Renovators of old buildings sometimes discover concealed inscriptions made by past tradesmen. They are a means of communicating with fellow workers and posterity and passing on the traditional ...culture of the building trade. This article investigates a collection of graffiti created by early nineteenth-century plumbers. It explores how and why these marks were made -in celebration of tradesmen's skills - and deduces their meanings, with particular relevance to the noxious and dangerous trade of plumbing. It analyses how these values are reflected in other surviving English plumbers' material culture and outlines the wider use of working-class graffiti.
The Great War Mansfield, Nick; Horner, Craig
2014, 2014-06-19
eBook
The First World War was one of the prime motors of social change in modern British history. Culture and technology at all levels were transformed. The growing impact of the state, the introduction of ...modern democracy and change in political allegiance affected most aspects of the lives of UK citizens. Whilst most of the current centenary interest focuses on military aspects of the conflict, this volume considers how these fundamental changes varied from locality to locality within Britains.
ABSTRACT
Background
Current guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organ-threatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated ...vasculitis (AAV), although few studies have examined the efficacy and safety of these agents in combination.
Methods
We conducted a single-centre cohort study of 66 patients treated with a combination of oral corticosteroids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of azathioprine and tapered steroid for the treatment of biopsy-proven renal involvement in AAV. Patients were followed for a median of 56 months. Case–control analysis with 198 propensity-matched cases from European Vasculitis Study Group (EUVAS) trials compared long-term differences in relapse-free, renal and patient survival.
Results
At entry, the median Birmingham Vasculitis Activity Score (BVAS) was 19 and estimated glomerular filtration rate was 25 mL/min. Cumulative doses of rituximab, cyclophosphamide and corticosteroids were 2, 3 and 4.2 g, respectively, at 6 months. A total of 94% of patients achieved disease remission by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%, respectively, at 5 years. A total of 84% achieved ANCA-negative status and 57% remained B cell deplete at 2 years, which was associated with low rates of major relapse (15% at 5 years). The serious infection rate during long-term follow-up was 1.24 per 10 patient-years. Treatment with this regimen was associated with a reduced risk of death {hazard ratio HR 0.29 95% confidence interval (CI) 0.125–0.675, P = 0.004}, progression to end-stage renal disease (ESRD) HR 0.20 (95% CI 0.06–0.65), P = 0.007 and relapse HR 0.49 (95% CI 0.25–0.97), P = 0.04 compared with propensity-matched patients enrolled in EUVAS trials.
Conclusions
This regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.
Sepsis and septic shock continue to contribute to our workload and stimulate our research activities although many fundamental questions remain. Studies reported on here focus on inotrope use and a ...novel way of predicting inotrope response. Continuing this theme more fundamental work is reported examining the mitochondrial respiratory chain and the effects of sepsis coupled with interesting work on lactic acidosis. Troponin raises its head again and we are still left quizzing over its value in the ICU. Finally we discuss a paper on the outcome of the obese patient on a general ICU. Like sepsis a continuing challenge.
Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end-stage kidney disease and associated with poor outcomes after kidney transplantation from early disease recurrence. Prophylactic ...eculizumab treatment at the time of transplantation is used in selected patients with aHUS. We report a retrospective case note review describing transplant outcomes in patients with aHUS transplanted between 1978 and 2017, including those patients treated with eculizumab.
The National Renal Complement Therapeutics Centre database identified 118 kidney transplants in 86 recipients who had a confirmed diagnosis of aHUS. Thirty-eight kidney transplants were performed in 38 recipients who received prophylactic eculizumab. The cohort not treated with eculizumab comprised 80 transplants in 60 recipients and was refined to produce a comparable cohort of 33 transplants in 32 medium and high-risk recipients implanted since 2002. Complement pathway genetic screening was performed. Graft survival was censored for graft function at last follow-up or patient death. Graft survival without eculizumab treatment is described by complement defect status and by Kidney Disease: Improving Global Outcomes risk stratification.
Prophylactic eculizumab treatment improved renal allograft survival ( P = 0.006) in medium and high-risk recipients with 1-y survival of 97% versus 64% in untreated patients. Our data supports the risk stratification advised by Kidney Disease: Improving Global Outcomes.
Prophylactic eculizumab treatment dramatically improves graft survival making transplantation a viable therapeutic option in aHUS.
Background. The Th17 subset has been implicated in the pathogenesis of a number of autoimmune diseases. However, little is known about its role in anti-neutrophil cytoplasm antibody (ANCA)-associated ...vasculitis (AAV). We measured serum levels of IL-17A and associated upstream cytokines and the frequency of IL-17-producing autoantigen-specific T cells in patients with AAV. Methods. ELISA on sera from acute (n = 28) and convalescent (n = 65) patients with AAV from Hammersmith Hospital was performed for IL-17A and the associated upstream cytokines IL-23, IL-6 and IL-1β, as well as the Th1 cytokine IFN-γ. ELISPOT was performed to measure autoantigen-specific recall T cell responses in convalescent patients and the frequency of IL-17- and IFN-γ-producing cells. Results. Serum IL-17A and IL-23 levels were significantly elevated in acute AAV patients compared to healthy controls (P < 0.01 and P < 0.001, respectively), but importantly, remained elevated in a proportion of convalescent patients. By contrast, no significant differences in IFN-γ levels were detected between patient groups and controls. Patients with elevated levels of IL-23 compared to those with low IL-23 had more active disease as measured by Birmingham Vasculitis Activity Score (P < 0.05) and had higher ANCA titres (P < 0.05). Critically, immunosuppressive therapy did not always effectively suppress IL-23 or IL-17 production. Additionally, autoantigen-specific IL-17-producing, but not IFN-γ-producing, cells were significantly elevated in patients during disease convalescence compared to healthy controls. Conclusions. These data implicate the Th17 axis and specifically IL-23 as mediators of more severe disease in AAV. Their persistence despite conventional treatment may contribute to high relapse rates.
Rituximab (RTX) has been shown to be effective as an induction agent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but studies have been limited by short-term follow-up. ...We decided to investigate the long-term efficacy and safety of an RTX-based cyclophosphamide (CYP)-sparing regimen (CycLowVas) for renal AAV.
Consecutive patients with renal AAV presenting de novo or with a major relapse, except those with serum creatinine >500 μmol/L, previous treatment with RTX and pulmonary haemorrhage or cerebral vasculitis, were treated with two pulses of RTX 2 weeks apart and six fortnightly doses of CYP, as well as a reducing protocol of daily oral steroids. Maintenance was with low-dose steroids and azathioprine.
Twenty-three patients were treated. Median follow-up was 39 months, with 17 patients reaching >2 years of follow-up. All patients achieved clinical remission within 6 weeks. Three major and two minor relapses occurred in five patients at a median of 30 months, which were treated by re-dosing with RTX for major relapses and steroid increase alone for minor relapses. Adverse events included one severe drug reaction, four non-serious and one serious infective episodes in the first 3 months, one skin malignancy at 21 months and one death at 19 months not related to treatment or disease.
A RTX-based low-dose CYP regimen is effective at inducing long-term disease-free remission and may be the platform on which to develop a steroid-minimizing regimen to further decrease adverse events in the future.
Genetic manipulation of cellulose biosynthesis in trees may provide novel insights into the growth and development of trees. To explore this possibility, the overexpression of an aspen secondary ...wall-associated cellulose synthase （PtdCesAS） gene was attempted in transgenic aspen （Populus tremuloides L.） and unexpectedly resulted in silencing of the transgene as well as its endogenous counterparts. The main axis of the transgenic aspen plants quickly stopped growing, and weak branches adopted a weeping growth habit. Furthermore, transgenic plants initially developed smaller leaves and a less extensive root system. Secondary xylem （wood） of transgenic aspen plants contained as little as 10% cellulose normalized to dry weight compared to 41% cellulose typically found in normal aspen wood. This massive reduction in cellulose was accompanied by proportional increases in lignin （35%） and non-cellulosic polysaccharides （55%） compared to the 22% lignin and 36% non-cellulosic polysaccharides in control plants. The transgenic stems pro- duced typical collapsed or ＇irregular＇ xylem vessels that had altered secondary wall morphology and contained greatly reduced amounts of crystalline cellulose. These results demonstrate the fundamental role of secondary wall cellulose within the secondary xylem in maintaining the strength and structural integrity required to establish the vertical growth habit in trees.
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