inclusion of: (1) all features, (2) stable features across all phases, (3) stable features across phase and neighbour phases, and (4) features averaged over neighbour phases. Clinical-radiomics models were built for twelve combinations of feature type and assessment method. Model performance was assessed by concordance index (c-index) and fraction of new information from radiomic features. Results. The most stable phase spanned the whole range but was most often near exhale. All radiomic signatures provided new information for distant failure prediction. The personalised model had the highest c-index (0.77), and 58% of new information was provided by radiomic features when no stability assessment was performed. Conclusion. The most stable phase varies per-patient and selecting this improves model performance compared to standard methods. We advise the single most stable phase should be determined by minimising feature differences to neighbour phases. Stability assessment over all phases decreases performance by excessively removing features. Instead, averaging of neighbour phases should be used when stability is of concern. The models suggest that higher peritumoural intensity predicts distant failure.
    • Optimising use of 4D-CT phase information for radiomics analysis in lung cancer patients treated with stereotactic body radiotherapy

      Davey, Angela; orcid: 0000-0002-8377-5113; email: angela.davey@postgrad.manchester.ac.uk; van Herk, Marcel; Faivre-Finn, Corinne; Brown, Sean; McWilliam, Alan (IOP Publishing, 2021-05-24)
      Abstract: Purpose. 4D-CT is routine imaging for lung cancer patients treated with stereotactic body radiotherapy. No studies have investigated optimal 4D phase selection for radiomics. We aim to determine how phase data should be used to identify prognostic biomarkers for distant failure, and test whether stability assessment is required. A phase selection approach will be developed to aid studies with different 4D protocols and account for patient differences. Methods. 186 features were extracted from the tumour and peritumour on all phases for 258 patients. Feature values were selected from phase features using four methods: (A) mean across phases, (B) median across phases, (C) 50% phase, and (D) the most stable phase (closest in value to two neighbours), coined personalised selection. Four levels of stability assessment were also analysed, with inclusion of: (1) all features, (2) stable features across all phases, (3) stable features across phase and neighbour phases, and (4) features averaged over neighbour phases. Clinical-radiomics models were built for twelve combinations of feature type and assessment method. Model performance was assessed by concordance index (c-index) and fraction of new information from radiomic features. Results. The most stable phase spanned the whole range but was most often near exhale. All radiomic signatures provided new information for distant failure prediction. The personalised model had the highest c-index (0.77), and 58% of new information was provided by radiomic features when no stability assessment was performed. Conclusion. The most stable phase varies per-patient and selecting this improves model performance compared to standard methods. We advise the single most stable phase should be determined by minimising feature differences to neighbour phases. Stability assessment over all phases decreases performance by excessively removing features. Instead, averaging of neighbour phases should be used when stability is of concern. The models suggest that higher peritumoural intensity predicts distant failure.
    • Optimization of competitive supply chains with retailers' horizontal cooperation and consumers' green preference.

      Shang, Wenfang; Teng, Liangliang; Yang, Jian-Bo; email: jian-bo.yang@manchester.ac.uk (2021-07-16)
      With the wider recognition of the concept of environmental protection and sustainable development, more and more manufacturers have begun to implement green manufacturing strategies. However, green development is a gradual process, and the coexistence of ordinary and green products is common. This paper examines the competition between ordinary products and green ones based on supply chains, and discusses the impact of retailers' horizontal cooperation on pricing, greenness, market demand, profit, and other related decisions and results. Model solutions and numerical experiments have shown that consumers' green preference (CGP) has a positive impact on the results of green products and negative effects on those of ordinary ones; however, the impact of competition intensity (CI) is more complex, and the trend tends to change if it exceeds a certain critical value. In general, cooperation encourages retailers to raise prices and make manufacturers lower wholesale prices, but the retail and wholesale prices of green products are always higher than the corresponding prices of ordinary ones. Market demand can be reduced due to cooperation, but it is conducive to strengthening green products' greenness. However, if CI exceeds a certain threshold, the greenness will be weakened by cooperation. Both retailers can benefit from cooperation easily and they always reach a win-win situation, but manufacturers suffer badly as a result. Nevertheless, when CI is weak, cooperation will bring a greater profit improvement to the whole chain of ordinary products; in this case, if a retailer is willing to compensate for a manufacturer's profit loss and help it benefit from cooperation, the manufacturer will encourage the retailer to cooperate horizontally with the green retailer, but the green chain will be seriously damaged. When CI is strong, the greenness of green products is not obvious enough, and cooperation can bring some chances to achieve a win-win situation for two chains; if the green retailer can obtain a larger share from cooperation under this scenario, it can also enable its manufacturer to obtain compensation and change the profit increment from negative to positive. From an overall perspective, when CI is very weak or very strong, horizontal cooperation is conducive to improving the profit of the entire supply chain competition system, but when CI is relatively flat, independent operation for each chain is more advantageous; if the competition status is stable and unchanged, independent competition will be superior to horizontal cooperation. [Abstract copyright: © 2021. The Author(s).]
    • Optimization of Glass Transition Temperature and Pot Life of Epoxy Blends Using Response Surface Methodology (RSM)

      Junid, Ramli; email: ramli@ump.edu.my; Siregar, Januar Parlaungan; orcid: 0000-0002-8130-1168; email: januar@ump.edu.my; Endot, Nor Azam; orcid: 0000-0002-8424-4971; email: e_norazam@upm.edu.my; Razak, Jeefferie Abd; orcid: 0000-0002-0318-4541; email: jeefferie@utem.edu.my; Wilkinson, Arthur N.; orcid: 0000-0001-8856-3219; email: arthur.wilkinson@manchester.ac.uk (MDPI, 2021-09-27)
      The aim of this work was to improve the processability of triglycidyl-p-aminophenol (TGPAP) epoxy resin. To achieve this improvement, a diluent, the diglycidyl ether of bisphenol F (DGEBF or BPF), was added to TGPAP, and the blended epoxy was then cured with 4, 4′-diaminodiphenyl sulfones (DDS). A response surface methodology (RSM) was used, with the target response being to achieve a blended resin with a high glass transition temperature (Tg) and maximum pot life (or processing window, PW). Characterization through dynamic mechanical thermal analysis (DMTA) and using a rheometer indicated that the optimum formulation was obtained at 55.6 wt.% of BPF and a stoichiometric ratio of 0.60. Both values were predicted to give Tg at 180 °C and a processing window of up to 136.1 min. The predicted values were verified, with the obtained Tg and processing window (PW) being 181.2 ± 0.8 °C and 140 min, respectively, which is close to the values predicted using the RSM.
    • Optimization of quantitative susceptibility mapping for regional estimation of oxygen extraction fraction in the brain

      McFadden, John J.; orcid: 0000-0002-3034-6622; email: john.mcfadden@postgrad.manchester.ac.uk; Matthews, Julian C.; Scott, Lauren A.; orcid: 0000-0002-5423-0042; Parker, Geoff J. M.; orcid: 0000-0003-2934-2234; Lohézic, Maélène; Parkes, Laura M.; orcid: 0000-0001-6488-507X (2021-03-29)
      Purpose: We sought to determine the degree to which oxygen extraction fraction (OEF) estimated using quantitative susceptibility mapping (QSM) depends on two critical acquisition parameters that have a significant impact on acquisition time: voxel size and final echo time. Methods: Four healthy volunteers were imaged using a range of isotropic voxel sizes and final echo times. The 0.7 mm data were downsampled at different stages of QSM processing by a factor of 2 (to 1.4 mm), 3 (2.1 mm), or 4 (2.8 mm) to determine the impact of voxel size on each analysis step. OEF was estimated from 11 veins of varying diameter. Inter‐ and intra‐session repeatability were estimated for the optimal protocol by repeat scanning in 10 participants. Results: Final echo time was found to have no significant effect on OEF. The effect of voxel size was significant, with larger voxel sizes underestimating OEF, depending on the proximity of the vein to the superficial surface of the brain and on vein diameter. The last analysis step of estimating vein OEF values from susceptibility images had the largest dependency on voxel size. Inter‐session coefficients of variation on OEF estimates of between 5.2% and 8.7% are reported, depending on the vein. Conclusion: QSM acquisition times can be minimized by reducing the final echo time but an isotropic voxel size no larger than 1 mm is needed to accurately estimate OEF in most medium/large veins in the brain. Such acquisitions can be achieved in under 4 min.
    • Oral Ferric Maltol Does Not Adversely Affect the Intestinal Microbiome of Patients or Mice, but Ferrous Sulphate Does

      Mahalhal, Awad; orcid: 0000-0001-6925-5018; email: awad.mahalhal@liverpool.ac.uk; Frau, Alessandra; email: A.Frau@liverpool.ac.uk; Burkitt, Michael D.; orcid: 0000-0002-5055-6408; email: michael.burkitt@manchester.ac.uk; Ijaz, Umer Z.; orcid: 0000-0001-5780-8551; email: Umer.Ijaz@glasgow.ac.uk; Lamb, Christopher A.; email: christopher.lamb@newcastle.ac.uk; Mansfield, John C.; orcid: 0000-0003-2490-7750; email: john.mansfield8@btinternet.com; Lewis, Stephen; email: sjl@doctors.org.uk; Pritchard, D. Mark; orcid: 0000-0001-7971-3561; email: dmpritch@liverpool.ac.uk; Probert, Chris S.; email: mdcsjp@liverpool.ac.uk (MDPI, 2021-06-30)
      Background and Aims: Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency. Methods: Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above). Results: In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS. Conclusions: This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.
    • Organic and inorganic equivalent models for analysis of red blood cell mechanical behaviour.

      Atifeh, Seid Mohammad; Davey, Keith; Sadeghi, Hamed; Darvizeh, Rooholamin; email: rooholamin.darvizeh@manchester.ac.uk; Darvizeh, Abolfazl (2021-09-30)
      Experimental investigation into the mechanical response of red blood cells is presently impeded with the main impediments being the micro dimensions involved and ethical issues associated with in vivo testing. The widely employed alternative approach of computational modelling suffers from its own inherent limitations being reliant on precise constitutive and boundary information. Moreover, and somewhat critically, numerical computational models themselves are required to be validated by means of experimentation and hence suffer similar impediments. An alternative experimental approach is examined in this paper involving large-scale equivalent models manufactured principally from inorganic, and to lesser extent organic, materials. Although there presently exists no known method providing the means to investigate the mechanical response of red blood cells using scaled models simultaneously having different dimensions and materials, the present paper aims to develop a scaled framework based on the new finite-similitude theory that has appeared in the recent open literature. Computational models are employed to test the effectiveness of the proposed method, which in principle can provide experimental solution methods to a wide range of practical applications including the design of red-blood cell nanorobots and drug delivery systems. By means of experimentally validated numerical experiments under impact loading it is revealed that although exact prediction is not achieved good accuracy can nevertheless be obtained. Furthermore, it is demonstrated how the proposed approach for first time provides a means to relate models at different scales founded on different constitutive equations. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors

      Stern, Peter L.; email: peter.stern@manchester.ac.uk; Dalianis, Tina; email: tina.dalianis@ki.se (MDPI, 2021-06-25)
      While head and neck squamous cell carcinomas (HNSCC) are marginally decreasing due to the reduction in exposure to the major risk factors, tobacco and alcohol, the incidence of high-risk human papillomavirus (HPV)-positive oropharynx squamous cell carcinomas (OPSCC), especially those in the tonsil and base of tongue subsites, are increasing. Patients with the latter are younger, display a longer overall survival, and show a lower recurrence rate after standard-of-care treatment than those with HPV-negative OPSCC. This may reflect an important role for immune surveillance and control during the natural history of the virally driven tumour development. Immune deviation through acquisition of immune-suppressive factors in the tumour microenvironment (TME) is discussed in relation to treatment response. Understanding how the different immune factors are integrated in the TME battleground offers opportunities for identifying prognostic biomarkers as well as novel therapeutic strategies. OPSCC generally receive surgery or radiotherapy for early-stage tumour treatment, but many patients present with locoregionally advanced disease requiring multimodality therapies which can involve considerable complications. This review focuses on the utilization of newly emerged immune checkpoint inhibitors (PD-1/PD-L1 pathway) for treatment of HNSCC, in particular HPV-positive OPSCC, since they could be less toxic and more efficacious. PD-1/PD-L1 expression in the TME has been extensively investigated as a biomarker of patient response but is yet to provide a really effective means for stratification of treatment. Extensive testing of combinations of therapeutic approaches by types and sequencing will fuel the next evolution of treatment for OPSCC.