Sarah Li

T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

BACKGROUND: Toll-like receptors (TLRs) are essential components of the immune response to fungal pathogens. We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients of allogeneic hematopoietic-cell transplants. METHODS: We analyzed 20 single-nucleotide polymorphisms (SNPs) in the toll-like receptor 2 gene (TLR2), the toll-like receptor 3 gene (TLR3), the toll-like receptor 4 gene (TLR4), and the toll-like receptor 9 gene (TLR9) in a cohort of 336 recipients of hematopoietic-cell transplants and their unrelated donors. The risk of invasive aspergillosis was assessed with the use of multivariate Cox regression analysis. The analysis was replicated in a validation study involving 103 case patients and 263 matched controls who received hematopoietic-cell transplants from related and unrelated donors. RESULTS: In the discovery study, two donor TLR4 haplotypes (S3 and S4) increased the risk of invasive aspergillosis (adjusted hazard ratio for S3, 2.20; 95% confidence interval [CI], 1.14 to 4.25; P=0.02; adjusted hazard ratio for S4, 6.16; 95% CI, 1.97 to 19.26; P=0.002). The haplotype S4 was present in carriers of two SNPs in strong linkage disequilibrium (1063 A/G [D299G] and 1363 C/T [T399I]) that influence TLR4 function. In the validation study, donor haplotype S4 also increased the risk of invasive aspergillosis (adjusted odds ratio, 2.49; 95% CI, 1.15 to 5.41; P=0.02); the association was present in unrelated recipients of hematopoietic-cell transplants (odds ratio, 5.00; 95% CI, 1.04 to 24.01; P=0.04) but not in related recipients (odds ratio, 2.29; 95% CI, 0.93 to 5.68; P=0.07). In the discovery study, seropositivity for cytomegalovirus (CMV) in donors or recipients, donor positivity for S4, or both, as compared with negative results for CMV and S4, were associated with an increase in the 3-year probability of invasive aspergillosis (12% vs. 1%, P=0.02) and death that was not related to relapse (35% vs. 22%, P=0.02). CONCLUSIONS: This study suggests an association between the donor TLR4 haplotype S4 and the risk of invasive aspergillosis among recipients of hematopoietic-cell transplants from unrelated donors.

BACKGROUND: Dignity has become a central concern in UK health policy in relation to older and vulnerable people. The empirical and theoretical literature relating to dignity is extensive and as likely to confound and confuse as to clarify the meaning of dignity for nurses in practice. The aim of this paper is critically to examine the literature and to address the following questions: What does dignity mean? What promotes and diminishes dignity? And how might dignity be operationalised in the care of older people?This paper critically reviews the theoretical and empirical literature relating to dignity and clarifies the meaning and implications of dignity in relation to the care of older people. If nurses are to provide dignified care clarification is an essential first step. METHODS: This is a review article, critically examining papers reporting theoretical perspectives and empirical studies relating to dignity. The following databases were searched: Assia, BHI, CINAHL, Social Services Abstracts, IBSS, Web of Knowledge Social Sciences Citation Index and Arts & Humanities Citation Index and location of books a chapters in philosophy literature. An analytical approach was adopted to the publications reviewed, focusing on the objectives of the review. RESULTS AND DISCUSSION: We review a range of theoretical and empirical accounts of dignity and identify key dignity promoting factors evident in the literature, including staff attitudes and behaviour; environment; culture of care; and the performance of specific care activities. Although there is scope to learn more about cultural aspects of dignity we know a good deal about dignity in care in general terms. CONCLUSION: We argue that what is required is to provide sufficient support and education to help nurses understand dignity and adequate resources to operationalise dignity in their everyday practice. Using the themes identified from our review we offer proposals for the direction of future research.

This article is part of a larger study which presents findings from an in‐depth longitudinal case study of a student’s Ph.D. journey. It shows how criticism is produced and managed in the supervisory relationship. As well as an overview of types of criticism produced across a range of supervisory interactions, the article presents a micro‐analysis of two recorded interactions between a supervisor and a Ph.D. student. Moments of interactional difficulty, disagreement and the strategic abandonment of conflict‐producing dialogue are described. Through the strategies of foreshadowing, advice‐giving, repair, humour and politeness, a symbiotic and cordial relationship is collaboratively developed and sustained. The effective management of criticism is a joint activity that underlies the capacity for supervision to be educationally effective. The findings of this study will contribute to the development of training programmes in supervisory skills in higher education, as well as advising students on how to get the most out of supervisors.