| 1. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 2. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 3. |
- Almby, Kristina E., et al.
(författare)
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Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
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Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
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| 4. |
- Barrdunge, Mats, 1956-
(författare)
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Upplysningens ljus i Norrland : Om fyra aktörer vid Härnösands gymnasium under 1700-talet
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this dissertation is to investigate the occurrence of Enlightenment ideas in the central Northern part of Sweden during the 18th century, focussing on a carefully chosen set of characters: one bishop and three senior lecturers at the gymnasium of Härnösand, in the province of Ångermanland. This dissertation uses a perspective of circulation of knowledge, inspired by the research field of history of knowledge. The methodological approach in this study is to use a complex thematic definition with eight different components of Enlightenment in the analysis of relevant texts and writings by selected characters, supplemented with a contextual perspective.A center for the ecclesiastical culture of learning in Norrland was Härnösand, and the gymnasium was Norrland´s only higher education institution, north of Gävle, for 200 years between 1650 and 1850. During the 18th century, three senior lecturers were employed there, each working for the dissemination of Enlightenment ideas, through both writing and practical action: Magnus Stridsberg (1696–1772), Nils Gissler (1715–1771) and Pehr Hellzén (1744–1811). At the same time as these, the diocese was governed by Bishop Olof Kiörning (1704–1778), who was also the Supervisor of the gymnasium. He was influenced by Enlightenment ideas and showed a strong interest in advanced agriculture and contributed to the church taking greater part in the social and economic development. The first lecturer, Magnus Stridsberg, created new methods in agriculture concerning soil mixing, manure production and grain nurseries, but has mainly been remembered for his threshing machine which came into general use in central Norrland during the second half of the 18th century. The next lecturer, Nils Gissler, was Norrland´s first provincial physician and introduced a scientific approach to practical medicine in the region. With the dissemination of knowledge and a great deal of personal commitment, he showed interest in mental illness and treated his patients in his own home. He laid the foundation for an infrastructure for public health care in the province. He was a member of the Swedish Academy of Sciences and wrote many scientific papers, and in modern times has received international scientific recognition for the discovery of the inverted barometer effect. The third lecturer, Pehr Hellzén, was a pre-industrial contractor in the sawmill and shipbuilding industry in central Norrland and founded the shipyard and shipping company Wifstavarf in 1798. Hellzén gave an important inaugural speech when the new gymnasium was built: Om uplysningens verkan på människors och samhällens sällhet (On the effect of Enlightenment on the happiness of people and societies), printed in Swedish 1794. He gave Härnösand a special role within the Enlightenment, described as a driving force behind the development of science, education and economic in the region.The Enlightenment that developed in Härnösand can be summarized as a Christian ‘utilism’ with clear Enlightenment traits such as reason, experience-based science, the dissemination of knowledge, humanity, social reforms, religious tolerance & religion of reason, and utility & virtue. It rested on an evangelical Lutheran foundation, it regarded the meaning of ‘utilism’ in a broader sense than just financial gain, and included central Enlightenment ideas.
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| 5. |
- Bock, David, 1976, et al.
(författare)
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Learning curve for robot-assisted laparoscopic radical prostatectomy in a large prospective multicentre study
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:3, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- Objective Differences in outcome after radical prostatectomy for prostate cancer can partly be explained by intersurgeon differences, where degree of experience is one important aspect. This study aims to define the learning curve of robot-assisted laparoscopic prostatectomy (RALP) regarding oncological and functional outcomes. Materials and methods Out of 4003 enrolled patients in the LAPPRO trial, 3583 met the inclusion criteria, of whom 885 were operated on by an open technique. In total, 2672 patients with clinically localized prostate cancer from seven Swedish centres were operated on by RALP and followed for 8 years (LAPPRO trial). Oncological outcomes were pathology-reported surgical margins and biochemical recurrence at 8 years. Functional outcomes included patient-reported urinary incontinence and erectile dysfunction at 3, 12 and 24 months. Experience was surgeon-reported experience before and during the study. The relationship between surgeon experience and functional outcomes and surgical margin status was analysed by mixed-effects logistic regression. Biochemical recurrence was analysed by Cox regression, with robust standard errors. Results The learning curve for positive surgical margins was relatively flat, with rates of 21% for surgeons who had performed 0-74 cases and 24% for surgeons with > 300 cases. Biochemical recurrence at 4 years was 11% (0-74 cases) and 13% (> 300 cases). Incontinence was stable over the learning curve, but erectile function improved at 2 years, from 38% (0-74 cases) to 53% (> 300 cases). Conclusions Analysis of the learning curve for surgeons performing RALP showed that erectile function improved with increasing number of procedures, which was not the case for oncological outcomes.
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| 6. |
- Boskovic, Andrea, et al.
(författare)
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Acoustic trapping in the undergraduate laboratory
- 2024
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Ingår i: American Journal of Physics. - : American Association of Physics Teachers (AAPT). - 0002-9505 .- 1943-2909. ; 92:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- Acoustic trapping is used in modern biophysics laboratories to study cell adhesion or aggregation, to sort particles, or to build model tissues. Here, we create an acoustic trapping setup in liquid for an undergraduate instructional laboratory that is low-cost, easy to build, and produces results in a 1-hour laboratory period. In this setup, we use a glass slide, cover slip, and double-sided tape to make the sample chamber. A piezo-electric transducer connected to a function generator serves as the acoustic source. We use this setup to measure the node spacing (millimeters) and the acoustic trap force (picoNewtons). We anticipate that the simplicity of the experimental setup, the tractability of the theoretical equations, and the richness of the research topics on the subject will lead to an undergraduate laboratory with many interesting student projects.
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| 7. |
- Carannante, Valentina, et al.
(författare)
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Generation of tumor spheroids in microwells to study NK cell cytotoxicity, infiltration and phenotype
- 2023
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Ingår i: Methods in Cell Biology. - : Elsevier BV. - 0091-679X. ; , s. 195-208
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The development of new immunotherapeutic drugs and combinatorial strategies requires the implementation of novel methods to test their efficacy in vitro. Here, we present a series of miniaturized in vitro assays to assess immune cell cytotoxic activity, infiltration, and phenotype in renal carcinoma spheroids with the use of a recently developed multichambered microwell chip. We provide protocols for tumor spheroid formation, NK cell culture, fluorescence labelling and imaging of live or fixed cells directly in the chip together with data analysis.
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| 8. |
- Carannante, Valentina, et al.
(författare)
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In vitro models to study natural killer cell dynamics in the tumor microenvironment
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Immunotherapy is revolutionizing cancer therapy. The rapid development of new immunotherapeutic strategies to treat solid tumors is posing new challenges for preclinical research, demanding novel in vitro methods to test treatments. Such methods should meet specific requirements, such as enabling the evaluation of immune cell responses like cytotoxicity or cytokine release, and infiltration into the tumor microenvironment using cancer models representative of the original disease. They should allow high-throughput and high-content analysis, to evaluate the efficacy of treatments and understand immune-evasion processes to facilitate development of new therapeutic targets. Ideally, they should be suitable for personalized immunotherapy testing, providing information for patient stratification. Consequently, the application of in vitro 3-dimensional (3D) cell culture models, such as tumor spheroids and organoids, is rapidly expanding in the immunotherapeutic field, coupled with the development of novel imaging-based techniques and -omic analysis. In this paper, we review the recent advances in the development of in vitro 3D platforms applied to natural killer (NK) cell-based cancer immunotherapy studies, highlighting the benefits and limitations of the current methods, and discuss new concepts and future directions of the field.
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| 9. |
- Carlsson-Wall, Martin, et al.
(författare)
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The role of management controls in managing heterogeneous interests during extreme situations: the Swedish migrant crisis in 2015
- 2021
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Ingår i: Qualitative Research in Accounting and Management. - : Emerald. - 1176-6093. ; 18:1, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThis paper aims to explore the role of management controls in managing heterogeneous interests during extreme situations.Design/methodology/approachThrough interviews and observations, the authors analyse the Swedish Migration Agency's management controls and study routines during the peak of the European Migrant Crisis.FindingsPrior to the crisis, the strategy used by the employees was to mediate between two interests (labelled legal security and empathy) to create a workable compromise. During the crisis, however, the authors observed filtering in the form of the previous hierarchical ordering of interests was further strengthened as the employees increasingly relied on just a single interest (the interest which they previously had deemed to be the most important) at the expense of the other interest. The findings suggest that behavioural and social controls helped such filtering; social controls helped certain employees to filter the empathy interest as more important during extreme situations and behavioural controls helped other employees to filter the legal security interest as more important. This help us explain why the authors observe less mediation between the two heterogeneous interests and rather a stricter dominance of one of the interests. The authors also illustrate how especially behavioural controls may become unsupportive of the operations during extreme situations as it consisted of rule-based standards, built to cope with "normal" situations. The heterogeneous interests affected the probability of actors, at times, ignoring behavioural controls when such controls were unsupportive. Actors whose day-to-day operations were mainly guided by the legal security interest remained tightly coupled to behavioural controls even when they felt that these controls were no longer useful. On the other hand, actors who were mainly guided by the empathy interest ignored behavioural controls when they felt that they were unsupportive.Research limitations/implicationsThe authors acknowledge that bias might arise from the reliance on retrospective views of past processes and events, which the authors primarily gathered through interviews.Practical implicationsThe authors highlight an important relationship between heterogeneous interests (i.e. legal security and empathy) and management controls during the crisis and how this relationship can lead actors to fundamentally different actions.Originality/valueThe two bodies of study on the role of management controls in managing heterogeneous interests and the role of management controls during the crisis have been largely unconnected and it is in this intersection that this study contributes.
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| 10. |
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