The origin(s) and geodynamic significance of Archaean ultramafic-mafic bodies in the mainland Lewisian Gneiss Complex, North Atlantic Craton

The geodynamic regime(s) that predominated during the Archaean remains controversial, with the plethora of competing models largely informed by felsic lithologies. Ultramafic-mafic rocks displaying distinctive geochemical signatures are formed in a range of Phanerozoic geotectonic environments. These rocks have high melting points, making them potentially useful tools for investigating Archaean geodynamic processes in highly metamorphosed regions. We present field mapping, petrography, traditional bulk-rock geochemistry, and platinum-group element geochemistry for 12 ultramafic-mafic bodies in the Lewisian Gneiss Complex (LGC), which is a highly metamorphosed fragment of the North Atlantic Craton in northwest Scotland. Our data indicate that most of these occurrences are layered intrusions emplaced into the tonalite-trondhjemite-granodiorite (TTG)-dominated crust prior to polyphase metamorphism, representing a significant re-evaluation of the LGC's magmatic evolution. Of the others, two remain ambiguous, but one (Loch an Daimh Mor) has some geochemical affinity with abyssal/orogenic peridotites and may represent a fragment of Archaean mantle, although further investigation is required. The ultramafic-mafic bodies in the LGC thus represent more than one type of event/process. Compared with the TTG host rocks, these lithologies may preserve evidence of protolith origin(s), with potential to illuminate tectonic setting(s) and geodynamic regimes of the early Earth

Now the wars are over: The past, present and future of Scottish battlefields

Battlefield archaeology has provided a new way of appreciating historic battlefields. This paper provides a summary of the long history of warfare and conflict in Scotland which has given rise to a large number of battlefield sites. Recent moves to highlight the archaeological importance of these sites, in the form of Historic Scotland’s Battlefields Inventory are discussed, along with some of the problems associated with the preservation and management of these important cultural sites

Effects of the COVID-19 lockdown on orthopaedic trauma:a multicentre study across Scotland

Aims: The UK government declared a national lockdown on 23 March 2020 to reduce transmission of COVID-19. This study aims to identify the effect of lockdown on the rates, types, mechanisms, and mortality of musculoskeletal trauma across Scotland.Methods: Data for all musculoskeletal trauma requiring operative treatment were collected prospectively from five key orthopaedic units across Scotland during lockdown (23 March 2020 to 28 May 2020). This was compared with data for the same timeframe in 2019 and 2018. Data collected included all cases requiring surgery, injury type, mechanism of injury, and inpatient mortality.Results: A total of 1,315 patients received operative treatment from 23 March 2020 to 28 May 2020 compared with 1,791 in 2019 and 1,719 in 2018. The numbers of all injury types decreased, but the relative frequency of hip fractures increased (36.3% in 2020 vs 30.2% in 2019, p &lt; 0.0001 and 30.7% in 2018, p &lt; 0.0001). Significant increases were seen in the proportion of DIY-related injuries (3.1% in 2020 vs 1.7% in 2019, p = 0.012 and 1.6% in 2018, p &lt; 0.005) and injuries caused by falls (65.6% in 2020 vs 62.6% in 2019, p = 0.082 and 61.9% in 2018, p = 0.047). Significant decreases were seen in the proportion of road traffic collisions (2.6% in 2020 vs 5.4% in 2019, p &lt; 0.0001 and 4.2% in 2018, p = 0.016), occupational injuries (1.8% in 2020 vs 3.0% in 2019, p = 0.025 and 2.3% in 2018, p = 0.012) and infections (6.8% in 2020 vs 7.8% in 2019, p = 0.268 and 10.3% in 2018, p &lt; 0.012). Cycling injuries increased (78 in 2020 vs 64 in 2019 vs 42 in 2018). A significant increase in the proportion of self-harm injuries was seen (1.7% in 2020 vs 1.1% in 2019, p = 0.185 and 0.5% in 2018, p &lt; 0.0001). Mortality of trauma patients was significantly higher in 2020 (5.0%) than in 2019 (2.8%, p = 0.002) and 2018 (1.8%, p &lt; 0.0001).Conclusion: The UK COVID-19 lockdown has resulted in a marked reduction in musculoskeletal trauma patients undergoing surgery in Scotland. There have been significant changes in types and mechanisms of injury and, concerningly, mortality of trauma patients has risen significantly.</p

Re-evaluating ambiguous age relationships in Archean cratons: Implications for the origin of ultramafic-mafic complexes in the Lewisian Gneiss Complex

Archean ultramafic-mafic complexes have been the focus of important and often contentious geological and geodynamic interpretations. However, their age relative to the other components of Archean cratons are often poorly-constrained, introducing significant ambiguity when interpreting their origin and geodynamic significance. The Lewisian Gneiss Complex (LGC) of the northwest Scottish mainland – a high-grade, tonalite-trondhjemite-granodiorite (TTG) terrane that forms part of the North Atlantic Craton (NAC) – contains a number of ultramafic-mafic complexes whose origin and geodynamic significance have remained enigmatic since they were first described. Previous studies have interpreted these complexes as representing a wide-range of geological environments, from oceanic crust, to the sagducted remnants of Archean greenstone belts. These interpretations, which are often critically dependent upon the ages of the complexes relative to the surrounding rocks, have disparate implications for Archean geodynamic regimes (in the NAC and globally). Most previous authors have inferred that the ultramafic-mafic complexes of the LGC pre-date the TTG magmas. This fundamental age relationship is re-evaluated in this investigation through re-mapping of the Geodh’ nan Sgadan Complex (where tonalitic gneiss reportedly cross-cuts mafic rocks) and new mapping of the 7 km2 Ben Strome Complex (the largest ultramafic-mafic complex in the LGC), alongside detailed petrography and spinel mineral chemistry. This new study reveals that, despite their close proximity in the LGC (12 km), the Ben Strome and Geodh’ nan Sgadan Complexes are petrogenetically unrelated, indicating that the LGC (and thus NAC) records multiple temporally and/or petrogenetically distinct phases of ultramafic-mafic Archean magmatism that has been masked by subsequent high-grade metamorphism. Moreover, field observations and spinel mineral chemistry demonstrate that the Ben Strome Complex represents a layered intrusion that was emplaced into a TTG-dominated crust. Further to representing a significant re-evaluation of the LGC’s magmatic evolution, these findings have important implications for the methodologies utilised in deciphering the origin of Archean ultramafic-mafic complexes globally, where material suitable for dating is often unavailable and field relationships are commonly ambiguous

Novel self-amplificatory loop between T cells and tenocytes as a driver of chronicity in tendon disease

Objectives: Increasing evidence suggests that inflammatory mechanisms play a key role in chronic tendon disease. After observing T cell signatures in human tendinopathy, we explored the interaction between T cells and tendon stromal cells or tenocytes to define their functional contribution to tissue remodelling and inflammation amplification and hence disease perpetuation. Methods: T cells were quantified and characterised in healthy and tendinopathic tissues by flow cytometry (FACS), imaging mass cytometry (IMC) and single cell RNA-seq. Tenocyte activation induced by conditioned media from primary damaged tendon or interleukin-1β was evaluated by qPCR. The role of tenocytes in regulating T cell migration was interrogated in a standard transwell membrane system. T cell activation (cell surface markers by FACS and cytokine release by ELISA) and changes in gene expression in tenocytes (qPCR) were assessed in cocultures of T cells and explanted tenocytes. Results: Significant quantitative differences were observed in healthy compared with tendinopathic tissues. IMC showed T cells in close proximity to tenocytes, suggesting tenocyte–T cell interactions. On activation, tenocytes upregulated inflammatory cytokines, chemokines and adhesion molecules implicated in T cell recruitment and activation. Conditioned media from activated tenocytes induced T cell migration and coculture of tenocytes with T cells resulted in reciprocal activation of T cells. In turn, these activated T cells upregulated production of inflammatory mediators in tenocytes, while increasing the pathogenic collagen 3/collagen 1 ratio. Conclusions: Interaction between T cells and tenocytes induces the expression of inflammatory cytokines/chemokines in tenocytes, alters collagen composition favouring collagen 3 and self-amplifies T cell activation via an auto-regulatory feedback loop. Selectively targeting this adaptive/stromal interface may provide novel translational strategies in the management of human tendon disorders

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

Translational targeting of inflammation and fibrosis in frozen shoulder: Molecular dissection of the T cell/IL-17A axis

Frozen shoulder is a common fibroproliferative disease characterized by the insidious onset of pain and restricted range of shoulder movement with a significant socioeconomic impact. The pathophysiological mechanisms responsible for chronic inflammation and matrix remodeling in this prevalent fibrotic disorder remain unclear; however, increasing evidence implicates dysregulated immunobiology. IL-17A is a key cytokine associated with inflammation and tissue remodeling in numerous musculoskeletal diseases, and thus, we sought to determine the role of IL-17A in the immunopathogenesis of frozen shoulder. We demonstrate an immune cell landscape that switches from a predominantly macrophage population in nondiseased tissue to a T cell-rich environment in disease. Furthermore, we observed a subpopulation of IL-17A-producing T cells capable of inducing profibrotic and inflammatory responses in diseased fibroblasts through enhanced expression of the signaling receptor IL-17RA, rendering diseased cells more sensitive to IL-17A. We further established that the effects of IL-17A on diseased fibroblasts was TRAF-6/NF-κB dependent and could be inhibited by treatment with an IKKβ inhibitor or anti-IL-17A antibody. Accordingly, targeting of the IL-17A pathway may provide future therapeutic approaches to the management of this common, debilitating disease. [Abstract copyright: Copyright © 2021 the Author(s). Published by PNAS.

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches