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Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March–September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5–34.4) and 4.2 (1.1–15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.

Background All healthcare professionals working with children should have a child-centred perspective, and should be responsive to children and adolescents who want to talk about their thoughts and feelings. The child's or adolescent's story is the starting point for mutual understanding between them and the healthcare professional, and is the basis for shared decision-making between patients and healthcare professionals in child-centred care. Aim To advance understanding of how Swedish children and adolescents with cancer perceived the effects of the disease and its treatment on their everyday life. Method Ten girls and five boys, aged between five and 18 years, with cancer were interviewed individually using four communication tools. The interviews lasted between 20 and 65 minutes and took place without their parents present. The data were analysed using content analysis. Findings Transition to an unpredictable everyday life was identified as a main theme, with five subthemes: struggling with side effects of the cancer and its treatment; treatment as an 'emotional rollercoaster'; changed self and being vulnerable; changed social life; and concerns about academic achievement. Conclusion To provide effective support and care for children and adolescents with cancer, healthcare professionals should strive to listen to them and focus on their perspectives.

the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival.All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure.A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively.In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.

This paper explores the use of iron in the Late Bronze Age and the earliest Iron Age (c. 1100-300 BC) in south-eastern Sweden, with a focus on the final Bronze Age and Pre-Roman Iron Age I. The aim is to study how early iron was used, valued and perceived, particularly in relation to pre-existing bronze and gold. Choosing iron for certain object types, such as dress attributes and arm rings, and in key symbols, notably the spiral, suggests an appreciation for its metallic shine and colour in contrast to bronze. This silvery lustre was in some cases exploited intentionally, and may sometimes have been associated with the moon in a celestial mythology. The lunar connection might have been accentuated by the origin of iron from bodies of water, which were surrounded by strong beliefs and were often the focus of sacrificial depositions in this period. The qualities sought after in iron during the Bronze Age-Iron Age transition were in some ways different from those appreciated later in Iron Age and historical times. It is necessary to further consider early iron in its contemporary setting without comparison to the 'successful' adaptation in the late Pre-Roman Iron Age onwards.

Traces of bronze casting – fragmented moulds and crucibles - frequently occur at Late Bronze Age settlements. These traces are often assumed to represent utilitarian domestic production, in contrast to more specialised workshop production at ritual or elite locations. Moreover, settlements have often been reduced to overall production units, while actual arrangements of bronze casting within sites has remained unexplored. The aim of this paper is to provide new insight into the organization of metalworking from an empirical and ‘bottom up’ perspective by examining the spatial and social contexts of bronze casting. The analysis draws on ten excavated sites in south-eastern Sweden and addresses three spatial levels: site, setting and framing. The study shows that domestic arenas often hosted varied and complex metalworking staged at various indoor and outdoor hearths located in the core areas of settlements. Rather than being conceptualized as levels, the organization of Late Bronze Age metalworking was a multifaceted, communicative and user-oriented practice. These insights have consequences for excavation methods as well as for the interpretation of the role of metalworking in society

HLA-B*08:181 differs from HLA-B*08:01:01:01 in codon 94, 95, 97 and 99 of exon 3.In this report, the HLA‐B*08:181 allele, will be described. The novel allele was found in a potential unrelated dono ...

Specific IgM, administered together with the antigen it recognizes, enhances primary antibody responses, formation of germinal centers, and priming for secondary antibody responses. The response to all epitopes on the antigen to which IgM binds is usually enhanced. IgM preferentially enhances responses to large antigens such as erythrocytes, malaria parasites, and keyhole limpet hemocyanine. In order for an effect to be seen, antigens must be administered in suboptimal concentrations and in close temporal relationship to the IgM. Enhancement is dependent on the ability of IgM to activate complement, but the lytic pathway is not required. Enhancement does not take place in mice lacking complement receptors 1 and 2 (CR1/2) suggesting that the role of IgM is to generate C3 split products, i.e., the ligands for CR1/2. In mice, these receptors are expressed on follicular dendritic cells (FDCs) and B cells. Optimal IgM-mediated enhancement requires that both cell types express CR1/2, but intermediate enhancement is seen when only FDCs express the receptors and low enhancement when only B cells express them. These observations imply that IgM-mediated enhancement works through several, non-mutually exclusive, pathways. Marginal zone B cells can transport IgM-antigen-complement complexes, bound to CR1/2, from the marginal zone and deposit them onto FDCs. In addition, co-crosslinking of the BCR and the CR2/CD19/CD81 co-receptor complex may enhance signaling to specific B cells, a mechanism likely to be involved in induction of early extrafollicular antibody responses.

Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

‘Workshops’ and ‘workshop production’ are central to archaeological understanding of metalworking in Bronze Age societies. In this article the concept of workshops is used as a starting point to review preconceptions about the social and spatial organisation of bronze crafting, focusing particularly on how it influences expectations of crafting evidence in the archaeological record. It argues that assumptions of a permanent, customised crafting place hosting the full manufacturing process, as often implied by the term ‘workshop’, are unsuitable for understanding the nature of bronze crafting in southern Scandinavia during the Late Bronze Age. Instead, drawing on evidence from south-eastern Sweden, the craft is characterised as flexible, embedded, and multi-locational. Furthermore, differences in crafting loci between ornaments and weapons are suggested to relate to the initiations of their intended bearers and to demonstrate the heterogeneous organisation of prestige goods production. Such user-oriented production provides an interesting example of the organisation of elite-motivated crafting outside the context of centralised states.

Specific IgM, administered together with the antigen it recognizes, enhances primary antibody responses, formation of germinal centers, and priming for secondary antibody responses. The response to all epitopes on the antigen to which IgM binds is usually enhanced. IgM preferentially enhances responses to large antigens such as erythrocytes, malaria parasites, and keyhole limpet hemocyanine. In order for an effect to be seen, antigens must be administered in suboptimal concentrations and in close temporal relationship to the IgM. Enhancement is dependent on the ability of IgM to activate complement, but the lytic pathway is not required. Enhancement does not take place in mice lacking complement receptors 1 and 2 (CR1/2) suggesting that the role of IgM is to generate C3 split products, i.e., the ligands for CR1/2. In mice, these receptors are expressed on follicular dendritic cells (FDCs) and B cells. Optimal IgM-mediated enhancement requires that both cell types express CR1/2, but intermediate enhancement is seen when only FDCs express the receptors and low enhancement when only B cells express them. These observations imply that IgM-mediated enhancement works through several, non-mutually exclusive, pathways. Marginal zone B cells can transport IgM-antigen-complement complexes, bound to CR1/2, from the marginal zone and deposit them onto FDCs. In addition, co-crosslinking of the BCR and the CR2/CD19/CD81 co-receptor complex may enhance signaling to specific B cells, a mechanism likely to be involved in induction of early extrafollicular antibody responses.

Lack of complement factors C1q, C2, C3, or C4, but not of factor B in the alternative pathway or of mannane binding lectin (MBL) in the lectin pathway, leads to severe impairment of primary antibody responses (reviewed in. Because C1q is only used in classical pathway activation, these observations suggest that only this pathway is involved in antibody responses. An efficient classical pathway activator is IgM. Specific IgM, passively administered together with suboptimal doses of the antigen it recognizes, induces a stronger antibody response than does the antigen alone. This article is protected by copyright. All rights reserved.