| 1. |
- Arman Rehnsfeldt, Maria, 1954-, et al.
(författare)
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Suffering related to health care : a study of breast cancer patients' experiences.
- 2004
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Ingår i: International Journal of Nursing Practice. - 1322-7114 .- 1440-172X. ; 10:6, s. 248-256
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Tidskriftsartikel (refereegranskat)abstract
- A previous study indicated that patient narratives include experiences of suffering caused or increased by health-care encounters. The aim of this study was to interpret and understand the meaning of patients' experiences of suffering related to health care from an ethical, existential and ontological standpoint. Sixteen women with breast cancer in Sweden and Finland took part in qualitative interviews analysed with a hermeneutic, interpretive approach. The outcome showed that suffering related to health care is a complex phenomenon and constitutes an ethical challenge to health-care personnel. The women's experiences of suffering related to health care tended to be of similar seriousness as their experiences of suffering in relation to having cancer. In an ethical, existential and ontological sense, suffering related to health care is basically a matter of neglect and uncaring where the patient's existential suffering is not seen and she is not viewed as a whole human being.
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| 2. |
- Fredriksson, Lennart, et al.
(författare)
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The ethics of the caring conversation
- 2003
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Ingår i: Nursing Ethics. - : SAGE Publications. - 0969-7330 .- 1477-0989. ; 10:2, s. 138-148
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to explore the ethical foundations for a caring The analysis is based on the ethics of Paul Ricoeur and deals with questions such as what kind of person the nurse ought to be and how she or he engages in caring conversations with suffering others. According to Ricoeur, ethics (the aim of an accomplished life) has primacy over morality (the articulation of aims in norms). At the ethical level, self-esteem and autonomy were shown to be essential for a person (nurse) to act with respect and responsibility. The ethical relationship of a caring conversation was found to metrical, because of the passivity inflicted by suffering. This asymmetry was found to be potentially unethical if not balanced with reciprocity. In the ethical context, the caring conversation is one in which the nurse makes room through the ethos of caritas for a suffering person to regain his or her self-esteem, and thus makes a good life possible.
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| 3. |
- Frilund, Marianne, et al.
(författare)
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Assessment of ethical ideals and ethical manners in care of older people
- 2013
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Ingår i: Nursing Research and Practice. - : Hindawi Publishing Corporation. - 2090-1429 .- 2090-1437. ; , s. Article ID 374132-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to establish structured clusters and well-defined ontological entities (nodes) describing ethical values as both ideal and opportunity for ethical manner as perceived by the caregiver. In this study, we use Bayesian Belief Networks (BBNs) to analyse ethical values (ethos) and ethical manners in daily work with older people. Material is based on questionnaire data collected by the instrument for the self-assessment of individual ethos in the care of older people (ISAEC) in spring 2007 in a municipality in Western Finland. This study is unique in its kind, both concerning the selected approach and methodological questions. BBNs have not been used significantly in nursing research, nor are there any studies that examine the ethical possibilities with focus on the probable effects upon changing conditions.
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| 4. |
- Hilli, Yvonne Elisabet, et al.
(författare)
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Idéhistoria som metod
- 2008
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Ingår i: Hoitotiede. - 0786-5686. ; 20:6, s. 345-353
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Tidskriftsartikel (refereegranskat)
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| 5. |
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| 6. |
- Hilli, Yvonne, 1959-, et al.
(författare)
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The Home as Ethos of Caring - a concept determination
- 2017
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Ingår i: Nursing Ethics. - : SAGE Publications. - 0969-7330 .- 1477-0989.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Within nursing, the concepts of home and homelike have been used indiscriminately to describe characteristics of health care settings that resemble a home more than an institution.Objectives: The aim of this study was to investigate the concept of home (hem in Swedish). The main questions were as follows: What does the concept of home entail etymologically and semantically? Of what significance is the meaning of the concept to caring science and nursing?Design and methods: This study had a qualitative design with a hermeneutical approach guided by Gadamer. Eriksson’s model of concept determination was partly used to determine the etymology and semantics, the essence and epistemic category of the concept of home. In this study, etymological dictionaries and 17 Swedish language dictionaries published between 1850 and 2001 were investigated.Findings: The home, framed as the ethos of caring, can be drawn as a three-dimensional picture where the three dimensions have a common core, enclosed and inviolable. Symbolically, the picture of home can be seen as the ethos of the human being’s innermost room, the human being’s manner of being and the tone cxpressed in the external or abstract room where the human being lives and interacts with others.Conclusions: Based on the findings in this study we conclude that home as ethos is an inner ethical dimension within the human being. Human beings who are in contact with their ethos, the self, feel at home and dare to follow the voice of their heart. Nurses who experience at-homeness have an ability to invite the patient into a caring relationship. The home and the feeling of being at home have significant meaning in terms of human beings’ health and well-being.
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| 7. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 8. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
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| 11. |
- Ljungquist, Marie, 1954-
(författare)
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Vårdande gärningar och vanor för en caritativ hållning i den vårdande akten
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The research interests address a need for knowledge regarding the importance of 'acts of caring' for a caritative approach when performing tasks in the care of the elderly. The overall aim of the research was to deepen the understanding of ethics and describe the actions and habits that are important in the 'acts of caring' for both patients and caregivers in relation to the caritative nursing and ethics of care relevant to the caritative care theory. The design of the study design is based on and from a human-scientific perspective and founded on a hermeneutic tradition based on Gadamer's philosophy. Data was collected partly from qualitative interviews with patients and caregivers and partly from a questionnaire for caregivers. The interviews were carried out in several home healthcare contexts. The data has been analysed and interpreted by means of qualitative content analysis. The result shows that the caregiver's caring and non-caring deeds have significance for caregiving and this is manifested in the caregiver's attitude, consciously or unconsciously. And it also shows that repetition results in either good habits or bad habits. With caritative ethics of care, good habits appear that alleviate suffering and promote health in an 'act of caring'. Bad habits, which lead to bad deeds, have no place in the ethics of care and nursing theory, because a non-caring deed cannot create an 'act of caring'. All forms of caring deeds and good habits can be connected to the character traits, virtues and moral integrity of the caregiver, and intertwine in such a way that the good habits of care may arise from another good habit or lead to a new good habit.
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| 12. |
- Middha, Pooja K., et al.
(författare)
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A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
- 2023
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Ingår i: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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| 13. |
- Rehnsfeldt, Arne, 1949-, et al.
(författare)
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The progression of suffering implies alleviated suffering
- 2004
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 18:3, s. 264-272
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of research focusing directly on both patients' suffering and alleviated suffering in relation to care. The aim of this paper was to investigate the progression of suffering in relation to the encounter between the suffering person and the caregiver from the perspective of an understanding of life. The progression of suffering is assumed to be an existential 'sign' of the development of understanding of life as an ontological or spiritual entity, which demands a meaning-creating encounter between the patient and caregiver. The concept 'existential caring encounter' was used to describe how the encounter between patient and caregiver can create meaning in communion and thereby alleviate suffering by making it bearable. The study was carried out using an interpretive, hermeneutic approach. The study as a whole comprises three parts, and these include letter-writing and interviews. The findings are described by the following main theses: (a) a darkness in life understanding is existentially experienced as unbearable suffering and requires an encounter involving attentive care and confrontation, (b) the turning point means that the struggle of suffering begins, and (c) the encounter involves being meaningcreating in a communion in the struggle of suffering. An understanding of the patterns of unbearable and bearable suffering can be of help to the caregiver in caring for the patient by serving as a basis for meaning-creation in communion. This may thereby be a way of alleviating the patient's suffering by making it bearable during the progression of suffering.
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| 14. |
- Roxberg, Åsa, 1953-, et al.
(författare)
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The meaning of consolation as experienced by nurses in a home-care setting
- 2008
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Ingår i: Journal of Clinical Nursing. - Chichester : Wiley-Blackwell. - 0962-1067 .- 1365-2702. ; 17:8, s. 1079-1087
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Tidskriftsartikel (refereegranskat)abstract
- Aims and objective. The aim of this study was to illuminate nurses’ experiences of consolation and how these experiences relate to suffering and care.Background. Consolation is commonly associated with the relief of suffering. The question of consolation in terms of its definition and relevance for care has, however, been a matter of discussion among nurse researchers. The question raised concerns about the nature of consolation, its place and its role in relation to care and the caring sciences.Design. An explorative qualitative interview study with 12 participants, six registered and six enrolled nurses, was carried out in a home-care context.Methods. A phenomenological-hermeneutic method inspired by the French philosopher Paul Ricoeur was used for the text analysis.Results. Two main aspects of consolation appeared: ‘the present consolation’, which is flexible, sustaining and opening and ‘the absent consolation’, which conceals the suffering and is incapable of consoling. The result was interpreted from a philosophical-ethical perspective, based on the works of Levinas and Lögstrup.Conclusions. Consolation appears as a complex phenomenon, both in terms of its existence and its absence consolation, constituting a caring and non-caring consolation. A caring consolation entails meeting the other as different and being present in a way that gives the other space to be the one he or she really is. It requires acceptance, accepting the sufferer and his/her way of suffering as unique.Relevance to clinical practice. The clinical nurse is involved in complex care situations, which entails both reflecting upon and using intuition when consoling. A caring consolation is a contradictory phenomenon that requires a nurse to be capable of both reflecting upon and acting intuitively on the unique suffering of the other. © 2008 Blackwell Publishing Ltd.
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| 15. |
- Roxberg, Åsa
(författare)
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Vårdande och icke-vårdande tröst
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med avhandlingen är att, ur ett vårdvetenskapligt, och ett i detta inkluderat vårdteologiskt per- spektiv, belysa innebörden av fenomenet tröst och hur tröst förhåller sig till lidande och vård. Det görs i två empiriska intervjustudier med vårdare och äldre vårdtagare samt en tredje delstudie som analyse- rar tröst såsom den framstår i Jobs bok i Gamla testamentet. Dessa delstudier behandlar vårdares upp- levelse av tröst och att trösta, äldre vårdtagares upplevelse av tröst samt Jobs upplevelse av tröst.Metodologiskt har forskningen sin utgångspunkt i fenomenologi och hermeneutik. En fenomenolo- gisk-hermeneutisk metod, inspirerad av Paul Ricoeur, har använts för textanalyserna. I avhandlingen behandlas också det som är signifikant för poetisk och religiös text. De metaforer som förekommer i de empiriska delstudierna med vårdare och äldre analyseras för att ta tillvara det överskott av mening som metaforer, enligt Ricoeur, kan uttrycka.Resultatet visar fem övergripande innebörder: Den motsägelsefulla trösten, Den sammanbindande trösten, Den stumma trösten, Den okontrollerade trösten och Den vilsamma trösten. En vårdande tröst är motsägelsefull såtillvida att den innebär dels att den lidande överlämnar sitt lidande till någon an- nan, dels att lidandet kan ges tillbaka för att lidas. Tröst kan således vara att lida. En sammanbindande tröst är närvarande, d.v.s. är hos den lidande och utgår från dennes lidande. Denna tröst kännetecknas av djup gemenskap, en upplevelse av att vara förstådd på ett djupare sätt. Resultatet visar också en tröst som är stum. Denna tröst svarar inte an på den lidandes upplevelse av sitt lidande, är oformlig och saknar följsamhet för lidandet. Ett exempel på en stum och icke-vårdande tröst är vännernas tröst i Jobs bok. Denna tröst förmår inte trösta därför att den inte är där Job är, d.v.s. i hans upplevelse av sitt lidande. Vidare framstår en vårdande tröst som okontrollerad därför att den dels är spontan, dels bistår den lidande att släppa kontrollen över lidandet. Att släppa kontrollen innebär bl.a. att den lidande ger upp försöken att förstå lidandet för att istället låta det oförståeliga vara oförståeligt. Genom att ge upp det som på olika sätt binder lidandet infinner sig en tröstande och hälsobringande vila i eller från li- dandekampen.Resultatet som helhet tolkas ur ett vårdvetenskapligt perspektiv som vårdgemenskap, tro, hälsa och offer. Tröst som hälsa förstås utifrån en teoretisk modell, inspirerad av Katie Erikssons ontologiska hälsomodell. Filosofiskt-etiskt belyses forskningen utifrån företrädesvis Emmanuel Levinas. Resultatet diskuteras i förhållande till tidigare forskning och i förhållande till vårdvetenskap, samhälle och vård.
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| 16. |
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| 17. |
- Rudolfsson, Gudrun, 1948-, et al.
(författare)
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The development of caring in the perioperative culture : Nurse leaders' perspective on the struggle to retain sight of the patient
- 2007
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Ingår i: Nursing Administration Quarterly. - 0363-9568 .- 1550-5103. ; 31:4, s. 312-324
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Tidskriftsartikel (refereegranskat)abstract
- This article focuses on Swedish nurse leaders and is aimed at achieving a more complete and differentiated understanding of what constitutes caring in the perioperative culture as well as their knowledge and responsibility for the development of caring. Interviews with open-ended questions were conducted with 10 nurse leaders, in which they described their experiences of developing perioperative caring. The interpretation process was based on Gadamer's philosophy of hermeneutics. The findings indicate that developing a perioperative caring culture is a struggle to retain sight of the patient, a process that includes the following 6 phases: (1) when the nurse leaders understood perioperative caring as a process, the nurse's and patient's shared world became obvious to them; (2) safeguarding the patient's position as a unique human being; (3) safeguarding the nurse's welfare by creating a compassionate atmosphere; (4) promoting an idea means never giving up; (5) attaching importance to being trustworthy; and (6) being involved in a dynamic interaction, comprising communion and reciprocity. The most important goal of nursing leadership is to safeguard the welfare of the suffering patient and the relationship between the nurse leader and nursing staff, based on the motive of caritas derived from the idea of humanistic caring.
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| 18. |
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| 19. |
- Rudolfsson, Gudrun, et al.
(författare)
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The perioperative dialogue : holistic nursing in practice
- 2007
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Ingår i: Holistic Nursing Practice. - 0887-9311 .- 1550-5138. ; 21:6, s. 292-298
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Tidskriftsartikel (refereegranskat)abstract
- This article is a synthesis of 2 qualitative studies focusing on patients', anesthetists', and operating-room nurses' experiences of the perioperative dialogue and employing grounded theory as the method of analysis. The aim of the synthesis was to achieve a new holistic understanding of health in the perioperative dialogue. The synthesis highlights the importance of being in communion in a continuous whole due to continuity of care for the creation of health in both patients and nurses.
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| 20. |
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| 21. |
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| 22. |
- Sandvik, Ann-Helén, 1966-, et al.
(författare)
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Understanding and formation : the essence in becoming a caring nurse
- 2018
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Ingår i: https://elsevier.conference-services.net/secureProgramme.asp?conferenceID=4188&uID=830778. - Vikby.
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Konferensbidrag (refereegranskat)abstract
- Understanding and formation - the essence in becoming a caring nurseA-H. Sandvik*2,3, K. Eriksson2, Y. Hilli1,31Novia university of applied sciences, Finland, 2Åbo Akademi University, Finland, 3BoråsUniversity, SwedenIntroduction: Nurse education most often focus on a linear problem-solving process,exemplifying a narrow, technical rationality (Benner & Sutphen 2007). In other words, attentionis largely given to tasks or technical skills (Mulcahy 2011), while the focus rather should be ondeveloping students' understanding (Gustavsson 2011). There is need for a new approach thattargets the processes of becoming and supports identity formation, with the key purpose ofdeveloping professional ways of being, rather than simply knowledge and skills (Dall’Alba2009).Aim: The aim was to clarify the meaning and essence of understanding, as well as to exploreand deepen the understanding of student nurses' processes of understanding and becoming,with the intention of developing a theory model for caring didactics.Methods: The study had a hermeneutical approach and was based on qualitative andquantitative data. The study was longitudinal and followed the students at three universitiesthroughout the education.Findings: Understanding was perceived as an unlimited, endless movement, which can beillustrated as a lemniscate, i.e. a lying eight. Seeing, knowing and becoming are the warpthreads that constitutes the lemniscate. These interwoven threads run throughout the sevenstages of the lemniscate. The infinite spiral movement leads to an ever-increasing degree offormation (Bildung). The lemniscate of understanding circles around two hubs, ethos and arête.A caring culture encloses the lemniscate of understanding, it provides the life space ofunderstanding, and the prevailing basic values are expressed in the culture of the learningspace.Conclusion: Learning and understanding is a process of formation (Bildung). It is not merelylearning and training, but having the opportunity and space to grow into the person one is meantto be. It is not sufficient to confine education to mediation of knowledge and technical skills,whereas true understanding and learning involves a transformation of oneself as a person.There is a need to emphasize this and give it a more prominent position in the nursingeducation.References:Benner, P., & Sutphen, M. (2007). Learning across the professions: The clergy, a case in point.Journal of Nursing Education, 46(3), 103-108.Dall’Alba, G. (2009). Learning to be professionals. Dordrecht: Springer.Gustavsson, B. (2011). Att humanisera och demokratisera utbildning. [To humanize anddemocratize education]. In M. Jensen (Ed.), Lärandets grunder. [The basis for learning] (pp.237-251). Lund: Studentlitteratur.Mulcahy, D. (2011). Teacher professional becoming: A practice-based, actor-network theoryperspective. In L. Scanlon (Ed.), 'Becoming' a professional: An interdisciplinary analysis ofprofessional learning (pp. 219-244). Dordrecht: Springer.Keywords: understanding, becoming, Bildung, formation
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| 23. |
- Söderlund, Maud, et al.
(författare)
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The role of interpretation in caring science
- 2006
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Ingår i: International journal for human caring. - 1091-5710. ; 10:3, s. 30-37
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Tidskriftsartikel (refereegranskat)abstract
- This article focuses a hermeneutic approach on existential interpretation. The methodology is in focus of this article, while a caring science paradigm serves both as a background and as a theoretical framework - as a paradigmatic thinking using an abductive process. The result of the study indicates that the relatives´ experiences give substance to the drama of suffering and health as their situation metaphorically can be described: ’As if struck by a hurricane` but also: `As if resting in the eye of the hurricane` when a terra caritatis is created by the professional caregiver and the suffering can be alleviated.
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| 24. |
- von Tottleben, Malte, et al.
(författare)
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An Integrated Care Platform System (C3-Cloud) for Care Planning, Decision Support, and Empowerment of Patients With Multimorbidity: Protocol for a Technology Trial
- 2022
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Ingår i: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an increasing need to organize the care around the patient and not the disease, while considering the complex realities of multiple physical and psychosocial conditions, and polypharmacy. Integrated patient-centered care delivery platforms have been developed for both patients and clinicians. These platforms could provide a promising way to achieve a collaborative environment that improves the provision of integrated care for patients via enhanced information and communication technology solutions for semiautomated clinical decision support.Objective: The Collaborative Care and Cure Cloud project (C3-Cloud) has developed 2 collaborative computer platforms for patients and members of the multidisciplinary team (MDT) and deployed these in 3 different European settings. The objective of this study is to pilot test the platforms and evaluate their impact on patients with 2 or more chronic conditions (diabetes mellitus type 2, heart failure, kidney failure, depression), their informal caregivers, health care professionals, and, to some extent, health care systems.Methods: This paper describes the protocol for conducting an evaluation of user experience, acceptability, and usefulness of the platforms. For this, 2 “testing and evaluation” phases have been defined, involving multiple qualitative methods (focus groups and surveys) and advanced impact modeling (predictive modeling and cost-benefit analysis). Patients and health care professionals were identified and recruited from 3 partnering regions in Spain, Sweden, and the United Kingdom via electronic health record screening.Results: The technology trial in this 4-year funded project (2016-2020) concluded in April 2020. The pilot technology trial for evaluation phases 3 and 4 was launched in November 2019 and carried out until April 2020. Data collection for these phases is completed with promising results on platform acceptance and socioeconomic impact. We believe that the phased, iterative approach taken is useful as it involves relevant stakeholders at crucial stages in the platform development and allows for a sound user acceptance assessment of the final product.Conclusions: Patients with multiple chronic conditions often experience shortcomings in the care they receive. It is hoped that personalized care plan platforms for patients and collaboration platforms for members of MDTs can help tackle the specific challenges of clinical guideline reconciliation for patients with multimorbidity and improve the management of polypharmacy. The initial evaluative phases have indicated promising results of platform usability. Results of phases 3 and 4 were methodologically useful, yet limited due to the COVID-19 pandemic.
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| 25. |
- Wiklund Gustin, Lena, 1960-, et al.
(författare)
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The drama of suffering as narrated by patients who have undergone coronary bypass surgery
- 2009
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Ingår i: International Journal for Human Caring. - Harrisburg, USA : IAHC. - 1091-5710. ; 13:4, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- The struggle with suffering can be said to be at the centre of what can metaphorically be described as a drama. The study aims to establish whether the drama of suffering is conducted on different levels of health and suffering, and if so, to describe this suffering. Data was analysed using a narrative hermeneutic approach. The analysis revealed four different kinds of drama of suffering. They are described in terms of tragic, romantic, satiric or comic drama – the differences between them relating to different levels of health and suffering and to what the sufferer has to sacrifice to relieve suffering.
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| 26. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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