| 1. |
- Stenvall, Anna, et al.
(author)
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Relationships between uptake of [68Ga]Ga-DOTA-TATE and absorbed dose in [177Lu]Lu-DOTA-TATE therapy
- 2022
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 12:1
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Journal article (peer-reviewed)abstract
- Background: Somatostatin receptor 68Ga PET imaging is standard for evaluation of a patient’s suitability for 177Lu peptide receptor radionuclide therapy of neuroendocrine tumours (NETs). The 68Ga PET serves to ensure sufficient somatostatin receptor expression, commonly evaluated qualitatively. The aim of this study is to investigate the quantitative relationships between uptake in 68Ga PET and absorbed doses in 177Lu therapy. Method: Eighteen patients underwent [68Ga]Ga-DOTA-TATE PET imaging within 20 weeks prior to their first cycle of [177Lu]Lu-DOTA-TATE. Absorbed doses for therapy were estimated for tumours, kidney, spleen, and normal liver parenchyma using a hybrid SPECT/CT–planar method. Gallium-68 activity concentrations were retrieved from PET images and also used to calculate SUVs and normalized SUVs, using blood and tissue for normalization. The 68Ga activity concentrations per injected activity, SUVs, and normalized SUVs were compared with 177Lu activity concentrations 1 d post-injection and 177Lu absorbed doses. For tumours, for which there was a variable number per patient, both inter- and intra-patient correlations were analysed. Furthermore, the prediction of 177Lu tumour absorbed doses based on a combination of tumour-specific 68Ga activity concentrations and group-based estimates of the effective half-lives for grade 1 and 2 NETs was explored. Results: For normal organs, only spleen showed a significant correlation between the 68Ga activity concentration and 177Lu absorbed dose (r = 0.6). For tumours, significant, but moderate, correlations were obtained, with respect to both inter-patient (r = 0.7) and intra-patient (r = 0.45) analyses. The correlations to absorbed doses did not improve when using 68Ga SUVs or normalized SUVs. The relationship between activity uptakes for 68Ga PET and 177Lu SPECT was stronger, with correlation coefficients r = 0.8 for both inter- and intra-patient analyses. The 177Lu absorbed dose to tumour could be predicted from the 68Ga activity concentrations with a 95% coverage interval of − 65% to 248%. Conclusions: On a group level, a high uptake of [68Ga]Ga-DOTA-TATE is associated with high absorbed doses at 177Lu-DOTA-TATE therapy, but the relationship has a limited potential with respect to individual absorbed dose planning. Using SUV or SUV normalized to reference tissues do not improve correlations compared with using activity concentration per injected activity.
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| 2. |
- Uhlén, Mathias, et al.
(author)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Journal article (peer-reviewed)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 3. |
- Bokenstrand, Cecilia, 1961, et al.
(author)
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Alumnuppföljningar. Hur arbetar Göteborgs universitet med uppföljningar av tidigare studenter? En nulägesbeskrivning.
- 2009
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Reports (other academic/artistic)abstract
- Högskoleverket konstaterade 2004 i rapporten ”Uppföljning av studenter” att det genomförts en mängd alumnundersökningar vid Göteborgs universitet men att arbetet hade brister i systematik, samordning och återkoppling. Sedan Högskoleverket presenterade sin rapport för fem år sedan har arbetet med alumnuppföljningar vid Göteborgs universitet utvecklats i flera väsentliga avseenden. Inte minst har värdet av alumnuppföljningar fått en tydligare förankring i universitets styrdokument på både central- och fakultetsnivå. Vidare har en central stöd- och samordningsresurs tillkommit som bland annat genom uppbyggnad av den så kallade alumndatabasen skapat helt nya förutsättningar för direktkontakt och nätverksarbete med tidigare studenter. De senaste åren har också en rad ytterligare alumnuppföljningar genomförts, flera ämnes- eller programspecifika, några på fakultetsnivå och en universitetsövergripande. Men även om det gjorts framsteg i arbetet med alumnuppföljningar visar nulägesbeskrivningen att det fortsatt finns brister i arbetets systematik. Olika utbildningar/ämnen har kommit olika långt. Uppföljningarna varierar i fokus och omfång. I vissa fall sker undersökningarna regelbundet men mer vanligt är att de görs sporadiskt. Den stora merparten av alumnuppföljningarna i sammanställningen fokuserar på studenternas etablering på arbetsmarknaden. Ett flertal har också undersökt utbildningens relevans för arbetslivet och några har tittat på studenternas synpunkter på utbildningen. Enkätundersökningar i kombination med registerdata är det vanligaste tillvägagångssättet. Uppsala och Lunds universitets arbete med alumnuppföljningar har i olika sammanhang lyfts fram som goda exempel. Vid de här lärosätena görs alumnuppföljningar i samverkan mellan en central funktion och utbildningarna. I båda fallen arbetar man med en gemensam frågemall som vid utbildningsspecifika uppföljningar kompletteras med särskilt anpassade frågor. Undersökningarna fungerar som förändringsinstrument i syfte att skapa åtgärdsrelaterade informationsunderlag. Göteborgs universitet har inte utvecklat en liknande systematik vilket bland annat innebär att möjligheterna till jämförelser mellan undersökningar inom olika ämnen/ utbildningar och mellan undersökningar på olika nivåer är starkt begränsade. Utmärkande för arbetet med alumnuppföljningar vid Lunds och Uppsala universitet är också att det utgör en central del i de respektive lärosätenas kvalitetsutvecklingssystem. Alumnuppföljningarna vid Göteborgs universitet är inte på samma systematiska sätt integrerade i kvalitetsarbetet och variationerna inom universitet är stora när det gäller att använda alumnundersökningar som underlag för kvalitetsutveckling i utbildningen.
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| 4. |
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| 5. |
- Ceberg, Crister, et al.
(author)
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Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation.
- 2012
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In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:24, s. 8377-8391
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Journal article (peer-reviewed)abstract
- 75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.
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| 6. |
- Karlsson, Åsa, 1972-
(author)
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Team-based home rehabilitation after hip fracture in older adults : effects, experiences and impact of dementia
- 2021
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Doctoral thesis (other academic/artistic)abstract
- BACKGROUND: For an older adult a hip fracture may be a traumatic and life-changing event and has shown to be associated with reduced health-related quality of life, disability and increased mortality. Previous rehabilitation studies have often excluded older adults with cognitive impairment and those living in residential care facilities, groups with an additional risk of poor outcome. Moreover, there are few randomized controlled trials that have evaluated interdisciplinary home rehabilitation after hip fracture. These studies did not include older adults with severe cognitive impairment or dementia, those with serious medical conditions, or those living in residential care.OBJECTIVE: The aim of the thesis was to investigate the effects of early discharge followed by geriatric interdisciplinary home rehabilitation (GIHR) for older adults with hip fracture, and specifically among those with dementia, compared to in-hospital geriatric care according to a multifactorial rehabilitation program. An additional aim was to explore how older adults experienced their rehabilitation and recovery during the year following the fracture.METHODS: The thesis evaluated a randomized controlled trial that included 205 participants with hip fracture, 70 years or older, living in ordinary housing or residential care facilities. In hospital, both the GIHR and control groups received care and rehabilitation according to a multifactorial rehabilitation program, but with the aim of early discharge for the GIHR group. The individually designed GIHR intervention focused on walking ability indoors and outdoors, independence in activities of daily living (ADL), and multifactorial fall prevention during a maximum period of 10 weeks. Participants were assessed in-hospital and at 3- and 12-month follow-up visits. Independence in walking and use of walking aids was assessed via an interview along with gait speed tests. Independence in ADL was measured using the Barthel ADL Index, and the ADL Staircase including the Katz ADL Index, and hospital length of stay (LOS) was recorded from medical charts. The effects of GIHR intervention among participants with dementia were investigated in a post hoc subgroup analysis where additional outcomes were falls, mortality and readmissions between discharge and 12 months. Individual interviews were conducted with 20 selected participants just after the 12-month follow-up. Data were analysed using qualitative content analysis.RESULTS: The postoperative hospital LOS was significantly reduced by a median of six days in the GIHR group compared to the control group, although not significantly reduced in the GIHR group for participants with dementia. Binary logistic regression analyses revealed no significant differences between the GIHR and control groups regarding independent walking ability, the ability to walk without a walking device, or independence in ADL at 3 and 12 months. Gait speed was comparable between the two groups at 3 and 12 months. At 12 months, 56% in the GIHR group and 58% in the control group had recovered their prefracture walking ability, and 41% vs. 42% in GIHR and control groups, respectively, had regained their prefracture Barthel ADL Index score. Interaction analyses showed that the GIHR group vs. the control group had comparable effects on walking ability and ADL at 3 and 12 months, and on falls and mortality between discharge and 12 months, regardless of whether the participants had dementia or not (P≥0.05 for all). The number of readmissions and hospital days after discharge was comparable between GIHR and control groups for participants with dementia. Overall, dementia was associated with significantly impaired walking ability and greater dependence in ADL at 3 and 12 months and with increased risk of falling and increased mortality between discharge and 12 months compared to participants without dementia. The interviews revealed that access to rehabilitation, provided by skilled staff, and support from others were important for participants’ well-being and recovery. Participants experienced a fundamental change in their self-image after the fracture, and faced a number of difficulties, but strove for independence and used adaptive strategies to find contentment in their lives.CONCLUSIONS: In older adults with hip fracture, early discharge followed by interdisciplinary home rehabilitation significantly reduced postoperative hospital LOS. Functional recovery during the year following the fracture was nevertheless comparable to in-hospital geriatric care according to a multifactorial rehabilitation program. The GIHR intervention seems to be appropriate also for older adults with dementia since the effects were not different in this subgroup, except for postoperative hospital LOS, which was not significantly reduced in the GIHR group for participants with dementia. Further studies with larger samples are needed to validate these results. Overall, dementia was associated with a substantial negative impact on the outcomes. According to participants’ experiences, receiving rehabilitation and support after the hip fracture seems crucial for successful recovery. Negative psychological reactions were common, suggesting that future interventions should consider both physical and psychological aspects. Different rehabilitation alternatives were appreciated by the participants. Rehabilitation should thus be customised to suit wishes and needs of older adults and may accordingly be carried out in different settings, where rehabilitation in the home can be one suitable alternative. The findings of this thesis indicate that geriatric interdisciplinary home rehabilitation after hip fracture can be an alternative and a complement to in-hospital care and rehabilitation for older adults with and without dementia.
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| 7. |
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| 8. |
- Sarkadi, Anna, Professor, 1974-, et al.
(author)
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Teaching Recovery Techniques : evaluation of a group intervention for unaccompanied refugee minors with symptoms of PTSD in Sweden
- 2018
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In: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:4, s. 467-479
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Journal article (peer-reviewed)abstract
- In 2015, a total of 35,369 unaccompanied refugee minors (URMs) sought asylum in Sweden. In a previous study of 208 URMs, we found that 76% screened positive for PTSD. This study aimed to (1) evaluate the indicated prevention program Teaching Recovery Techniques (TRT) in a community setting and describe the program's effects on symptoms of PTSD and depression in URMs; and (2) examine participants' experiences of the program. The study included 10 groups. Methods for evaluation included the Children's Revised Impact of Event Scale (CRIES-8) and the Montgomery–Åsberg Depression Rating Scale Self-report (MADRS-S) at baseline and at post-intervention. Qualitative interviews were conducted with 22 participating URMs to elicit their experiences. Pre- and post-measures were available for 46 participants. At baseline, 83% of the participants reported moderate or severe depression and 48% suicidal ideation or plans. Although more than half (62%) of the participants reported negative life events during the study period, both PTSD (CRIES-8) and depression (MADRS-S) symptoms decreased significantly after the intervention (p = 0.017, 95% CI − 5.55; − 0.58; and p < 0.001, 95% CI − 8.94; − 2.88, respectively). The qualitative content analysis resulted in six overall categories: social support, normalisation, valuable tools, comprehensibility, manageability, and meaningfulness when the youth described their experiences of the program, well reflecting TRT's program theory. Overall, results indicate that TRT, delivered in a community setting, is a promising indicated preventive intervention for URMs with PTSD symptoms. This successful evaluation should be followed up with a controlled study.
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| 9. |
- Stenvall, Anna, et al.
(author)
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A small-scale anatomical dosimetry model of the liver.
- 2014
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In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 59:13, s. 3353-3371
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Journal article (peer-reviewed)abstract
- Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and (125)I, (90)Y, (211)At, (99m)Tc, (111)In, (177)Lu, (131)I and (18)F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons ((125)I) or high-LET alpha particles ((211)At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.
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| 10. |
- Stenvall, Anna, et al.
(author)
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Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3
- 2020
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 10:1
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Journal article (peer-reviewed)abstract
- Background: It is well known that a severe cell injury after exposure to ionizing radiation is the induction of DNA double-strand breaks (DSBs). After exposure, an early response to DSBs is the phosphorylation of the histone H2AX molecule regions adjacent to the DSBs, referred to as γ-H2AX foci. The γ-H2AX assay after external exposure is a good tool for investigating the link between the absorbed dose and biological effect. However, less is known about DNA DSBs and γ-H2AX foci within the tissue microarchitecture after internal irradiation from radiopharmaceuticals. Therefore, in this study, we aimed to develop and validate a quantitative ex vivo model using γ-H2AX immunofluorescence staining and confocal laser scanning microscopy (CLSM) to investigate its applicability in nuclear medicine dosimetry research. Liver and testis were selected as the organs to study after intravenous administration of 111InCl3. Results: In this study, we developed and validated a method that combines ex vivo γ-H2AX foci labeling of tissue sections with in vivo systemically irradiated mouse testis and liver tissues. The method includes CLSM imaging for intracellular cell-specific γ-H2AX foci detection and quantification and absorbed dose calculations. After exposure to ionizing radiation from 111InCl3, both hepatocytes and non-hepatocytes within the liver showed an absorbed dose-dependent elevation of γ-H2AX foci, whereas no such correlation was seen for the testis tissue. Conclusion: It is possible to detect and quantify the radiation-induced γ-H2AX foci within the tissues of organs at risk after internal irradiation. We conclude that our method developed is an appropriate tool to study dose–response relationships in animal organs and human tissue biopsies after internal exposure to radiation.
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