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Irritable bowel syndrome (IBS) is a prevalent health challenge in a Danish welfare context. Drawing on ethnographic fieldwork at two Danish gastroenterology clinics, and inspired by Charles E. Rosenberg's idea of styles of explaining widespread diseases, we outline three styles of understanding and treating gut trouble in daily clinical work: "The microbial gut," "the mindful gut," and "the lifestyled gut." Moreover, we suggest the concept of fluidity to characterize IBS as a diagnostic category that allows clinicians and patients to operate through complex understandings of permeable boundaries between body, mind, and environment to negotiate personalized solutions for embodied gut sensations. [ABSTRACT FROM AUTHOR]

Across rehabilitation fields, rehabilitees and professionals meet to set rehabilitation goals. Portrayed as an ordinary, yet foundational practice in rehabilitation, participants often find goal-setting meetings challenging; ideal and real seem to clash. Based on a long-term fieldwork in Danish Parkinson's disease rehabilitation, we explore goal-setting and its rationale to gain insight into why goal-setting qualifies as challenging. We find that challenges relate to disease, organizational matters and an imbalance in institutional knowledge, but also that different logics, of choice, interdependence, and accountability, entangle and affect goal-setting. A competitive aspect between goal-setting logics appears pivotal to understand the challenges in goal-setting. [ABSTRACT FROM AUTHOR]

Drawing upon ethnographic fieldwork in a Danish pediatric oncology ward we explore how children – as cancer patients – respond to the time constraints of cancer treatment that may save their lives but simultaneously hold them under a spell of time. Children respond through practices of what we have called "tinkering with time," which enable them to seize control not of life, but of time. We suggest that tinkering be understood as time work through which children mold their experience of the constraints of time. We regard this as an expression of existential agency that simultaneously sustains children's sense of autonomy. [ABSTRACT FROM AUTHOR]

Informal caregiving is increasingly considered a health care delivery-resource within the North European welfare states. While 'informal' often refers to non-professional, 'caregiving' connotes both affective concern (caring about) and practical action (caring for). This duality of meanings, however, often refers to the one direction in which care is given. Care, we suggest, is relational and also requires that people receiving care are able to or wanting to share their needs. Informal caregiving thus requires sharing. Based on 155 semi-structured, narrative interviews with people with lung or bowel cancer, living in Denmark, Sweden or England, this paper explores how and with whom people 'share' when they fall ill. We approach sharing as a heuristic for reflecting on informal-caregiving, and illustrate how being cared for or asking for care are entangled with the management of social risks and notions of selfhood. We conclude that informal caregiving should explicitly be recognised as morally and sympathetically committed practices, which attend to the diversity of local moral worlds of patients, their needs and experiences. [ABSTRACT FROM AUTHOR]

Advances within cancer immunotherapy have fueled a paradigm shift in cancer treatment, resulting in increasing numbers of cancer types benefitting from novel treatment options. Despite originally being considered an immunologically silent malignancy, recent studies encourage the research of breast cancer immunogenicity to evaluate immunotherapy as a treatment strategy. However, the epitope landscape in breast cancer is minimally described, limiting the options for antigen-specific, targeted strategies. Aromatase, never in mitosis A-related kinase 3 (NEK3), protein inhibitor of activated STAT3 (PIAS3), and prolactin are known as upregulated proteins in breast cancer. In the present study, these four proteins are identified as novel T cell targets in breast cancer. From the four proteins, 147 peptides were determined to bind HLA-A*0201 and -B*0702 using a combined in silico/in vitro affinity screening. T cell recognition of all 147 peptide-HLA-A*0201/-B*0702 combinations was assessed through the use of a novel high-throughput method utilizing DNA barcode labeled multimers. T cell recognition of sequences within all four proteins was demonstrated in peripheral blood of patients, and significantly more T cell responses were detected in patients compared to healthy donors for both HLA-A*0201 and -B*0702. Notably, several of the identified responses were directed toward peptides, with a predicted low or intermediate binding affinity. This demonstrates the importance of including low-affinity binders in the search for epitopes within shared tumor associated antigens (TAAs), as these might be less subject to immune tolerance mechanisms. The study presents four novel TAAs containing multiple possible targets for immunotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

Little is known about how people living in the aftermath of cancer treatment experience and manage worries about possible signs of cancer relapse, not as an individual enterprise but as socially embedded management. One-year ethnographic fieldwork was conducted in a coastal village of under 3000 inhabitants in northern Norway. Ten villagers who had undergone cancer treatment from six months to five years earlier were the main informants. During fieldwork, the first author conducted qualitative, semi-structured monthly interviews with them, and participated in their everyday activities and relationships, including families, friends and co-villagers. In this article, we contemplate human emotions as arising in contexts of transactions, capable of creating social realities. By including this perspective, we highlight how people who recover from cancer construct and experience worry about possible relapse in relation to close family members, friends and co-villagers in the socially closely-knit and relatively isolated village. These emotional experiences emerge through relationships with others have communicative characteristics and take place in interaction with the social environment of their village. While informants attempt to protect family members by avoiding sharing worries with them, they express the need to share their worries within friendships. However, they experience both comfort and challenges in managing their worries in relation to acquaintances in the village. Overall, the study enhances understanding of the social embeddedness of emotions in everyday life, by revealing how worries of relapse of cancer configure and relate to various social contexts. [ABSTRACT FROM AUTHOR]

Health care systems as well as bodies of medical knowledge are dynamic and change as the result of political and social transformations. In recent decades, health care systems have been subjected to a whole assemblage of regulatory practices. The local changes undertaken in Denmark that are being explored here are indicative of a long-term shift that has occurred in many welfare states intended to make public services in the Global North more efficient and transparent. Departing in prolonged field work in Danish general practice and the anthropological literature on audit culture, this paper suggests that the introduction of regulatory practices has enhanced the need for triage as a key organising principle. The term triage literally means separating out and refers to the process of sorting and placing patients in time and space. The paper suggests that an increasing introduction of triage feeds into a reconfiguration of diagnostic work, where the clinical setting is gradually becoming more intertwined with the governing domains of policy, and the work of the secretary is gradually becoming more intertwined with that of the doctor. Finally, the paper argues that an increasing regulation of general practice poses an ethically charged challenge to existing welfare politics of responsibility between the state and the public, as it makes it increasingly difficult to negotiate access to care. [ABSTRACT FROM AUTHOR]

Introduction: Analysis of circulating tumor DNA is a promising approach to guide the treatment of cancer patients but despite large efforts it has not been broadly applied in the clinic. Technical obstacles and lack of standardization have hampered the process and it has proved challenging to make highly sensitive analyses available for all patients. Research has focused on the use of somatic mutations but because of large mutational diversity among patients the setup becomes unmanageable for daily routine use. Areas covered: Methylations are key events in cancer development and can be used as markers for the presence of circulating tumor DNA similar to how mutations have been used. This review focuses on analytical aspects and possible clinical applications of methylated ctDNA in plasma from cancer patients. Expert commentary: Technical and clinical challenges of mutation and methylation analyses are similar. However, the possibility to analyze a limited number of methylations present in all tumors of a certain type allows for proper validation and standardization of the analyses. Tumor-specific methylation analyses could supplement or substitute mutation analyses for certain clinical applications and assist the progress of the clinical use of circulating tumor DNA. [ABSTRACT FROM AUTHOR]

In recent years an extensive social gradient in cancer outcome has attracted much attention, with late diagnosis proposed as one important reason for this. Whereas earlier research has investigated health care seeking among cancer patients, these social differences may be better understood by looking at health care seeking practices among people who are not diagnosed with cancer. Drawing on long-term ethnographic fieldwork among two different social classes in Denmark, our aim in this article is to explore the relevance of class to health care seeking practices and illness concerns. In the higher middle class, we predominantly encountered health care seeking resembling notions of health consumerism, practices sanctioned and encouraged by the health care system. However, among people in the lower working class, health care seeking was often shaped by the inseparability of physical, political, and social dimensions of discomfort, making these practices difficult for the health care system to accommodate. [ABSTRACT FROM AUTHOR]

In this article we explore the uncertainties of living in the aftermath of cancer treatment within the context of the Norwegian welfare state. Serious illnesses confront people with the uncertainty of life itself. We suggest that managing this form of existential uncertainty is inherently a social process and their considerations of whether or not to share worries are part of the everyday management of social relationships. We refer to this process of managing uncertainty and the social processes intrinsic to it as an act of ‘balancing’. We draw on data from repeated interviews with eight former cancer patients in a Northern Norwegian city carried between January 2014 and January 2015. Through our inquiry into who was involved in the participants’ interpretation of bodily sensations, health and care seeking, we found that the participants were keeping most of their uncertainties to themselves. Their main argument was that they did not want to make others worry unnecessarily. On the other hand, participants talked about the need and expectation that relevant others had to be informed and involved and the participants also described needing an outlet through being able to share worries. These needs and concerns were balanced within a wish to maintain ‘normal everyday life’ as far as possible. [ABSTRACT FROM AUTHOR]

This paper regards a concern for the quality of analyses made on the basis of qualitative interviews in some parts of qualitative health research. Starting with discussions departing in discussions on studies exploring ‘patient delay’ in healthcare seeking, it is argued that an implicit and simplified notion of causality impedes reflexivity on social context, on the nature of verbal statements and on the situatedness of the interview encounter. Further, the authors suggest that in order to improve the quality of descriptive analyses, it is pertinent to discuss the relationship between notions of causality and the need for contextualization in particular. This argument targets several disciplines taking a qualitative approach, including medical anthropology. In particular, researchers working in interdisciplinary fields face the demands of producing knowledge ready to implement, and such demands challenge basic notions of causality and explanatory power. In order to meet these, the authors suggest an analytic focus on process causality linked to contextualization. [ABSTRACT FROM PUBLISHER]

A number of cytotoxic T-cell epitopes are cryptic epitopes generated from non-conventional sources. these include epitopes that are encoded by alternative open reading frames or in generally non-coding genomic regions, such as introns. We have previously observed a frequent recognition of cryptic epitopes by tumor infiltrating lymphocytes isolated from melanoma patients. Here, we show that such cryptic epitopes are more frequently recognized than antigens of the same class encoded by canonical reading frames. furthermore, we report the presence of T cells speciic for three cryptic epitopes encoded in intronic sequences, as a result of incomplete splicing, in the circulation of melanoma patients. One of these epitopes derives from antigen isolated from immunoselected melanoma 2 (AIM2), while the two others are encoded in an alternative open reading frame of an incompletely spliced form of N-acetylglucosaminyl-transferase V (GNt-V) known as NA17-A. We have detected frequent T-cell responses against AIM2 and NA17-A epitopes in the blood of melanoma patients, both prior and after one round of in vitro peptide stimulation, but not in the circulation of healthy individuals and patients with breast or renal carcinoma. In summary, our indings indicate that the T-cell reactivity against AIM2 and NA17-A in the blood of melanoma patients is extensive, suggesting that-similar to melan A (also known as MART1)-these antigens might be used for immunomonitoring or as model antigens in several clinical and preclinical settings. [ABSTRACT FROM AUTHOR]

Therapeutic strategies to deplete lymphocytes, especially regulatory T cells, in cancer patients have been proposed to increase the benefits of (immuno)chemotherapy. In this study, we explored the influence of temozolomide (TMZ) on different T-cell populations and addressed if the depletion of CD4+ T cells would be associated to the clinical benefits of TMZ. Patients were treated with TMZ (150 mg/m² daily, every two weeks on a 4-week schedule) until disease progression. Changes in T-lymphocyte subsets were characterized by flow cytometry. All patients enrolled in this study had histologically verified unresectable Stage IV melanoma. Objective responses were induced in 12.5% of the patients, while 42.5% of them obtained short-term disease stabilization. The median progression-free survival (PFS) of this patient cohort was 8.7 mo. Lymphopenia (< 0.7 × 109 cells/L, grade 2) developed in 71% of the patients after 3 treatment cycles (∼100 d). The development of grade 2 lymphopenia after the 3rd cycle of therapy positively correlated with clinical outcome (p = 0.01), and was linked, though non-significantly, to prolonged median PFS (303 vs. 200 d). In addition, significant changes in CD8+ T-cell subgroups were observed, notably a shift from naïve T cells toward more differentiated memory T cells. Finally, we demonstrated that specific CD8+ T-cell responses against selected tumor associated antigens (TAA s) were enhanced by the administration of TMZ (p = 0.04), while virus-specific T-cell responses were stable. Thus, immunological monitoring in the course of TMZ treatment might become an important tool for clinical guidance in the future. [ABSTRACT FROM AUTHOR]

In spite of the fact that they occur at high rates, the clinical responses of BRAFV600 mutant metastatic melanoma to BRAF inhibitors are usually short-lasting, with most cases progressing within less than 8 mo. Immunomodulatory strategies initiated after progression have recently been reported to be poorly efficient. By characterizing the immunological interactions between T cells and cancer cells in clinical material as well as the influence of the FDA-approved BRAF inhibitor vemurafenib on the immune system, we aimed at unraveling new strategies to expand the efficacy of adoptive T-cell transfer, which represents one of the most promising approaches currently in clinical development for the treatment of metastatic melanoma. Here we show that blocking the BRAF-MAP K pathway in BRAF signaling-addicted melanoma cells significantly increases the ability of T cells contained in clinical grade tumor-infiltrating lymphocytes to recognize autologous BRAFV600 mutant melanoma cell lines in vitro. Antitumor reactivity was improved regardless of the class of antigen recognized by tumor-specific CD81+ T cells. Microarray data suggests that improved tumor recognition is associated with modified expression of MHC Class I-associated proteins as well as of heat-shock proteins. In conclusion, our preclinical data suggest that an appropriately timed sequential treatment of BRAFV600 mutant melanoma with vemurafenib and adoptive T-cell transfer might result in synergistic antineoplastic effects owing to an increased immunogenicity of cancer cells [ABSTRACT FROM AUTHOR]

Objective. The absence of a more significant improvement in cancer survival in countries such as the UK and Denmark may be partly rooted in delayed care-seeking among cancer patients. Past research on patient delay has mainly focused on patient characteristics (e.g. sociodemographic and psychological factors and symptom recognition) as causes of delayed care-seeking, while few studies have examined how the organizational structure of health care systems may influence patients' reflections on seeking care. The aim of this study was to explore this relationship. Design. The analysis presented is based on semi-structured interviews with 30 cancer patients and their families. Results. The article raises two hypotheses on the relationship between structural elements of a health care system and people's reflections on seeking health care: (1) Gatekeeping introduces an asymmetrical relationship between the patient and the GP which potentially results in self-restricting care-seeking, (2) Continuity in the doctor-patient relationship may negatively influence patient reflections on access to health care, as the focus shifts from the medical issues of the consultation to reflections on how to properly interact with the GP and the system in which she/he is situated. Conclusion. It is concluded that these hypotheses form a sound basis for further primary care research on how the organizational structure of health care systems influences patient reflections on access to medical care. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to develop and validate a high-pressure liquid chromatography (HPLC) method for assessing vitamin D status as 25-hydroxyvitamin D2 (S-25OHD2) and 25-hydroxyvitamin D3 (S-25OHD3) in serum. Material and methods. We assessed the within- and between-subject variation of vitamin D status in serum samples from four different dietary intervention studies in which subjects (n = 92) were supplemented with different doses of vitamin D3 (5-12 µg/day) and for different durations (4-20 months). Results. The HPLC method was applicable for 4.0-200 nmol S-25OHD/L, while the within-day and between-days variations were 3.8 % and 5.7 %, respectively. There was a concentration-dependent difference between results obtained by a commercial radioimmunoassay and results from the HPLC method of -5 to 20 nmol 25OHD/L in the range 10-100 nmol 25OHD/L. The between-subject variation estimated in each of the four human intervention studies did not differ significantly (p = 0.55). Hence, the pooled standard deviation was 15.3 nmol 25OHD3/L. In the studies with 6-8 samplings during 7-20 months of supplementation, the within-subject variation was 3.9-7.2 nmol 25OHD3/L, while vitamin D status was in the range 47-120 nmol/L. Conclusions. The validated HPLC method was applied in samples from human intervention studies in which subjects were supplemented with vitamin D3. The estimated standard deviation between and within subjects is useful in the forthcoming decision on setting limits for optimal vitamin D status. [ABSTRACT FROM AUTHOR]

A male patient with Stage IV melanoma was treated with ipilimumab resulting in a long-lasting partial response according to RECIST criteria. However, twenty months after ipilimumab treatment, routine follow-up CT scan revealed new splenic lesions initially interpreted as indicative of progressive disease. Nevertheless, a biopsy was performed and histologic evaluation showed that the lesions did not contain malignant cells but rather constituted non-caseating epithelioid cell granulomas consistent with sarcoidosis. As the patient was asymptomatic no treatment was initiated and over the following months the splenic lesions slowly disappeared and to date the patient remains in remission. Ipilimumab is now widely used in the treatment of melanoma patients. Our case-report illustrates that physicians should consider the possibility of ipilimumab induced visceral sarcoidosis-like reactions, mimicking metastatic lesions, developing even many months after ipilimumab treatment. Thus, biopsy of such suspicious lesions is advisable to avoid misinterpretation as disease progression and unnecessary resumption of cancer therapy. [ABSTRACT FROM PUBLISHER]