| 1. |
- Balk, Lennart, et al.
(författare)
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Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
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| 2. |
- Dellve, Lotta, 1965, et al.
(författare)
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Ledarskap i äldreomsorgen: Att leda integrerat värdeskapande i en röra av värden och förutsättningar
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det övergripande syftet med denna rapport är att beskriva chefers etiska värderingar, dilemman och organisatoriska förutsättningar för att bedriva ett värdebaserat ledarskap i såväl kommunal som privat äldreomsorg. Det empiriska materialet består av en omfattande enkätstudie till nästan 500 studerande inom ramen för den nationella ledarutbildningen för chefer inom äldreomsorgen vid Högskolan i Borås under perioden 2013 till 2015. Utbildningen gavs på uppdrag av Socialstyrelsen och omfattade 30 högskolepoäng med två års studier på kvartsfart. Samtliga studerande var yrkesverksamma som chefer och ledare inom kommunal eller privat äldreomsorg i södra Sverige. Metoder som använts i bearbetning och analys av materialet är deskriptiva, jämförande och analytiska med regressionsmodeller och SEM-analys. Resultatet visar på att cheferna – oavsett utbildningsbakgrund, värderade följande etiska värden högst: att inte skada, respekt för individen och rätten till konfidentialitet. Värdedilemman i chefsarbetet är dock vanligt och sammanlänkat med andra utmaningar i arbetet, särskilt med utmaningar som rör hantering över organisationsnivåer (buffertproblem och containerproblem) och av olika ansvarsområden (logikkonflikter). Inom privat verksamhet skattade de medverkande cheferna värdekonflikter och andra utmaningar i lägre grad än chefer inom kommunal verksamhet. De flesta chefer var nöjda med hur de kunde fullfölja sitt ansvar för utveckling av verksamheten avseende värdegrund, kvalitet, processer, dagligt arbete, brukarmedverkan, brukarsäkerhet och arbetsmiljö. De flesta skattade också att de arbetade i mycket hög grad med strukturering och utveckling av dessa frågor. Stödresurser minskade upplevelsen av värdekonflikter, men det fanns skillnad i betydelsen relaterat till chefers grundprofession. Det organisatoriska stödet var också tydligare för chefer inom privat verksamhet. Organiserade stödresurser hade stor betydelse för hållbart integrerat och värdeskapande ledarskap samt för aktiva ledningsstrategier. Även sambandet mellan hållbart ledarskap och aktiva ledarstrategier modererades av grundprofession, där sambandet var moderat negativt för chefer med social grundutbildning. Det tycks således finnas ett utbildningsbehov bland äldreomsorgens chefer och behov av ett utvecklat stöd från arbets- givaren då det varierar avseende omfattning, inriktning och nivå mellan kommunal och privat verksamhet. Sammanfattningsvis har chefer i äldreomsorgen många olika värden, på olika nivåer och utifrån olika perspektiv att förhålla sig till i sitt ledarskap. Att hantera och utveckla förståelse för dessa är utmanande i chefskapet och värdedilemman är vanliga. Majoriteten av cheferna i denna studie beskriver dock generellt en aktiv och god hantering och organisering av dessa. Konstateras att en integrerad förståelse och hantering, samt goda organisatoriska stödresurser tycks bidra till mer hållbart och värdeskapande ledarskap.
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| 3. |
- Karlsson, Anna K, et al.
(författare)
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Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.
- 2015
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Ingår i: Oncotarget. - 1949-2553. ; 6:26, s. 22028-22037
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Tidskriftsartikel (refereegranskat)abstract
- Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3-9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions.
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| 4. |
- Karlsson, O. Andreas, et al.
(författare)
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Design of a PDZbody, a bivalent binder of the E6 protein from human papillomavirus
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection by high risk human papillomavirus (HPV) strains may lead to cancer. Expression of the two viral oncoproteins E6 and E7 is largely responsible for immortalization of infected cells. The HPV E6 is a small (approximately 150 residues) two domain protein that interacts with a number of cellular proteins including the ubiquitin ligase E6-associated protein (E6AP) and several PDZ-domain containing proteins. Our aim was to design a high-affinity binder for HPV E6 by linking two of its cellular targets. First, we improved the affinity of the second PDZ domain from SAP97 for the C-terminus of HPV E6 from the high-risk strain HPV18 using phage display. Second, we added a helix from E6AP to the N-terminus of the optimized PDZ variant, creating a chimeric bivalent binder, denoted PDZbody. Full-length HPV E6 proteins are difficult to express and purify. Nevertheless, we could measure the affinity of the PDZbody for E6 from another high-risk strain, HPV16 (K-d = 65 nM). Finally, the PDZbody was used to co-immunoprecipitate E6 protein from HPV18-immortalized HeLa cells, confirming the interaction between PDZbody and HPV18 E6 in a cellular context.
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| 7. |
- Lindquist, Kajsa Ericson, et al.
(författare)
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Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:21, s. 34796-34810
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Tidskriftsartikel (refereegranskat)abstract
- Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics.
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| 8. |
- Nyqvist, Jenny, et al.
(författare)
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Metachronous and synchronous occurrence of 5 primary malignancies in a female patient between 1997 and 2013 : A case report with germline and somatic genetic analysis
- 2017
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Ingår i: Case Reports in Oncology. - : S. Karger AG. - 1662-6575. ; 10:3, s. 1006-1012
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Tidskriftsartikel (refereegranskat)abstract
- The number of patients with multiple primary malignancies has been increasing steadily in recent years. In the present study, we describe a unique case of an 81-year-old woman with 5 metachronous and synchronous primary malignant neoplasms. The patient was first diagnosed with an endometrium adenocarcinoma in 1997 and a colon adenocarcinoma in 2002. Eleven years after her colon surgery, in 2013, the patient presented with 3 other primary malignancies within a 4-month time span: An invasive malignant melanoma on the lower leg, an invasive mucinous breast carcinoma in the right breast, and a pleomorphic spindle cell sarcoma on the left upper arm. Subsequent routine medical checkups in 2013-2017 revealed no metastases of the primary malignancies. The patient mentioned a familial aggregation of malignant tumors, including 2 sisters with breast cancer and a brother with lung cancer. Interestingly, next-generation sequencing analysis of the patient's blood sample detected no mutations in the BRCA1, BRCA2, TP53, PTEN, CDH1, PALB2, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, STK11, BMPR1A, SMAD4, PTEN, POLE, POLD1, GREM1, and GALNT12 genes. Therefore, whole genome sequencing is warranted to identify cancer-related genetic alterations in this patient with quintuple primary malignancies.
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| 9. |
- Petersén, Anna, 1981-
(författare)
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Evaluations that matter in social work
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A great deal of evaluations are commissioned and conducted every year in social work, but research reports a lack of use of the evaluation results. This may depend on how the evaluations are conducted, but it may also depend on how social workers use evaluation results. The aim of this thesis is to explore and analyse evaluation practice in social work from an empirical, normative, and constructive perspective. The objectives are partly to increase the understanding of how we can produce relevant and useful knowledge for social work using evaluation results and partly, to give concrete suggestions on improvements on how to conduct evaluations. The empirical data has been organised as four cases, which are evaluations of temporary programmes in social work. The source materials are documents and interviews. The results show that findings from evaluations of temporary programmes are sparingly used in social work. Evaluations seem to have unclear intentions with less relevance for learning and improvement. In contrast, the evaluators themselves are using the data for new purposes. These empirical findings are elaborated further by using the knowledge form phronesis, which can be translated into practical wisdom. The overall conclusion is that social work is in need of knowledge that social workers find relevant and useful in practice. In order to meet these needs, researchers and evaluators must broaden their knowledge view and begin to include practical knowledge instead of solely relying on scientific knowledge when conducting evaluations. Finally, a new evaluation model is suggested. It is called phronesis-based evaluation and is argued to have great potential to address and include professionals’ praxis-based knowledge. It advocates a view that takes social work’s dynamic context into serious consideration and acknowledges values and power as important components of the evaluation process.
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