• New singly and doubly even binary [72,36,12] self-dual codes from M 2(R)G - group matrix rings

      Korban, Adrian; orcid: 0000-0001-5206-6480; Şahinkaya, Serap; Ustun, Deniz; orcid: 0000-0002-5229-4018 (Elsevier, 2021-09-17)
      In this work, we present a number of generator matrices of the form [ I 2 n | τ 2 ( v ) ] , where I 2 n is the 2 n × 2 n identity matrix, v is an element in the group matrix ring M 2 ( R ) G and where R is a finite commutative Frobenius ring and G is a finite group of order 18. We employ these generator matrices and search for binary [ 72 , 36 , 12 ] self-dual codes directly over the finite field F 2 . As a result, we find 134 Type I and 1 Type II codes of this length, with parameters in their weight enumerators that were not known in the literature before. We tabulate all of our findings.
    • New Technique to Improve the Ductility of Steel Beam to Column Bolted Connections: A Numerical Investigation

      Shaheen, Mohamed A.; email: m.shaheen@lboro.ac.uk; Galal, Mohamed Ahmed; orcid: 0000-0003-4263-0361; email: mohamed1982dh@yahoo.com; Cunningham, Lee S.; orcid: 0000-0002-7686-7490; email: lee.scott.cunningham@manchester.ac.uk; Foster, Andrew S. J.; email: AWFR@cowi.com (MDPI, 2021-10-22)
      A novel method to improve the robustness of steel end plate connections is presented in this paper. Existing commonly adopted techniques alter the stiffness of the beam or the end plate to improve the connection’s robustness. In this study, the robustness is enhanced by improving the contribution of the bolts to the rotational capacity of connections; the higher the bolts’ elongation, the higher the rotational capacity that can be achieved. However, the brittleness of the bolt material, combined with its small length, results in negligible elongation. Alternatively, the load path between the end plate and the bolts can be interrupted with a ductile element to achieve the required elongation. This can be achieved by inserting a steel sleeve with a designated length, thickness, and wall curvature between the end plate and the washer. The proposed sleeve should be designed so that its ultimate capacity is less than the force in the bolt at failure; accordingly, the sleeve develops a severe bending deformation before the failure of any connection components. Using a validated finite element model, end plate connections with various parameters are numerically investigated to understand the performance of the sleeve device. The proposed system substantially enhances the rotational capacity of the connections, ranging between 1.37 and 2.46 times that of the standard connection. It is also concluded that the sleeved connections exhibit a consistent elastic response with the standard connections, indicating the proposed system is compatible with codified elastic design approaches without modification. Furthermore, for a specific connection, various ductile responses can be achieved without altering the connection capacity nor configuration.
    • Next steps in dermatology training: choosing to enter higher speciality training and the transition from trainee to consultant dermatologist

      Ashraf, I.; orcid: 0000-0002-7246-5451; Chowdhury, M. M. U.; Murphy, R.; Griffiths, T. W.; Esmail, A.; Young, H. S.; orcid: 0000-0003-1538-445X; email: helen.s.young@manchester.ac.uk (2021-01-17)
      Summary: Background: Junior doctors are required to make career decisions at an early stage in their postgraduate training. Trainees also feel inadequately prepared for the transition to consultant roles. Aim: To explore the key factors influencing the choice of dermatology as a postgraduate medical career and to identify the training needs required for transition from trainee to consultant. Methods: An online questionnaire was designed to identify (i) why trainees chose a postgraduate medical career in dermatology, and (ii) the training required for transition from trainee to consultant. Results: In total, 46 responses were received from trainees in their first to final years (ST3–6), of whom 89% had undertaken an undergraduate dermatology placement, with a median duration of 2 weeks. Dermatology was considered as a career during medical school by 61% of trainees, and 41% confirmed their decision to pursue a career in dermatology during foundation training. The most influential factors involved in speciality selection were first, enjoyment of the work, second, postgraduate experience and equal third, the variety of the speciality and the regularity of working hours (P < 0.05). Mentoring was pivotal to career decision‐making. Significant numbers of trainees expressed a need for training in medical leadership, such as running an outpatient clinic and supervising clinical multidisciplinary teams. Although larger numbers of trainees had training in management of dermatology services, such as service improvement (52%) and local governance/National Health Service structures (43%), significant numbers of trainees had no training in writing job plans (89%) or business plans (85%). Training was significantly deficient for personal management and self‐awareness. Conclusion: Our study highlights important considerations in career decision‐making for trainees. Training in medical leadership, management and self‐awareness could be enhanced to ensure that trainees feel adequately equipped for consultant roles.
    • Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila

      Giachello, Carlo N. G.; Fan, Yuen Ngan; Landgraf, Matthias; Baines, Richard A.; email: Richard.Baines@manchester.ac.uk (Nature Publishing Group UK, 2021-10-13)
      Abstract: The emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are not well understood. In particular, the mechanisms that transduce neuronal activity to regulating changes in neuronal physiology or structure are not known. Here, we take advantage of a recently identified invertebrate model for studying critical periods, the Drosophila larval locomotor system. Manipulation of neuronal activity during this critical period is sufficient to increase synaptic excitation and to permanently leave the locomotor network prone to induced seizures. Using genetics and pharmacological manipulations, we identify nitric oxide (NO)-signaling as a key mediator of activity. Transiently increasing or decreasing NO-signaling during the critical period mimics the effects of activity manipulations, causing the same lasting changes in synaptic transmission and susceptibility to seizure induction. Moreover, the effects of increased activity on the developing network are suppressed by concomitant reduction in NO-signaling and enhanced by additional NO-signaling. These data identify NO signaling as a downstream effector, providing new mechanistic insight into how activity during a critical period tunes a developing network.
    • No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study

      Dominguez-Valentin, Mev; orcid: 0000-0001-7856-0057; email: Mev.Dominguez.Valentin@rr-research.no; Plazzer, John-Paul; orcid: 0000-0001-5114-4301; email: johnpaul.plazzer@gmail.com; Sampson, Julian R.; email: Sampson@cardiff.ac.uk; Engel, Christoph; orcid: 0000-0002-7247-282X; email: christoph.engel@imise.uni-leipzig.de; Aretz, Stefan; orcid: 0000-0002-5228-1890; email: stefan.aretz@uni-bonn.de; Jenkins, Mark A.; email: m.jenkins@unimelb.edu.au; Sunde, Lone; email: l.sunde@rn.dk; Bernstein, Inge; email: i.bernstein@rn.dk; Capella, Gabriel; orcid: 0000-0002-4669-7320; email: capella.gabriel@gmail.com; Balaguer, Francesc; orcid: 0000-0002-0206-0539; email: fprunes@clinic.cat; et al. (MDPI, 2021-06-28)
      Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
    • ‘No idea of time’: Parents report differences in autistic children’s behaviour relating to time in a mixed-methods study

      Poole, Daniel; orcid: 0000-0002-7399-2499; email: daniel.poole@manchester.ac.uk; Gowen, Emma; orcid: 0000-0003-4788-4280; Poliakoff, Ellen; Jones, Luke A (SAGE Publications, 2021-04-30)
      An emerging body of research suggests that temporal processing may be disrupted in autistic children, although little is known about behaviours relating to time in daily life. In the present study, 113 parents of autistic and 201 parents of neurotypical children (aged 7–12 years) completed the It’s About Time questionnaire and open-ended questions about their child’s behaviour relating to time. The questionnaire scores were lower in the autistic compared with the neurotypical group, suggesting that behaviours are affected. Three key themes were identified using thematic analysis: autistic children had problems with temporal knowledge, learning about concepts relating to time, such as how to use the clock and language around time. There were differences in prospection with autistic children having more difficulties with how they thought about the future and prepared themselves for upcoming events. The final theme, monotropism, described how autistic children viewed their time as precious so they could maximise engagement in their interests. The present study indicates that behaviours relating to time can have a considerable impact on the daily lives of autistic children and their families. Further work exploring the development of temporal cognition in autism would be valuable for targeting effective educational and clinical support. Lay abstract: Many everyday activities require us to organise our behaviours with respect to time. There is some evidence that autistic children have problems with how they perceive and understand time. However, little is currently known about this, or the ways in which behaviours related to time are impacted in daily life. In this study, 113 parents of autistic children and 201 parents of neurotypical children completed a questionnaire and open-ended questions about their child’s behaviour relating to time. Questionnaire scores were lower in the autistic group compared with neurotypicals, which suggests that behaviours relating to time are affected in autistic children. The open-ended responses further confirmed that the autistic children struggled with time and that this impacted on them and their family. Three key themes were identified. Theme 1: autistic children have problems with learning about concepts relating to time such as telling the time from a clock and using words to describe time (hours, minutes, etc.) appropriately. Theme 2: autistic children think about the future differently. Planning and working under time pressure were described as a problem. Theme 3: autistic children have strong interests which take up a lot of their attention and worrying about having sufficient time to pursue these interests causes anxiety. This research indicates that behaviours related to time can have a considerable impact on the lives of autistic children and that targeted support may be required.
    • “No Way Out Except From External Intervention”: First-Hand Accounts of Autistic Inertia

      Buckle, Karen Leneh; email: karenleneh.buckle@manchester.ac.uk; Leadbitter, Kathy; Poliakoff, Ellen; Gowen, Emma (Frontiers Media S.A., 2021-07-13)
      This study, called for by autistic people and led by an autistic researcher, is the first to explore ‘autistic inertia,’ a widespread and often debilitating difficulty acting on their intentions. Previous research has considered initiation only in the context of social interaction or experimental conditions. This study is unique in considering difficulty initiating tasks of any type in real life settings, and by gathering qualitative data directly from autistic people. Four face-to-face and 2 online (text) focus groups were conducted with 32 autistic adults (19 female, 8 male, and 5 other), aged 23–64 who were able to express their internal experiences in words. They articulate in detail the actions they have difficulty with, what makes it easier or harder to act, and the impact on their lives. Thematic analysis of the transcripts found four overarching themes: descriptions of inertia, scaffolding to support action, the influence of wellbeing, and the impact on day-to-day activities. Participants described difficulty starting, stopping and changing activities that was not within their conscious control. While difficulty with planning was common, a subset of participants described a profound impairment in initiating even simple actions more suggestive of a movement disorder. Prompting and compatible activity in the environment promoted action, while mental health difficulties and stress exacerbated difficulties. Inertia had pervasive effects on participants’ day-to-day activities and wellbeing. This overdue research opens the door to many areas of further investigation to better understand autistic inertia and effective support strategies.
    • Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress

      Shea, Sue; email: sue.shea@warwick.ac.uk; Lionis, Christos; orcid: 0000-0002-9324-2839; email: lionis@galinos.med.uoc.gr; Kite, Chris; orcid: 0000-0003-1342-274X; email: c.kite@chester.ac.uk; Atkinson, Lou; orcid: 0000-0003-1613-3791; email: l.atkinson1@aston.ac.uk; Chaggar, Surinderjeet S.; email: surinder.chaggar@nhs.net; Randeva, Harpal S.; email: harpal.randeva@uhcw.nhs.uk; Kyrou, Ioannis; email: ad6702@coventry.ac.uk (MDPI, 2021-11-16)
      Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.
    • Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress.

      Shea, Sue; Lionis, Christos; orcid: 0000-0002-9324-2839; Kite, Chris; orcid: 0000-0003-1342-274X; Atkinson, Lou; orcid: 0000-0003-1613-3791; Chaggar, Surinderjeet S; Randeva, Harpal S; Kyrou, Ioannis (2021-11-16)
      Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.
    • Non-invasive objective tools for quantitative assessment of skin scarring.

      Ud-Din, Sara; email: sara.ud-din@manchester.ac.uk; Bayat, Ardeshir; email: ardeshir.bayat@manchester.ac.uk (2021-05-08)
      Multiple treatment modalities are utilised in the management of skin scarring, however, due to high recurrence rates and unknown resolution rates it can be difficult to assess if treatment is suitable or effective for the individual patient in particular in the case of raised dermal scarring. Therefore, it is necessary to evaluate these treatments and provide accurate scar assessment pre- & post-therapy in order to quantify scar characteristics using objective assessment tools, particularly non-invasive devices. Recent Advances: There have been a number of emerging non-invasive objective quantitative devices which assess specific scar parameters such as pliability, firmness, volume, colour, perfusion and depth. These can include 3-dimensional imaging, optical coherence tomography, in vivo confocal microscopy, full-field laser perfusion imaging and spectrophotometric intracutaneous analysis. Clinical assessment and grading scales are most commonly used to assess scarring, however, there is a need for more objective quantitative measures to monitor their maturation and response to therapy. Currently, there is no consensus as to which objective measuring device is most optimal when assessing skin scarring. There is a need for a predictor tool which allows early implementation of treatment and addresses diagnosis, therapy and prognosis. Future technological advances and further validation of non-invasive objective scar assessment tools is essential. At present there is a greater emphasis on tools to assess the physical scar parameters rather than the physiological characteristics. Therefore, it is essential to develop a tool which measures the metabolic and cellular activity in scars in order to tailor treatment to each individual.
    • Non-Newtonian Droplet Generation in a Cross-Junction Microfluidic Channel

      Fatehifar, Maryam; orcid: 0000-0002-8770-729X; email: maryam.fatehifar@postgrad.manchester.ac.uk; Revell, Alistair; orcid: 0000-0001-7435-1506; email: alistair.revell@manchester.ac.uk; Jabbari, Masoud; orcid: 0000-0003-3615-969X; email: m.jabbari@manchester.ac.uk (MDPI, 2021-06-09)
      A two-dimensional CFD model based on volume-of-fluid (VOF) is introduced to examine droplet generation in a cross-junction microfluidic using an open-source software, OpenFOAM together with an interFoam solver. Non-Newtonian power-law droplets in Newtonian liquid is numerically studied and its effect on droplet size and detachment time in three different regimes, i.e., squeezing, dripping and jetting, are investigated. To understand the droplet formation mechanism, the shear-thinning behaviour was enhanced by increasing the polymer concentrations in the dispersed phase. It is observed that by choosing a shear-dependent fluid, droplet size decreases compared to Newtonian fluids while detachment time increases due to higher apparent viscosity. Moreover, the rheological parameters—n and K in the power-law model—impose a considerable effect on the droplet size and detachment time, especially in the dripping and jetting regimes. Those parameters also have the potential to change the formation regime if the capillary number (Ca) is high enough. This work extends the understanding of non-Newtonian droplet formation in microfluidics to control the droplet characteristics in applications involving shear-thinning polymeric solutions.
    • Non-territorial GPS-tagged golden eagles Aquila chrysaetos at two Scottish wind farms: Avoidance influenced by preferred habitat distribution, wind speed and blade motion status

      editor: Magar, Vanesa; Fielding, Alan H.; Anderson, David; Benn, Stuart; Dennis, Roy; Geary, Matthew; Weston, Ewan; Whitfield, D. Philip; orcid: 0000-0003-4255-7782; email: phil.whitfield@natural-research.org (Public Library of Science, 2021-08-05)
      Wind farms can have two broad potential adverse effects on birds via antagonistic processes: displacement from the vicinity of turbines (avoidance), or death through collision with rotating turbine blades. These effects may not be mutually exclusive. Using detailed data from 99 turbines at two wind farms in central Scotland and thousands of GPS-telemetry data from dispersing golden eagles, we tested three hypotheses. Before-and-after-operation analyses supported the hypothesis of avoidance: displacement was reduced at turbine locations in more preferred habitat and with more preferred habitat nearby. After-operation analyses (i.e. from the period when turbines were operational) showed that at higher wind speeds and in highly preferred habitat eagles were less wary of turbines with motionless blades: rejecting our second hypothesis. Our third hypothesis was supported, since at higher wind speeds eagles flew closer to operational turbines; especially–once more–turbines in more preferred habitat. After operation, eagles effectively abandoned inner turbine locations, and flight line records close to rotor blades were rare. While our study indicated that whole-wind farm functional habitat loss through avoidance was the substantial adverse impact, we make recommendations on future wind farm design to minimise collision risk further. These largely entail developers avoiding outer turbine locations which are in and surrounded by swathes of preferred habitat. Our study illustrates the insights which detailed case studies of large raptors at wind farms can bring and emphasises that the balance between avoidance and collision can have several influences.
    • Non-territorial GPS-tagged golden eagles Aquila chrysaetos at two Scottish wind farms: Avoidance influenced by preferred habitat distribution, wind speed and blade motion status.

      Fielding, Alan H; Anderson, David; Benn, Stuart; Dennis, Roy; Geary, Matthew; Weston, Ewan; Whitfield, D Philip; orcid: 0000-0003-4255-7782 (2021-08-05)
      Wind farms can have two broad potential adverse effects on birds via antagonistic processes: displacement from the vicinity of turbines (avoidance), or death through collision with rotating turbine blades. These effects may not be mutually exclusive. Using detailed data from 99 turbines at two wind farms in central Scotland and thousands of GPS-telemetry data from dispersing golden eagles, we tested three hypotheses. Before-and-after-operation analyses supported the hypothesis of avoidance: displacement was reduced at turbine locations in more preferred habitat and with more preferred habitat nearby. After-operation analyses (i.e. from the period when turbines were operational) showed that at higher wind speeds and in highly preferred habitat eagles were less wary of turbines with motionless blades: rejecting our second hypothesis. Our third hypothesis was supported, since at higher wind speeds eagles flew closer to operational turbines; especially-once more-turbines in more preferred habitat. After operation, eagles effectively abandoned inner turbine locations, and flight line records close to rotor blades were rare. While our study indicated that whole-wind farm functional habitat loss through avoidance was the substantial adverse impact, we make recommendations on future wind farm design to minimise collision risk further. These largely entail developers avoiding outer turbine locations which are in and surrounded by swathes of preferred habitat. Our study illustrates the insights which detailed case studies of large raptors at wind farms can bring and emphasises that the balance between avoidance and collision can have several influences.
    • Norwegian youngsters’ perceptions of physical education: exploring the implications for mental health

      Røset, Linda; orcid: 0000-0003-3377-7636; Green, Ken; orcid: 0000-0003-1692-7065; Thurston, Miranda; orcid: 0000-0001-7779-3836 (Informa UK Limited, 2019-06-24)
    • Not only laboratory to clinic: the translational work of William S. C. Copeman in rheumatology

      Worboys, Michael; orcid: 0000-0001-8583-7931; email: michael.worboys@manchester.ac.uk; Toon, Elizabeth (Springer International Publishing, 2020-08-06)
      Abstract: Since the arrival of Translational Medicine (TM), as both a term and movement in the late 1990s, it has been associated almost exclusively with attempts to accelerate the “translation” of research-laboratory findings to improve efficacy and outcomes in clinical practice (Krueger et al. in Hist Philos Life Sci 41:57, 2019). This framing privileges one source of change in medicine, that from bench-to-bedside. In this article we dig into the history of translation research to identify and discuss three other types of translational work in medicine that can also reshape ideas, practices, institutions, behaviours, or all of these, to produce transformations in clinical effectiveness. These are: (1) making accessible state-of-the-art knowledge and best practice across the medical profession; (2) remodelling and creating institutions to better develop and make available specialist knowledge and practice; and (3) improving public and patient understandings of disease prevention, symptoms and treatments. We do so by examining the work of William S. C. Copeman, a dominant figure in British rheumatology from the 1930 through the late 1960s. Throughout his long career, Copeman blended approaches to “translation” in order to produce transformative change in clinical medicine, making his work an exemplar of our expanded notion of TM.
    • Notch Signalling in Breast Development and Cancer

      Edwards, Abigail; Brennan, Keith; email: keith.brennan@manchester.ac.uk (Frontiers Media S.A., 2021-07-06)
      The Notch signalling pathway is a highly conserved developmental signalling pathway, with vital roles in determining cell fate during embryonic development and tissue homeostasis. Aberrant Notch signalling has been implicated in many disease pathologies, including cancer. In this review, we will outline the mechanism and regulation of the Notch signalling pathway. We will also outline the role Notch signalling plays in normal mammary gland development and how Notch signalling is implicated in breast cancer tumorigenesis and progression. We will cover how Notch signalling controls several different hallmarks of cancer within epithelial cells with sections focussed on its roles in proliferation, apoptosis, invasion, and metastasis. We will provide evidence for Notch signalling in the breast cancer stem cell phenotype, which also has implications for therapy resistance and disease relapse in breast cancer patients. Finally, we will summarise the developments in therapeutic targeting of Notch signalling, and the pros and cons of this approach for the treatment of breast cancer.
    • Notes on the genus Chinattus Logunov, 1999 from India, Pakistan and Nepal (Arachnida: Araneae: Salticidae).

      Logunov, Dmitri V; email: dmitri.v.logunov@manchester.ac.uk (2021-07-29)
      A new speciesChinattus mikhailovi sp. nov. (♂♀, from Pakistan, Peshawar)is diagnosed, described and illustrated. New records of Chinattus validus (Xie, Peng et Kim, 1993) from Nepal, India (Himachal Pradesh) and Vietnam, and C. chichila Logunov, 2003 from Nepal are presented. The collecting localities of all three species are mapped. A brief discussion of the state of knowledge of the genus Chinattus Logunov, 1999 is provided as well.
    • Nothing about us without us: involving patient collaborators for machine learning applications in rheumatology.

      Shoop-Worrall, Stephanie J W; orcid: 0000-0002-9441-5535; email: stephanie.shoop-worrall@manchester.ac.uk; Cresswell, Katherine; Bolger, Imogen; Dillon, Beth; Hyrich, Kimme L; orcid: 0000-0001-8242-9262; Geifman, Nophar; Members of the CLUSTER consortium (2021-07-05)
      Novel machine learning methods open the door to advances in rheumatology through application to complex, high-dimensional data, otherwise difficult to analyse. Results from such efforts could provide better classification of disease, decision support for therapy selection, and automated interpretation of clinical images. Nevertheless, such data-driven approaches could potentially model noise, or miss true clinical phenomena. One proposed solution to ensure clinically meaningful machine learning models is to involve primary stakeholders in their development and interpretation. Including patient and health care professionals' input and priorities, in combination with statistical fit measures, allows for any resulting models to be well fit, meaningful, and fit for practice in the wider rheumatological community. Here we describe outputs from workshops that involved healthcare professionals, and young people from the Your Rheum Young Person's Advisory Group, in the development of complex machine learning models. These were developed to better describe trajectory of early juvenile idiopathic arthritis disease, as part of the CLUSTER consortium. We further provide key instructions for reproducibility of this process.Involving people living with, and managing, a disease investigated using machine learning techniques, is feasible, impactful and empowering for all those involved. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.]
    • Novel methodology to assess the effect of contouring variation on treatment outcome

      Jenkins, Alexander; Mullen, Thomas Soares; Johnson‐Hart, Corinne; Green, Andrew; McWilliam, Alan; Aznar, Marianne; van Herk, Marcel; Vasquez Osorio, Eliana; email: eliana.vasquezosorio@manchester.ac.uk (2021-04-24)
      Purpose: Contouring variation is one of the largest systematic uncertainties in radiotherapy, yet its effect on clinical outcome has never been analyzed quantitatively. We propose a novel, robust methodology to locally quantify target contour variation in a large patient cohort and find where this variation correlates with treatment outcome. We demonstrate its use on biochemical recurrence for prostate cancer patients. Method: We propose to compare each patient’s target contours to a consistent and unbiased reference. This reference was created by auto‐contouring each patient’s target using an externally trained deep learning algorithm. Local contour deviation measured from the reference to the manual contour was projected to a common frame of reference, creating contour deviation maps for each patient. By stacking the contour deviation maps, time to event was modeled pixel‐wise using a multivariate Cox proportional hazards model (CPHM). Hazard ratio (HR) maps for each covariate were created, and regions of significance found using cluster‐based permutation testing on the z‐statistics. This methodology was applied to clinical target volume (CTV) contours, containing only the prostate gland, from 232 intermediate‐ and high‐risk prostate cancer patients. The reference contours were created using ADMIRE® v3.4 (Elekta AB, Sweden). Local contour deviations were computed in a spherical coordinate frame, where differences between reference and clinical contours were projected in a 2D map corresponding to sampling across the coronal and transverse angles every 3°. Time to biochemical recurrence was modeled using the pixel‐wise CPHM analysis accounting for contour deviation, patient age, Gleason score, and treated CTV volume. Results: We successfully applied the proposed methodology to a large patient cohort containing data from 232 patients. In this patient cohort, our analysis highlighted regions where the contour variation was related to biochemical recurrence, producing expected and unexpected results: (a) the interface between prostate–bladder and prostate–seminal vesicle interfaces where increase in the manual contour relative to the reference was related to a reduction of risk of biochemical recurrence by 4–8% per mm and (b) the prostate's right, anterior and posterior regions where an increase in the manual contour relative to the reference contours was related to an increase in risk of biochemical recurrence by 8–24% per mm. Conclusion: We proposed and successfully applied a novel methodology to explore the correlation between contour variation and treatment outcome. We analyzed the effect of contour deviation of the prostate CTV on biochemical recurrence for a cohort of more than 200 prostate cancer patients while taking basic clinical variables into account. Applying this methodology to a larger dataset including additional clinically important covariates and externally validating it can more robustly identify regions where contour variation directly relates to treatment outcome. For example, in the prostate case we use to demonstrate our novel methodology, external validation will help confirm or reject the counter‐intuitive results (larger contours resulting in higher risk). Ultimately, the results of this methodology could inform contouring protocols based on actual patient outcomes.
    • Novel Reviews

      Toivanen, Anna-Leena; email: anna-leena.toivanen@uef.fi; Taylor, Joanna E.; email: joanna.taylor@manchester.ac.uk (Berghahn Books, 2021-03-01)
      Michèle Rakotoson, Elle, au printemps (Saint-Maur: Sépia, 1996), 122 pp.Kathleen Jamie, Surfacing (UK: Sort of Books, 2019), 240 pp., £7.99. Kathleen Jamie (ed.), Antlers of Water: Writing on the Nature and Environment of Scotland (Edinburgh: Canongate Books, 2020), 232pp., £20.