126 research outputs found

    Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not

    Get PDF
    Comparisons of survival between dialysis and nondialysis care for older adults with kidney failure have been limited to those managed by nephrologists, and are vulnerable to lead and immortal time biases. So we compared time to all-cause mortality among older adults with kidney failure treated vs. not treated with chronic dialysis. Our retrospective cohort study used linked administrative and laboratory data to identify adults aged 65 or more years of age in Alberta, Canada, with kidney failure (2002-2012), defined by two or more consecutive outpatient estimated glomerular filtration rates less than 10 mL/min/1.73m2, spanning 90 or more days. We used marginal structural Cox models to assess the association between receipt of dialysis and all-cause mortality by allowing control for both time-varying and baseline confounders. Overall, 838 patients met inclusion criteria (mean age 79.1; 48.6% male; mean estimated glomerular filtration rate 7.8 mL/min/1.73m2). Dialysis treatment (vs. no dialysis) was associated with a significantly lower risk of death for the first three years of follow-up (hazard ratio 0.59 [95% confidence interval 0.46-0.77]), but not thereafter (1.22 [0.69-2.17]). However, dialysis was associated with a significantly higher risk of hospitalization (1.40 [1.16-1.69]). Thus, among older adults with kidney failure, treatment with dialysis was associated with longer survival up to three years after reaching kidney failure, though with a higher risk of hospital admissions. These findings may assist shared decision-making about treatment of kidney failure

    Personality traits and mental disorders

    Get PDF
    Peer reviewe

    Avant-garde and experimental music

    No full text

    The lure of postwar London:networks of people, print and organisations

    Get PDF

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

    Get PDF
    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    The service economy

    Full text link

    'Vernacular Voices: Black British Poetry'

    Get PDF
    ABSTRACT Black British poetry is the province of experimenting with voice and recording rhythms beyond the iambic pentameter. Not only in performance poetry and through the spoken word, but also on the page, black British poetry constitutes and preserves a sound archive of distinct linguistic varieties. In Slave Song (1984) and Coolie Odyssey (1988), David Dabydeen employs a form of Guyanese Creole in order to linguistically render and thus commemorate the experience of slaves and indentured labourers, respectively, with the earlier collection providing annotated translations into Standard English. James Berry, Louise Bennett, and Valerie Bloom adapt Jamaican Patois to celebrate Jamaican folk culture and at times to represent and record experiences and linguistic interactions in the postcolonial metropolis. Grace Nichols and John Agard use modified forms of Guyanese Creole, with Nichols frequently constructing gendered voices whilst Agard often celebrates linguistic playfulness. The borders between linguistic varieties are by no means absolute or static, as the emergence and marked growth of ‘London Jamaican’ (Mark Sebba) indicates. Asian British writer Daljit Nagra takes liberties with English for different reasons. Rather than having recourse to established Creole languages, and blending them with Standard English, his heteroglot poems frequently emulate ‘Punglish’, the English of migrants whose first language is Punjabi. Whilst it is the language prestige of London Jamaican that has been significantly enhanced since the 1990s, a fact not only confirmed by linguistic research but also by its transethnic uses both in the streets and on the page, Nagra’s substantial success and the mainstream attention he receives also indicate the clout of vernacular voices in poetry. They have the potential to connect with oral traditions and cultural memories, to record linguistic varieties, and to endow ‘street cred’ to authors and texts. In this chapter, these double-voiced poetic languages are also read as signs of resistance against residual monologic ideologies of Englishness. © Book proposal (02/2016): The Cambridge History of Black and Asian British Writing p. 27 of 4

    Whole-genome sequencing reveals host factors underlying critical COVID-19

    Get PDF
    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
    corecore