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Background/Aims Immunosuppression in Takayasu arteritis (TA) reduces the risk of arterial disease progression. However, long-term use of glucocorticoids (GC) and other agents carries risk, particularly as patients age. GC tapering practice can vary and there are no guidelines on the safety of treatment cessation due to a lack of data. This study describes the cessation of treatment in a large single-centre cohort and evaluates the baseline, clinical and treatment parameters associated with successful treatment stop. Methods The Imperial College Takayasu Arteritis Cohort (UK) was reviewed retrospectively; 158 patients, median follow-up 8.4 [5-13.6] years. Patients with data available within 1 year of audit (31/03/2021) were analysed. Treatment was defined as > 6 months of GC, csDMARD or biologic medication and cessation as stopping treatment for >1 year. Cessation safety was assessed by serial angiography (whole aorta MRI or CT) and NIH disease activity scoring. Baseline demographic, clinical and treatment parameters as well as initial treatment responses were compared for cessation and non-cessation cases. Data are median [IQR], comparisons are non-parametric for continuous variables. Results Of 129 (82%) cases requiring treatment, 107 (83%) remained in care. 29 (27.1%) cases of cessation were identified, time off-treatment was 3.6 [2.5-8.2] years. For 25 (86%) cessation cases, treatment withdrawal was due to sustained quiescence. Infection, non-adherence and tolerance accelerated cessation in 4 cases. Long-term inactivity was confirmed by disease activity scoring in all cases and by angiography where available (23 cases). No instances of treatment restart were observed. Baseline demographic and disease severity parameters were similar in cessation and non-cessation patients (Table). Cessation cases had lower GC doses after 2 years of treatment and a trend towards lower disease activity, suggesting better responses. Relatedly, biologic administration (reserved for refractory disease) was markedly lower in the cessation group. Finally, cessation cases had earlier treatment start years, were older at audit and had an increased proportion of Numano Type V classification. Conclusion In TA, complete treatment cessation is feasible and safe in a proportion of cases. Initial treatment response, treatment duration and Numano type V arterial involvement are potential predictors of successful treatment cessation and may aid future stratification strategies after validation. Disclosure R.T. Maughan: None. A. Porter: None. C. Dahanayake: None. C. Ianonne: None. R. Alapat: None. C. Pericleous: None. T.A. Youngstein: None. J. Mason: None.

Background/Aims At diagnosis, a proportion of Takayasu’s arteritis (TAK) cases present with imaging evidence consistent with TAK without evidence of active arteritis or systemic disease. Inactive TAK is considered the end-point of a triphasic disease process characterised by a “burnt-out” non-inflammatory fibrotic state. Current EULAR/ACR guidelines recommend immunosuppressive treatment and routine imaging for active TAK but data guiding the management of inactive disease are scarce. The purpose of this case series was to examine baseline characteristics of patients presenting with inactive TAK and investigate disease progression. Methods We performed a retrospective review of the Imperial College Takayasu Arteritis Cohort. TAK diagnosis was based on imaging evidence in combination with clinical history. Disease was determined inactive by activity scoring indices (ITAS2010 + NIH) together with inflammatory markers. MR Angiogram (28/30 cases) and CT Angiogram (2/30) were utilised as imaging modalities to determine vascular involvement. Disease distribution was characterised using the Numano Classification (Table 1). Results 19% (30/158) of patients presented with “inactive disease” at diagnosis. Inactive cases had a median age of diagnosis of 37.8 years, compared to 33.8 in patients with active disease. 48% of inactive cases experienced >2 year delay in reaching diagnosis. Inactive cases did not display significantly elevated inflammatory markers (CRP 3.86, ESR 27.0) at baseline visit and demonstrated arterial lesions on angiography consistent with standard TA definitions in terms of anatomical distribution and characteristics. Inactive patients were followed up with interval MR imaging, allowing us to chart natural disease course without treatment. Of 30 total cases, only five patients developed progression of vascular lesions. Three patients displayed marginal imaging progression without active symptoms together with normal inflammatory markers; these patients did not receive immunosuppression and serial interval imaging demonstrated stable disease, suggesting a non-inflammatory aetiology. Two patients developed progression attributed to active disease, necessitating treatment with immunosuppression. Conclusion A significant proportion of patients have inactive disease at TAK diagnosis. This presents a challenge to the treating clinician and further uncertainty for patients. This case study provides evidence that cases of burnt-out TAK can be managed safely without immunosuppressive treatment using routine imaging surveillance and serum biomarkers. Disclosure S. Hanlon: None. J. Nouza: None. M. Colquhoun: None. J. Satara: None. A. Porter: None. R. Maughan: None. T. Youngstein: None. J. Mason: None.

Background/Aims The large vessel vasculitis Takayasu arteritis (TA) is initially treated with high dose glucocorticoids (GC) (40-60mg/day), typically with a csDMARD to induce remission. Subsequently, GC doses are tapered to reduce adverse effects. Although current EULAR guidelines tentatively recommend a target GC dose of Methods A retrospective analysis of the Imperial College Takayasu Arteritis Cohort (UK) was undertaken; 158 patients with median follow-up 8.4 [5-13.6] yrs. Patients with sufficient data and typical treatment initiation pattern were analysed, commencing either GC monotherapy or GC + csDMARD and no baseline immunosuppression. Primary outcome: GC Results Of 129 TA cases requiring treatment, 80 (62%) satisfied analysis criteria. Overall, 46 (57.5%) and 59 (73.7%) patients met the primary outcome at years one and two respectively. Of these, 43 (93.5%) and 46 (78%) did so without treatment intensification. Taper success was consistent over time, with 43 (94%) year one taper success cases maintaining status at year two. In most cases (90.5%), year two taper failure was due to inadequate treatment response as confirmed by disease activity scoring (Table). Baseline parameters were similar between groups, except ESR which was significantly lower in the taper success group. As expected, initial treatment with GC monotherapy tended to be lower in the taper success group. At year five, GC doses remained higher and biologic usage was greater in taper failure cases suggesting a more refractory disease course (Table). Conclusion The EULAR GC taper target was achieved in 57.5% of patients, increasing to 73.7% by two years. Clinical implementation of this target is practical and will aid in the reduction of cumulative GC exposure and identification of patients requiring treatment intensification. Disclosure R. Alapat: None. A. Porter: None. C. Pericleous: None. T.A. Youngstein: None. R. Maughan: None. J.C. Mason: None.

Introduction Disrupted sleep has been linked to suicidal thought and behavior. Less is known regarding underlying mechanisms of this relationship. A more nuanced understanding of the link between sleep and suicide may help inform treatment decisions and the development of prevention and intervention strategies. We examine prior day sleepiness as a moderator to the relationship between passive and active suicidal ideation (SI). Methods Young adults (mean age=21.04; SD=2.22) endorsing SI (n=59) at least twice in the past two weeks were enrolled in a trial examining potential iatrogenic effects of the ecological momentary assessment (EMA) of SI. A baseline battery collected data on past suicidal thought and behavior, demographics, and psychological distress. EMA surveys were administered randomly five times per day over four weeks and assessed sleepiness and current emotional state including occurrence and severity of SI and passive/active ideation. Results Altogether, 835 daily average EMA entries were utilized in the present analysis. A significant relationship (p Conclusion This study examined the impact of daily sleepiness on relationships among passive and active SI among young adults endorsing suicidal thought. Findings indicate that the relation between daily passive and active SI severity grows stronger the sleepier one is relative to their average level of sleepiness. Future studies should incorporate objective measures of sleep to further explore these findings and clinical implications. Support (if any) This study was funded by the American Psychological Foundation. This work was also supported, in part, by the VA Center of Excellence for Suicide Prevention. Authors’ views do not necessarily represent those of the Department of Veterans Affairs or the United States Government.

Background/Aims Deficiency of adenosine deaminase 2 (DADA2) leads to a broad phenotype; some patients develope vasculitis and strokes, and others have predominantly haematological manifestations. Small, medium and large vessel vasculitis has been described. In contrast, plasma ADA2 activity is elevated in inflammatory conditions including systemic lupus erythematosus and systemic juvenile idiopathic arthritis with macrophage activation syndrome. The role of ADA2 and how its deficiency associates with the vasculitides is not well understood. Using a well-characterised large vessel vasculitis cohort, we sought to establish the potential role of ADA2 activity. Methods ADA2 activity was measured in adults with Takayasu arteritis (TA), large vessel giant cell arteritis (LV-GCA), intracranial vasculitis (IV) and healthy control (HC) subjects using a coupled spectrophotometric assay. Plasma from 11 patients with genotyped DADA2 and 10 patients heterozygous for pathogenic variants in ADA2 were used to define thresholds for deficiency and carrier status respectively (DADA2 activity 0 - 0.90 U/L, ADA2 carrier activity 2.02 - 10.62 U/L). Activity levels above the upper limit of normal (ULN) were defined as > 99th percentile of the HC activity (30.3U/L). To assess potential associations with TA disease status, ADA2 was measured prospectively in matched active and remission samples. TA disease activity was determined as active, grumbling or stable using clinical and radiological features, physician impression, CRP, ESR and Indian Takayasu clinical Activity Score (ITAS). Results No patients had deficient ADA2 activity while 7 subjects had activity within the carrier range (1 HC [1.9%], 5 TA [3.7%], 1 LV-GCA [2.3%]). Compared to HC levels (17.43 [14.11 - 20.78] U/L), activity in the TA group was significantly increased (TA 19.68U/L, p = 0.0061), while LV-GCA and IV were not significantly different. In 20 cases, activity exceeded the ULN; 16 TA (11.9%, p = 0.044; 4 active, 2 grumbling, 10 stable) and 4 LV-GCA (9.1%, ns). In TA, there was a positive correlation between ADA2 activity and ESR (Spearman R = 0.2863, p = 0.0009) but not with CRP or ITAS score. Subgroup analysis revealed ADA2 activity was most prominently elevated in the stable group relative to HCs (TA stable 20.54 U/L [8.08 - 48.66], median +17.8%, p = 0.0006), but not with active or grumbling disease. Consistent with this, prospective analysis demonstrated a significant increase in ADA2 activity in remission vs active disease (p = 0.024), with activity increasing in 18 (62%) patients achieving remission. Conclusion There were no cases of ADA2 deficiency in this cohort. Consistent with other inflammatory conditions, ADA2 activity was elevated in TA compared to HC subjects. Surprisingly, increased ADA2 activity was linked to stable TA in both cross-sectional and prospective analyses. This may suggest a potential role of ADA2 enzyme activity in vascular repair and regrowth - possibly tying in with known elevated levels of ADA2 activity in growing children. Disclosure A. Porter: None. R. Maughan: None. C. Pericleous: None. A. Kiprianos: None. H. Jee: None. P. Lee: None. T. Youngstein: None. J. Mason: None.

Aims To assess the feasibility of conducting a large-scale quality-control exercise on the echocardiographic grading of mitral regurgitation (MR). Methods and results One hundred and fifty-two practising cardiologist and sonographer echocardiographers attended a dedicated session within a national meeting and were asked to review echocardiographic images of five case studies and evaluate the severity of MR using a six-point scale. The group's overall evaluation was analysed together with the variation in grading of severity. The proportion of gradings of MR more than one grade either side of the mode was

Advancements in automated high-performance thin-layer chromatography (HPTLC) have made it feasible to assess its use for the quantitative analysis of marker compounds in botanical preparations. We report here the findings of method comparisons for the terpenelactones and flavonol aglycones by column high-performance liquid chromatography (HPLC) with evaporative light scattering and UV detection, and HPTLC with a scanning densitometer. For the HPTLC assay of terpenelactones, total bilobalide, ginkgolide A, and ginkgolide B consistently achieved

We report here a liquid chromatography (LC) method with inline ultraviolet/evaporative light scattering (UV/ELS) detection for the simultaneous quantification of the terpenelactones and flavonol aglycones in a single sample of hydrolyzed Ginkgo biloba extract (GBE). The sample is hydrolyzed by a rapid and convenient oven heating method for 1 h at 90°C with 10% hydrochloric acid. The 1 h hydrolysis was found to be equivalent to the 2.25 h reflux treatment for dry powder extract, where total flavonol glycosides were 28.4 and 28.1%, respectively. Acceptable precision was achieved for total terpenelactones [relative standard deviation (RSD) = 4.8%] by ELS detection, and total flavonol aglycones (RSD = 2.3%) by UV detection. The analytical range was 1.5 to 7.3% (w/w) for the individual terpenelactones (ELS) and 2.5 to 15.0% (w/w) for the individual glycosides (UV) calculated from the aglycones quercetin, kaempferol, and isorhamnetin. This improved method allows for the first time high throughput sample preparation coupled with the quantification of the predominant compounds generally used for quality control of GBE in a single assay.

Preparations from comfrey (Symphytum officinale and S. x uplandicum) root and leaf contain varying levels of the hepatotoxic pyrrolizidine alkaloids (PAs). Reference compounds for comfrey are not commercially available, and there is currently no rapid extraction or analytical method capable of determining low levels in raw materials or as adulterants in commercially available extracts. A solid-phase extraction (SPE) method was developed using an Ergosil cleanup column that specifically binds the PAs. With this method, powdered comfrey root was extracted by sonication and shaking with basic chloroform. The extract was applied to the cleanup column under vacuum, washed with 2 mL acetone–chloroform (8 + 2, v/v) followed by 2 mL petroleum ether to remove excess chloroform. The column was dried under vacuum, and the PAs were eluted with 2 successive 1 mL aliquots methanol. Percent recoveries of the PAs following Ergosil SPE had an overall average of 96.8%, with RSD of 3.8% over a range of 1.0 to 25.0 g extracted in 100 mL. Average precision of the method (n = 3 over 4 extraction concentrations) gave an overall RSD of 6.0% for the 5 alkaloids, with a range of 0.8% (5 g in 100 mL) to 11.2% (25 g in 100 mL). Recovery optimization testing showed that 1.0 g comfrey root extracted in 100 mL yielded the greatest recovery (% dry weight) of the PAs, with an extraction efficiency and accuracy of 94.2%, and RSD of 1.7% (n = 9). The unique properties of the Ergosil cleanup column provide rapid sample cleanup, volume reduction, and concentration of PAs from comfrey extracts, and allow the eluant to be analyzed directly by traditional chromatographic methods.

Children who have suffered extensive unilateral brain injury early in life may show a remarkable degree of residual sensorimotor function. It is generally believed that this reflects the high capacity of the immature brain for cerebral reorganization. In this study, we investigated 17 patients who had undergone hemispherectomy for relief from seizures; eight of the patients had congenital brain damage and nine had sustained their initial insult at the age of 1 year or older. Sensorimotor functions of the hand were investigated using functional MRI (fMRI) during a passive movement task, somatosensory evoked potentials (SEPs) arising from electrical and vibration stimulation, and behavioural tests including grip strength, double simultaneous stimulation and joint position sense. On fMRI, two of the eight patients studied with this technique (one with congenital damage and one with damage acquired at the age of 3 years) showed activation in the sensorimotor cortex of the remaining hemisphere with passive movement of the hemiplegic hand. The location of the ipsilateral brain activation was similar to that found on movement of the normal contralateral hand, although the latter was greater in spatial extent. In one of these patients, a greater role was demonstrated for the ipsilateral secondary sensorimotor area (compared with the ipsilateral primary sensorimotor area) for movement of the hemiplegic hand than for movement of the normal hand. Median nerve stimulation of the hemiplegic hand showed reproducible early-latency ipsilateral SEP components in the remaining sensorimotor cortex in 10 of the 17 patients (five with congenital and five with acquired disease). Five of the patients who demonstrated ipsilateral electrical SEPs also showed ipsilateral vibration SEPs (two with congenital and three with acquired disease). The behavioural tests revealed residual sensorimotor function in 14 of the patients; however, not all of the patients who exhibited ipsilateral SEP or fMRI responses had residual sensorimotor function in the hemiplegic hand. Ipsilateral sensorimotor responses were demonstrated both in patients with congenital disease and those with acquired disease, suggesting that factors additional to aetiology and age at injury may influence the degree of residual sensorimotor function and cerebral reorganization.

Historians' perceptions of the significance of the South African War (1899-1902) have changed considerably over a century. For a long time, its military magnitude, its importance in shaping a global capitalist system, and the stimulus it provided to theoretical understanding of imperialism, were felt to give the war an important role in the making of the modern world. Recent perspectives, both fed by and represented in the centenary commemorations, have replaced these grand sweeps with attention to the many and detailed South African wars experienced at first hand by different individuals and segments of Britain's and South Africa's populations. There is a case for suggesting that the place of the war in Britain's broader domestic and imperial history is now and perhaps rightly-neglected, in part as a consequence of the fragmentation encouraged by historiographical specialization and also because an exaggerated importance was attributed to it for so long. THE MILLENNIUM LECTURES organized by the Historical Association aim to mark significant events of the past which also have an anniversary connection to the year in which the lecture is given. In accepting the Association's invitation, it was difficult for an imperial historian with my record to escape the subject of the South African, or Boer, War. That conflict started on 1 1 October 1899 and preoccupied Britain for some two and a half years, until a peace treaty was agreed at Vereeniging on the Vaal River on 23 May 1902. Still more to the point is that today coincides directly with the centenary of what was at the time rapidly christened 'Black Week'. On 10 December 1899 at Stormberg railway junction in the eastern Cape Colony, on the following day at Magersfontein Hill in the west of the Orange Free State, and on 15 December at Colenso on the Tugela River in Natal, imperial forces were defeated with heavy losses. In these major engagements on each of the three principal fronts of the war, Lt-General Sir William Gatacre, Lord Methuen, and the overall commander General Sir Redvers Buller not only lost almost 10 percent of their troops to Boer forces perhaps two-thirds their size, but damaged their own military reputations virtually beyond repair. Lords Roberts and Kitchener were Andrew Porter is Rhodes Professor of Imperial History at King's College, London. This article is the text of a public lecture given at the Society of Antiquaries, Burlington House, London on 10 December 1999.

We recently reported on three young patients with severe impairments of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic-ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic-ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic-ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus. On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory impairments primarily to hypoxic-ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia-ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic-ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood.

Summary Slow P has been an acceptable form of oral phosphate therapy in a series of patients with a variety of bone disease. Therapeutic responses have been achieved in a number of patients without side effects together with minor elevation of the serum and urinary phosphate in the majority of patients. Some patients have continued with such supplements for several months which encourages an extended trial under more stringent conditions.

From 1816 various attempts were made by London impresarios to engage Rossini. The first to succeed was negotiated in I823just after 'Semiramide' had crowned Rossini's Italian career, at the time when Stendhal could write: "The glory of this man knows no bounds but those of civilizati6n itself, and he is not yet 23". The engagement, made by Giambattista Benelli, was a joint one for Rossini and his wife Isabella Colbran. In the 1824 season she was to sing at the King's Theatre, and he was to compose for it "a two-act opera on a libretto entitled 'La figlia dell'aria'. The agreed price for this score was 6000 francs, payable in three thirds: the first on the composer's arrival in London, the second on the delivery of the first act, and the rest on the delivery of the second". Thus Azevedo'; Radiciotti2 does not mention the title of the opera, and gives the figure as ?240, "an extraordinary sum for the time". The agreement could not have been made before May 1823. In that month Benelli, in mid-season, took over the King's Theatre from John Ebers. For ?Io,ooo he bought the lease (which had two years more to run), scenery, wardrobe and properties; he undertook the financial and contractual responsibilities of the 1823 season, while Ebers continued as manager; from 1824 he was to be in sole charge. Benelli's solicitors, Messrs. Yallop and Chippendale (of whom we shall hear more) "gave a bond for the performance of the covenants in the lease"3.

BENJAMIN BRITTEN'S sixth opera, 'Billy Budd', with libretto by E. M. Forster and Eric Crozier, was presented for the first time at the Royal Opera House, Covent Garden, on December ISt 1951. The subject of the opera derives from Melville's short novel, 'Billy Budd, Foretopman'. Its action is set late in the eighteenth century, soon after the mutinies of Spithead and the Nore. Billy Budd, a handsome sailor, filled with " natural goodness " and beloved of his shipmates, is impressed on to H.M.S. Indomitable, a man-of-war. The warship's master-at-arms, John Claggart, a man filled with ( natural depravity ", conceives an envy of him, and denounces him to Vere, the captain, as an inciter of mutiny. Billy, a stammerer and unable to defend his innocence, strikes Claggart, who falls dead. Vere decides that he shall be executed, and he is hanged. The anecdote is told unrealistically, in poetic phrases which give it as little actuality as a fairy tale. No mind-states are explicitly defined. Indeed the evocative power of the book lies largely in its avoidance of definition. But plainly it is a study of envy, the most active of the passions, which must work ceaselessly to destroy its object. " Since its lodgment is in the heart not the brain, no degree of intellect supplies a guarantee against it. But Claggart's was no vulgar form of the passion. Nor, as directed towards Billy Budd, did it partake of that streak of apprehensive jealousy which marred Saul's visage perturbedly brooding on the comely young David. Claggart's envy struck deeper. If askance he eyed the good looks, cheery health and frank enjoyment of young life in Billy Budd, it is because these went along with a nature that, as Claggart magnetically felt, had in its simplicity never willed malice or experienced the reactionary bite of that serpent." There is, of course, another element in Claggart's hatred; he looks at Billy with " a touch of soft yearning, as if he could even have loved Billy but for fate and ban ". But this undertone runs through the description of what all the characters think of the Iandsome Sailor, and seems to be no more than a projection of the love Melville felt for his hero.