| 1. |
- Israelsson, Charlotte, et al.
(författare)
-
Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders
- 2010
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 31:5, s. 852-863
-
Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) in the mouse results in the rapid appearance of scattered clusters of cells expressing the chemokine Cxcl10 in cortical and subcortical areas. To extend the observation of this unique pattern, we used neuropathological mouse models using quantitative reverse transcriptase-polymerase chain reaction, gene array analysis, in-situ hybridization and flow cytometry. As for TBI, cell clusters of 150–200 μm expressing Cxcl10 characterize the cerebral cortex of mice carrying a transgene encoding the Swedish mutation of amyloid precursor protein, a model of amyloid Alzheimer pathology. The same pattern was found in experimental autoimmune encephalomyelitis in mice modelling multiple sclerosis. In contrast, mice carrying a SOD1G93A mutant mimicking amyotrophic lateral sclerosis pathology lacked such cell clusters in the cerebral cortex, whereas clusters appeared in the brainstem and spinal cord. Mice homozygous for a null mutation of the Cxcl10 gene did not show detectable levels of Cxcl10 transcript after TBI, confirming the quantitative reverse transcriptase-polymerase chain reaction and in-situ hybridization signals. Moreover, unbiased microarray expression analysis showed that Cxcl10 was among 112 transcripts in the neocortex upregulated at least threefold in both TBI and ageing TgSwe mice, many of them involved in inflammation. The identity of the Cxcl10+ cells remains unclear but flow cytometry showed increased numbers of activated microglia/macrophages as well as myeloid dendritic cells in the TBI and experimental autoimmune encephalomyelitis models. It is concluded that the Cxcl10+ cells appear in the inflamed central nervous system and may represent a novel population of cells that it may be possible to target pharmacologically in a broad range of neurodegenerative conditions.
|
|
| 2. |
|
|
| 3. |
- D'souza, Melroy A., et al.
(författare)
-
The clinicopathological spectrum and management of intraductal papillary mucinous neoplasm of the bile duct (IPMN-B)
- 2013
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 48:4, s. 473-479
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intraductal papillary mucinous neoplasm of the bile duct (IPMN-B) is a rare but increasingly diagnosed clinical entity. Typical cholangioscopic findings usually include intraductal protruding papillary tumors that secrete mucus.METHODS: Clinical, radiological and histopathological data of seven consecutive patients who were found to have IPMN-B were analyzed.RESULTS: Six of the seven patients presented with obstructive jaundice/cholangitis as the presenting complaint. ERCP and other imaging were equivocal in five of these patients and peroral cholangioscopy (POCS, single-operator cholangioscopy system) was performed. This revealed mucin-producing intraductal tumors with numerous frond-like papillary projections; a macroscopic appearance consistent with IPMN-B. Preoperative biopsy revealed adenoma, with low-grade dysplasia in two patients and high-grade dysplasia in three. Three patients underwent Whipple resection; one underwent total pancreatectomy with left hepatectomy, one patient a pancreas preserving duodenectomy with common bile duct reimplantation and one patient an extended right hepatectomy. These patients were found to have IPMN-B with adenomatous changes with varying grades of dysplasia and even cholangiocarcinoma on final histopathology. One patient first underwent endoscopic papillectomy and on follow-up was found to have cholangiocarcinoma with metastases to the liver.CONCLUSION: POCS can be a key diagnostic investigation in the evaluation of patients with papillary tumors of the bile duct. IPMN-B has a heterogenous pathology and varying grades of dysplasia and even carcinoma may exist in the same patient. Surgical management should be radical and based on tumor extent.
|
|
| 4. |
- Fornell, Jan, et al.
(författare)
-
Flapless, CBCT-guided osteotome sinus floor elevation with simultaneous implant installation. I: radiographic examination and surgical technique. A prospective 1-year follow-up.
- 2012
-
Ingår i: Clinical oral implants research. - : Wiley. - 1600-0501 .- 0905-7161. ; 23:1, s. 28-34
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable with those placed in non-augmented sites. Flapless implant surgery can minimize postoperative morbidity, alveolar bone resorption and crestal bone loss. The use of cone beam computerized tomography (CBCT) provides 3D presentations with reduced dose exposure. Objectives: To evaluate a flapless, CBCT-guided transalveolar sinus floor elevation technique with simultaneous implant installation. Material and methods: Fourteen consecutive patients in need of maxillary sinus floor augmentation were enrolled in this study. Preoperative CBCT with a titanium screwpost as an indicator at the intended implant position was used to visually guide the flapless surgical procedure. Twenty one implants all with a length of 10mm and a diameter of 4.1 and 4.8mm were inserted and followed clinically and with CBCT for 3, 6 and 12 months postoperatively. Intraoral radiographs were taken for comparison. All patients were provided with permanent prosthetic constructions 8-12 weeks after implant surgery. Results: Ten (47.6%) implants were inserted in residual bone of 2.6-4.9mm and 11 (52.3%) implants were inserted in residual bone of 5-8.9mm. No implants were lost after surgery and follow-up. There was no marginal bone loss during the follow-up verified by CBCT. The implants penetrated on average 4.4mm (SD 2.1mm) into the sinus cavity and the mean bone gain was 3mm (SD 2.1mm). Conclusion: Flapless transalveolar sinus lift procedures visually guided by preoperative CBCT can successfully be used to enable placement, successful healing and loading of one to three implants in residual bone height of 2.6-8.9mm. There was no marginal bone loss during the 3-12 months follow-up. To cite this article: Fornell J, Johansson L-Å, Bolin A, Isaksson S, Sennerby L. Flapless, CBCT-guided osteotome sinus floor elevation with simultaneous implant installation. I: radiographic examination and surgical technique. A prospective 1-year follow-up. Clin. Oral Impl. Res. xx, 2011; 000-000. doi: 10.1111/j.1600-0501.2010.02151.x.
|
|
| 5. |
- Gilg, Stefan, et al.
(författare)
-
The Molecular Adsorbent Recirculating System in Posthepatectomy Liver Failure : Results From a Prospective Phase I Study
- 2018
-
Ingår i: HEPATOLOGY COMMUNICATIONS. - : JOHN WILEY & SONS LTD. - 2471-254X. ; 2:4, s. 445-454
-
Tidskriftsartikel (refereegranskat)abstract
- Posthepatectomy liver failure (PHLF) represents the single most important cause of postoperative mortality after major liver resection, yet no effective treatment option is available. Extracorporeal liver support devices might be helpful, but systematic studies are lacking. Accordingly, we aimed to assess the safety and feasibility of the Molecular Adsorbent Recirculating System (MARS) in patients with PHLF. Between December 2012 and May 2015, a total of 206 patients underwent major or extended hepatectomy, and 10 consecutive patients with PHLF (according to the Balzan 50: 50 criteria) were enrolled into the study. MARS treatment was initiated on postoperative day 5-7, and five to seven consecutive treatment sessions were completed for each patient. In total, 59 MARS cycles were implemented, and MARS was initiated and completed without major complications in any patient. However, 1 patient developed an immense asymptomatic hyperbilirubinemia (without encephalopathy), 1 had repeated clotting problems in the MARS filter, and 2 patients experienced access problems with the central venous line. Otherwise, no adverse events were observed. In 9 patients, the bilirubin level and international normalized ratio decreased significantly (P < 0.05) during MARS treatment. The 60- and 90-day mortality was 0% and 10%, respectively. Among the 9 survivors, 4 still had liver dysfunction at 90 days postoperatively. Five patients were alive 1 year postoperatively without any signs of liver dysfunction or disease recurrence. Conclusion: The use of MARS in PHLF is feasible and safe and improves liver function in patients with PHLF. In the present study, 60- and 90-day mortality rates were unexpectedly low compared to a historical control group. The impact of MARS treatment on mortality in PHLF should be further evaluated in a randomized controlled clinical trial.
|
|
| 6. |
- Hirsch, Jan-Mikael, et al.
(författare)
-
A clinical evaluation of the Zygoma fixture: one year of follow-up at 16 clinics.
- 2004
-
Ingår i: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 62:9 Suppl 2, s. 22-9
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate treatment outcome with Zygoma fixtures (Nobel Biocare, Göteborg, Sweden) with regard to fixture survival, patient satisfaction, and function of prosthesis replacement. MATERIALS AND METHODS: The treatment outcome of 76 patients treated with 145 Zygoma fixtures at 16 centers was evaluated. Patient's and dentist's evaluations of the functional and aesthetic outcome of the treatment were assessed at delivery of prosthesis and at the 1-year follow-up visit. At the 1-year follow-up visit, the status of the peri-implant mucosa around the abutments and the amount of plaque were registered. RESULTS: Sixty-six of the 76 patients, with 124 Zygoma fixtures supporting the prosthetic restorations, were evaluated at the 1-year follow-up. The overall survival rate for the Zygoma fixtures was 97.9% after 1-year of follow-up. Eighty percent of the patients were fully satisfied with both aesthetic and functional outcome at the time of prosthetic insertion and at the 1-year follow-up. All reported data from the dentists, with the exception of one restoration with several abutment screw loosenings, scored from acceptable to excellent for the aesthetic and functional outcome of the treatment. The status of peri-implant mucosa was recorded as normal in approximately 60% of the sites. Plaque, when present, was more often detected on the palatal surfaces compared with the buccal surfaces. CONCLUSION: This 1-year follow-up of Zygoma fixtures has shown good results with an acceptable number of minor complications and a majority of satisfied patients.
|
|
| 7. |
- Johansson, Lars-Åke, 1950, et al.
(författare)
-
Bone Regeneration Using a Hollow Hydroxyapatite Space-Maintaining Device for Maxillary Sinus Floor Augmentation – A Clinical Pilot Study
- 2012
-
Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 14:4, s. 575-584
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: The mere lifting of the maxillary sinus membrane by implants protruding into the sinus cavity allows the establishment of a void space for blood clot and new bone formation. Purpose: To evaluate bone formation by using a spherical, hollow, and perforated hydroxyapatite space-maintaining device (HSMD) in a two-stage sinus lift procedure where residual alveolar bone height was
|
|
| 8. |
|
|
| 9. |
- Kahnberg, Karl-Erik, 1941, et al.
(författare)
-
Clinical evaluation of the zygoma implant : 3-year follow-up at 16 clinics
- 2007
-
Ingår i: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 65:10, s. 2033-2038
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this clinical investigation was to evaluate the treatment outcome with zygoma implants with regard to implant survival, patient satisfaction, and function of prosthesis replacement after 3 years. Patients and Methods: The treatment outcome of 76 patients treated with 145 zygoma fixtures at 16 centers was evaluated with regard to implant survival. Status of peri-implant mucosa and amount of plaque were registered annually. Patients' and dentists' evaluations of the functional and esthetic outcome of the treatment were assessed at delivery of prosthesis and thereafter at each follow-up visit. Results: Sixty of 76 patients were followed for 3 years after prosthetic delivery. Five of 145 placed zygoma implants failed during the course of the study resulting in an overall implant survival rate of 96.3%. At the 3-year follow-up, 75% of the implants sites were registered with normal peri-implant mucosa and 68% with no visible plaque. The patients were fully satisfied with the esthetic and functional outcome of the treatment in 86% and 71%, respectively, at the 3-year follow-up visit. All reported data from dentists scored from acceptable to excellent. Conclusion: The multicenter study showed a high predictability of the zygoma implant-supported rehabilitation.
|
|
| 10. |
|
|
| 11. |
- Slotte, Christer, 1954, et al.
(författare)
-
Four-Millimeter Implants Supporting Fixed Partial Dental Prostheses in the Severely Resorbed Posterior Mandible: Two-Year Results.
- 2011
-
Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Reduced alveolar bone volume complicates implant dentistry. Purpose: In this prospective multicenter study, a new, 4-mm long Straumann SLActive implant (Ø 4.1mm) supporting a fixed dental prosthesis (FDP) in the severely resorbed posterior mandible was evaluated for two years. Material and Methods: Thirty-two patients (11 men, 21 women; mean age 64.1 years) participated. Ten to 12 weeks after single-stage surgery, a screw-retained FDP was attached to three or four 4-mm implants. Results and Discussion: One hundred implants were inserted. Three failed at surgery and four were lost before loading. Twenty-eight patients received FDPs (93 implants). Two patients were discontinued because of secondary exclusion criteria; therefore, 26 patients were followed up from baseline (BL). After 1 year, one patient insisted on removal of all implants and one patient died because of nonstudy-related complications. Twenty-four patients (87 implants) were eligible for examination 2 years post-loading. All implants were found to be stable [survival rate 95.7% (confidence interval, CI 88.8-98.3) after 1 year and 92.3% (CI 84.5-96.2) after 2 years]. The mean change from BL to 12 months was - 0.43mm (CI 0.31-0.59; p<.001) and from 12 to 24 months - 0.11mm (CI -0.01-0.23; p=.056). The survival rate is only slightly lower than in similar studies on 6 to 8.5mm implants. This may be related to high initial stability and effective use of the residual bone volume with high primary bone-to-implant contact in dense bone structures. The surgical handling of the tested implant was found to be similar to that of implants of common length. However, the preparation procedure must be done with great care to avoid overdrilling. Careful planning and design of the prosthetic construction is mandatory to prevent unfavorable occlusion and avoid harmful shear forces. Conclusion: This study showed that 4mm implants can support an FDP in severely resorbed posterior mandibles for at least 2 years and with healthy peri-implant conditions.
|
|
| 12. |
- Slotte, Christer, 1954, et al.
(författare)
-
Four-Millimeter-Long Posterior-Mandible Implants: 5-Year Outcomes of a Prospective Multicenter Study.
- 2015
-
Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 17:2
-
Tidskriftsartikel (refereegranskat)abstract
- There is lack of evidence on long-term success of short dental implants in reduced alveolar bone. Purpose In this prospective 5-year study, survival and marginal bone loss of 4-mm implants, which supported fixed dental prostheses (FDPs) in severely resorbed posterior mandibles, were evaluated. Material and Methods In 28 patients, evaluation of 86 osseointegrated 4-mm-long implants, which supported a 3- or a 4-unit FDP by crown splinting without the use of pontics or cantilevers, was performed over a 5-year period. Results Three subjects dropped out for non-study reasons: one subject had her three implants removed after 1 year and two subjects died (six implants). Five implants in three subjects were lost between 3 and 5 years. Twenty-four subjects and 71 implants were active at the 5-year follow-up (92.2% survival). After 1 year, significant (p<.001) mean (standard error of the mean [SEM]) 0.44-mm (0.05) marginal bone loss occurred. At 2, 3, and 5 years, mean (SEM) bone loss of 0.57mm (0.06), 0.55mm (0.07), and 0.53mm (0.08) occurred, respectively (no significant change after 1 year). At 5 years, average plaque levels were 13.3%; 69% of the implants were plaque free. On average, mucosal bleeding occurred at 8.1% of the implants. During 5 years, two subjects experienced uncomplicated bridge loosening. No other complications occurred during the study. Conclusion Four-millimeter implants can support FDPs in severely resorbed posterior mandibles for 5 years with healthy peri-implant conditions.
|
|
| 13. |
|
|
| 14. |
- Åberg, N David, 1970, et al.
(författare)
-
Growth hormone increases connexin-43 expression in the cerebral cortex and hypothalamus.
- 2000
-
Ingår i: Endocrinology. - 0013-7227. ; 141:10, s. 3879-86
-
Tidskriftsartikel (refereegranskat)abstract
- Several studies indicate that systemic GH influences various brain functions. Connexin-43 forms gap junctions that mediate intercellular communication and establish the astroglial syncytium. We investigated the effects of peripheral administration of bovine GH (bGH) and recombinant human insulin-like growth factor I (rhIGF-I) on the expression of connexin-43 in the rat brain. Hypophysectomized female Sprague Dawley rats were substituted with cortisol (400 microg/kg x day) and L-T4 (10 microg/kg x day) and treated with either bGH (1 mg/kg x day) or rhIGF-I (0.85 mg/kg x day) for 19 days. The abundance of connexin-43 messenger RNA (mRNA) and protein in the brainstem, cerebral cortex, hippocampus, and hypothalamus was quantified by means of ribonuclease protection assays and Western blots. Treatment with bGH increased the amounts of connexin-43 mRNA and protein in the cerebral cortex and hypothalamus. No changes were found in the brainstem or hippocampus. Infusion of rhIGF-I did not affect connexin-43 mRNA or protein levels in any of the brain regions studied. These results show that administration of bGH increases the abundance of cx43 in specific brain regions, suggesting that GH may influence gap junction formation and thereby intercellular communication in the brain.
|
|
| 15. |
- Adler, Jan-Olof, et al.
(författare)
-
The upgraded photon tagging facility at the MAX IV Laboratory
- 2013
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 715, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- A description is given of the upgraded photon tagging facility at the MAX IV Laboratory. Two magnetic spectrometers are used to momentum analyze post-bremsstrahlung electrons. The tagged photon range extends from 10 to 180 MeV with an energy resolution of about 300 keV. The system has been operated at rates up to 4 x 10(6) photons s(-1) MeV (-1). Different diagnostic tools are described as well as the experimental program.
|
|
| 16. |
- Almgren, Sara, 1979, et al.
(författare)
-
Gamma radiation doses to people living in Western Sweden.
- 2008
-
Ingår i: Journal of environmental radioactivity. - : Elsevier BV. - 0265-931X. ; 99:2, s. 394-403
-
Tidskriftsartikel (refereegranskat)abstract
- Indoor environments contribute to gamma radiation in the general population. The aims of the present study were to investigate average gamma radiation doses in a rural and an urban area of Sweden, compare indoor dose rates with personal exposure, and study the effects of building characteristics on radiation levels. Radiation was measured with thermoluminescence dosimeters (TLDs). Repeated measurements were performed with TLDs worn by participants (n=46) and placed in their dwellings. Personal dose rates were 0.092microSv/h (rural) and 0.096microSv/h (urban). The mean effective gamma dose rates in dwellings were 0.091microSv/h (rural) and 0.11microSv/h (urban), which are higher than the world average. Dose rates in apartments were higher than in detached houses and higher for concrete than wooden dwellings. Personal dose rates were strongly associated with dwelling dose rates (r(p)=0.68, p<0.01) and could be modelled. Within-participant variability was low.
|
|
| 17. |
- Almgren, Sara, 1979, et al.
(författare)
-
Measurements and comparisons of gamma radiation doses in a high and a low (137)Cs deposition area in Sweden.
- 2008
-
Ingår i: Journal of environmental radioactivity. - : Elsevier BV. - 0265-931X. ; 99:11, s. 1750-5
-
Tidskriftsartikel (refereegranskat)abstract
- Sweden is one of the countries affected by the Chernobyl fallout. The aim of the present study was to investigate the average radiation dose to people living in a high-deposition area (the parish of Hille) in Sweden for comparison with dose rates previously measured in a low-deposition area in western Sweden. Individual measurements (personal and dwelling dose rates) were performed using thermoluminescence dosimeters in 24 randomly chosen individuals. Dwelling and personal dose rates in Hille were 0.12 and 0.11 microSv/h, respectively. The dose rates in Hille were slightly higher than in western Sweden (difference for detached houses=0.024 microSv/h for personal and 0.030 microSv/h for dwelling dose rates), partly because of the higher (137)Cs deposition. In wooden houses, the difference was somewhat greater. Our results indicate a current contribution to personal gamma radiation in this area of about 0.2 mSv per year from the Chernobyl fallout.
|
|
| 18. |
- Alsiö, Johan, et al.
(författare)
-
Impact of nandrolone decanoate on gene expression in endocrine systems related to the adverse effects of anabolic androgenic steroids
- 2009
-
Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 105:5, s. 307-314
-
Tidskriftsartikel (refereegranskat)abstract
- Elite athletes, body builders and adolescents misuse anabolic-androgenic steroids (AAS) in order to increase muscle mass or to enhance physical endurance and braveness. The high doses misused are associated with numerous adverse effects. The purpose of this study was to evaluate the impact of chronic supratherapeutic AAS treatment on circulating hormones and gene expression in peripheral tissues related to such adverse effects. Quantitative real-time PCR was used to measure expression levels of in total 37 genes (including peptide hormones, cell membrane receptors, nuclear receptors, steroid synthesising enzymes and other enzymes) in the pituitary, testes, adrenals, adipose tissue, kidneys and liver of male Sprague-Dawley rats after 14-day administration of the AAS nandrolone decanoate, 3 or 15 mg/kg. Plasma glucose and levels of adrenocorticotropic hormone (ACTH), adiponectin, corticosterone, ghrelin, insulin and leptin were also measured. We found several expected effects on the hypothalamic-pituitary-gonadal axis, while the treatment also caused a number of other not previously identified changes in circulating factors and gene transcription levels such as the dose-dependent reduction of the beta(3)-adrenergic receptor in adipose tissue, reduction of both circulating and mRNA levels of adiponectin, up-regulation of both hydroxymethylglutaryl-CoA-reductase, the rate-limiting enzyme in de novo synthesis of cholesterol, and the receptor for ACTH in the adrenals. The results provide evidence for wide ranging effects of AAS on the hypothalamic-pituitary-adrenal axis, adipose tissue and substrates of the renal control of blood pressure.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Birgisson, Helgi, et al.
(författare)
-
Microsatellite instability and mutations in BRAF and KRAS are significant predictors of disseminated disease in colon cancer
- 2015
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Molecular alterations are well studied in colon cancer, however there is still need for an improved understanding of their prognostic impact. This study aims to characterize colon cancer with regard to KRAS, BRAF, and PIK3CA mutations, microsatellite instability (MSI), and average DNA copy number, in connection with tumour dissemination and recurrence in patients with colon cancer. Methods: Disease stage II-IV colon cancer patients (n = 121) were selected. KRAS, BRAF, and PIK3CA mutation status was assessed by pyrosequencing and MSI was determined by analysis of mononucleotide repeat markers. Genome-wide average DNA copy number and allelic imbalance was evaluated by SNP array analysis. Results: Patients with mutated KRAS were more likely to experience disease dissemination (OR 2.75; 95% CI 1.28-6.04), whereas the opposite was observed for patients with BRAF mutation (OR 0.34; 95% 0.14-0.81) or MSI (OR 0.24; 95% 0.09-0.64). Also in the subset of patients with stage II-III disease, both MSI (OR 0.29; 95% 0.10-0.86) and BRAF mutation (OR 0.32; 95% 0.16-0.91) were related to lower risk of distant recurrence. However, average DNA copy number and PIK3CA mutations were not associated with disease dissemination. Conclusions: The present study revealed that tumour dissemination is less likely to occur in colon cancer patients with MSI and BRAF mutation, whereas the presence of a KRAS mutation increases the likelihood of disseminated disease.
|
|
| 31. |
|
|
| 32. |
- Bradley, Karin, 1975-, et al.
(författare)
-
Hållbara staden fångad i ett postpolitiskt vakuum
- 2008
-
Ingår i: Arkitekten. - 0903-2347. ; :12
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Den "täta staden" framställs som enda vägen mot framtiden. Men den vägen är varken så okontroversiell eller opolitisk som det verkar, skriver Karin Bradley, Karolina Isaksson och Lars Orrskog vid KTH.
|
|
| 33. |
- Brittberg, Mats, 1953, et al.
(författare)
-
Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.
- 1994
-
Ingår i: The New England journal of medicine. - 0028-4793. ; 331:14, s. 889-95
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. METHODS. The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. RESULTS. Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and swelling in all patients. After three months, arthroscopy showed that the transplants were level with the surrounding tissue and spongy when probed, with visible borders. A second arthroscopic examination showed that in many instances the transplants had the same macroscopic appearance as they had earlier but were firmer when probed and similar in appearance to the surrounding cartilage. Two years after transplantation, 14 of the 16 patients with femoral condylar transplants had good-to-excellent results. Two patients required a second operation because of severe central wear in the transplants, with locking and pain. A mean of 36 months after transplantation, the results were excellent or good in two of the seven patients with patellar transplants, fair in three, and poor in two; two patients required a second operation because of severe chondromalacia. Biopsies showed that 11 of the 15 femoral transplants and 1 of the 7 patellar transplants had the appearance of hyaline cartilage. CONCLUSION. Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.
|
|
| 34. |
|
|
| 35. |
- Bugaeva, Elizaveta Y, et al.
(författare)
-
Structural features of the tmRNA-ribosome interaction
- 2009
-
Ingår i: RNA. - : RNA Society. - 1355-8382 .- 1469-9001. ; 15:12, s. 2312-2320
-
Tidskriftsartikel (refereegranskat)abstract
- Trans-translation is a process which switches the synthesis of a polypeptide chain encoded by a nonstop messenger RNA to the mRNA-like domain of a transfer-messenger RNA (tmRNA). It is used in bacterial cells for rescuing the ribosomes arrested during translation of damaged mRNA and directing this mRNA and the product polypeptide for degradation. The molecular basis of this process is not well understood. Earlier, we developed an approach that allowed isolation of tmRNA-ribosomal complexes arrested at a desired step of tmRNA passage through the ribosome. We have here exploited it to examine the tmRNA structure using chemical probing and cryo-electron microscopy tomography. Computer modeling has been used to develop a model for spatial organization of the tmRNA inside the ribosome at different stages of trans-translation.
|
|
| 36. |
- Börjesson, Per Ola, et al.
(författare)
-
A low-complexity PAR-reduction method for DMT-VDSL
- 1999
-
Ingår i: Proceedings of the 5th International Symposium on Digital Signal Processing for Communication Systems. ; , s. 164-169
-
Konferensbidrag (refereegranskat)abstract
- DMT-VDSL signals have a high peak-to-average power ratio (PAR). In the transmitters, the PAR governs the necessary resolution of the digital-to-analog converter (DAC) and is an important factor for the power consumption of the line-driver. Aiming at implementation in a specific system, we propose a low complexity PAR-reduction method based on the iterative algorithm derived in [5, 20, 24, 25]. We maintain good performance while stressing a straigthforward and low-complex implementation. Key elements of the method are: low latency; no loss in data rate; precalculated and stored peak-cancellation waveform; and bit-shifts (multiplication with powers of two) replacing the scaling of the waveform. Computer simulations show that, for a DMT frame length of 4096 samples and a frame clip rate of 10-4, the PAR can be reduced about 1.5 to 2.0 dB, depending on the number of peaks cancelled. When multiplication is replaced by bit-shifts, the reduction is still 1.5-1.7 dB.
|
|
| 37. |
- Cabrita, Rita, et al.
(författare)
-
Tertiary lymphoid structures improve immunotherapy and survival in melanoma
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7791, s. 561-565
-
Tidskriftsartikel (refereegranskat)abstract
- Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
|
|
| 38. |
- Cabrita, Rita, et al.
(författare)
-
Tertiary lymphoid structures improve immunotherapy and survival in melanoma.
- 2020
-
Ingår i: Nature. - : Nature Publishing Group. - 1476-4687 .- 0028-0836. ; 577:7791, s. 561-565
-
Tidskriftsartikel (refereegranskat)abstract
- Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
|
|
| 39. |
- Chevul, Stefan, et al.
(författare)
-
Measurements of Application-Perceived Throughput in DAB, GPRS, UMTS and WLAN Environments
- 2005
-
Konferensbidrag (refereegranskat)abstract
- Communication services are expected to deliver the desired information in a timely manner without challenging the user’s patience. The corresponding offers by networks are reflected in user- or applications-perceived throughput, which is measured end-to-end for different mobile and wireless networks, namely Digital Audio Broadcast (DAB), General Packet Radio Service (GPRS), Universal Mobile Telecommunication Systems (UMTS), and Wireless Local Area Networks (WLAN). The measurements are based on passive monitoring of throughput statistics for active test traffic and reveal amongst others different kinds of changes of traffic burstiness induced by mobile up- and downlinks and by buffering, respectively. The results will be used for seamless communication, i.e. automatic network selection within the project PIITSA (Personal Information for Intelligent Transport Systems through Seamless communications and Autonomous decisions) aiming at maintaining user-perceived performance and security at the desired levels while keeping communication cost as small as possible.
|
|
| 40. |
- Darmanis, Spyros, et al.
(författare)
-
Multiplexed solid-phase proximity ligation assays: Highly specific and parallel protein measurements with DNA sequencing readout
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Identification and validation of protein biomarkers is a very important step towards the understanding of the underlying mechanisms of disease, early diagnosis and efficient patient treatment. To carry out this task, methods are needed that would allow us to mine the proteome with sufficient sensitivity and specificity in large sets of samples. We present herein the development of a Multiplexed Proximity Ligation Assay (MultiPLAy), to facilitate efficient protein profiling in a parallel, sensitive and specific manner. We showed that for the simultaneous analysis of 35 proteins MultiPLAy exhibited an improved sensitivity over conventional sandwich assays as well as a smaller susceptibility to background signal increase in the transition from singleplex to multiplex. We used MultiPLAy to identify putative biomarkers in two separate sample cohorts of colorectal cancer (CRC) and cardiovascular disease (CVD) and with the use a novel multivariate analysis approach were able to identify new, as well as already known diagnostic biomarkers. Furthermore we were able to combine MultiPLAy with the use of next-generation sequencing allowing for the first time digital recording of protein profiles in blood. We demonstrated good reproducibility of MultiPLAy coupled to next-generation sequencing, as well as a satisfactory correlation to standard real-time PCR readout. We conclude that MultiPLAy has great potential as a basis for highly multiplexed protein detection assays that can be utilized for the identification of large numbers of proteins or protein variants. This will allow extensive validation of protein expression patterns in biobanked samples and in prospective studies, and can provide a much-needed platform for efficient validation of diagnostic markers for clinical use.
|
|
| 41. |
- Edlund, Karolina, et al.
(författare)
-
CD99 is a novel prognostic stromal marker in non-small cell lung cancer
- 2012
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:10, s. 2264-2273
-
Tidskriftsartikel (refereegranskat)abstract
- The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumourstroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.
|
|
| 42. |
- Eisen, Olaf, et al.
(författare)
-
Ground-based measurements of spatial and temporal variability of snow accumulation in East Antarctica
- 2008
-
Ingår i: Reviews of Geophysics. - 8755-1209. ; 46, s. 1-39
-
Tidskriftsartikel (refereegranskat)abstract
- The East Antarctic Ice Sheet is the largest, highest, coldest, driest, and windiest ice sheet on Earth. Understanding of the surface mass balance (SMB) of Antarctica is necessary to determine the present state of the ice sheet, to make predictions of its potential contribution to sea level rise, and to determine its past history for paleoclimatic reconstructions. However, SMB values are poorly known because of logistic constraints in extreme polar environments, and they represent one of the biggest challenges of Antarctic science. Snow accumulation is the most important parameter for the SMB of ice sheets. SMB varies on a number of scales, from small-scale features (sastrugi) to ice-sheet-scale SMB patterns determined mainly by temperature, elevation, distance from the coast, and wind-driven processes. In situ measurements of SMB are performed at single points by stakes, ultrasonic sounders, snow pits, and firn and ice cores and laterally by continuous measurements using ground-penetrating radar. SMB for large regions can only be achieved practically by using remote sensing and/or numerical climate modeling. However, these techniques rely on ground truthing to improve the resolution and accuracy. The separation of spatial and temporal variations of SMB in transient regimes is necessary for accurate interpretation of ice core records. In this review we provide an overview of the various measurement techniques, related difficulties, and limitations of data interpretation; describe spatial characteristics of East Antarctic SMB and issues related to the spatial and temporal representativity of measurements; and provide recommendations on how to perform in situ measurements.
|
|
| 43. |
- Enochsson, Lars, et al.
(författare)
-
Bile duct obstruction is associated with early postoperative upregulation of liver uncoupling protein-2 and reduced circulating glucose concentration in the rat
- 2010
-
Ingår i: Nutrition. - : Elsevier BV. - 1873-1244 .- 0899-9007. ; 26:4, s. 405-410
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate whether upregulation of liver and muscle uncoupling protein 2 (UCP-2) is an acute phenomenon in obstructive jaundice and associated with secondary metabolic effects. Methods: Male Sprague-Dawley rats were divided into four groups bile duct ligated (BDL) and sham-operated pair-fed (PF), ad libitum fed (AL), and controls BDL. PF. and AL rats were further divided into subgroups according to the interval postoperatively when they were reanesthetized and sampled for tissue and blood 2, 4, and 8 d, respectively Bilirubin, liver enzymes. glucose, free fatty acids, and insulin in blood plasma were analyzed Liver and muscle tissue were sampled for UCP-2 and adenosine triphosphate analysis. Results: The BDL rats showed an increase of the liver UCP-2 expression compared with PF and AL rats (P < 0 05) 4 d postoperatively. Liver adenosine triphosphate in BDL rats showed a decrease compared with sham-operated controls at all intervals < 0 05) Plasma glucose concentration in BDL rats was decreased compared with the other groups. Free fatty acids showed an initial increase 2 d postoperatively compared with sham-operated controls and PF and AL rats (P < 0 05) at the corresponding time point Conclusion: Obstructive jaundice is associated with an early upregulation of liver UCP-2. reduced liver adenosine triphosphate content, and decreased plasma glucose concentration, supporting the hypothesis that obstructive Jaundice results in impaired energy homeostasis in the liver. which might cause decreased glucose output and hypoglycemia as a consequence (C) 2010 Elsevier Inc. All flats reserved
|
|
| 44. |
- Farman, Helen H., 1983, et al.
(författare)
-
Female Mice Lacking Estrogen Receptor-alpha in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass
- 2016
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 157:8, s. 3242-3252
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor(ER)alpha. Central ER alpha exerts an inhibitory role on bone mass. ER alpha is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ER alpha in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ER alpha expression specifically in POMC neurons (POMC-ER alpha(-/-)). Female POMC-ER alpha(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 mu g/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ER alpha(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+ 126 +/- 34%, P < .01) and mechanical strength (+ 193 +/- 38%, P <.01). To test whether ER alpha in VMN is involved in the regulation of bone mass, ER alpha was silenced using an adeno-associated viral vector. Silencing of ER alpha in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ER alpha in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ER alpha activity in hypothalamic POMC neuronsin ARC and stimulatory peripheral ER alpha-mediated effects in bone determines cortical bone mass in female mice.
|
|
| 45. |
- Fischer Grönlund, Catarina, 1962-, et al.
(författare)
-
Development, validity and reliability testing the Swedish Ethical Climate Questionnaire
- 2019
-
Ingår i: Nursing Ethics. - : SAGE Publications. - 0969-7330 .- 1477-0989. ; 26:7-8, s. 2482-2493
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: An ethical climate has been described as a working climate embracing shared perceptions about morally correct behaviour concerning ethical issues. Various ethical climate questionnaires have been developed and validated for different contexts, but no questionnaire has been found concerning the ethical climate from an inter-professional perspective in a healthcare context. The Swedish Ethical Climate Questionnaire, based on Habermas' four requirements for a democratic dialogue, attempts to assess and measure the ethical climate at various inter-professional workplaces. This study aimed to present the construction of and to test the psychometric properties of the Swedish Ethical Climate Questionnaire.METHOD:: An expert group of six researchers, skilled in ethics, evaluated the content validity. The questionnaire was tested among 355 healthcare workers at three hospitals in Sweden. A parallel analysis (PA), an exploratory factor analysis and confirmatory factor analysis were performed.ETHICAL CONSIDERATIONS:: The participants included in the psychometric analysis were informed about the study, asked to participate in person and informed that they could withdraw at any time without giving any reason. They were also assured of confidentiality in the reporting of the results.FINDINGS:: The parallel analysis (PA) recommended one factor as a solution. The initial exploratory factor analysis with a four-factor solution showed low concordance with a four-factor model. Cronbach's alpha varied from 0.75 to 0.82; however, since two factors only consisted of one item, alpha could not be reported. Cronbach's alpha for the entire scale showed good homogeneity (α = 0.86). A confirmatory factory analysis was carried out based on the four requirements and showed a goodness-of-fit after deleting two items. After deletion of these items, Cronbach's alpha was 0.82.DISCUSSION:: Based on the exploratory factor analysis, we suggest that the scale should be treated as a one-factor model. The result indicates that the instrument is unidimensional and assesses ethical climate as a whole.CONCLUSION:: After testing the Swedish Ethical Climate Questionnaire, we found support for the validity and reliability of the instrument. We found the 10-item version of Swedish Ethical Climate Questionnaire satisfactory. However, we found no support for measuring different dimensions and, therefore, this instrument should be seen as assessing ethical climate as of whole.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Garkavij, Michael, et al.
(författare)
-
Extracorporeal immunoadsorption from whole blood based on the avidin-biotin concept. Evaluation of a new method
- 1996
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 35:3, s. 309-312
-
Tidskriftsartikel (refereegranskat)abstract
- This study of 36 rats with rat colon adenocarcinoma transplants was carried out to investigate the efficacy of a new method of whole blood immunoadsorption (WBIA) in removing biotinylated monoclonal antibodies (MAbs) directly from unseparated blood, in order to increase 'the tumor/normal-tissue uptake ratio', as compared with extracorporeal immunoadsorption (ECIA) of antibodies from plasma. Compared with the ECIA system, the overall volume of the WBIA system (comprising only a pump, an adsorption column, a drop-chamber and tubings) was less (3.6 vs. 6.2 ml), and procedure duration 2 h less. The 17 rats undergoing the WBIA procedure, started 12 h after i.v. injection of 4.0-4.5 MBq 125I-BR96-biotin, manifested neither hemolysis nor any other complication; no signs of organ edema were found at dissection; whole body and blood radioactivity values were reduced by 51% and 89.5%, respectively. The WBIA method was as effective as ECIA, but technically simpler, safer and more reliable.
|
|
| 49. |
- Grassi, Lorenzo, et al.
(författare)
-
3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort
- 2023
-
Ingår i: Journal of Bone and Mineral Research. - : John Wiley & Sons. - 0884-0431 .- 1523-4681. ; 38:9, s. 1258-1267
-
Tidskriftsartikel (refereegranskat)abstract
- Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed amethod to reconstruct the 3D hip anatomy froma 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a populationbased cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120men with a hip fracture (<10 years frombaseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, Delta AUROC = 0.06) and fallers (Delta AUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.
|
|
| 50. |
- Grassi, Lorenzo, et al.
(författare)
-
3d Finite Element Models Reconstructed From 2d Dxa Images Improve Hip Fracture Prediction Compared to Areal Bmd in Mros Sweden Cohort
- 2023
-
Ingår i: Journal of Bone and Mineral Research. - 1523-4681. ; 38:9, s. 1258-1267
-
Tidskriftsartikel (refereegranskat)abstract
- Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (MrOS Sweden). We defined two sub-cohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and 2 controls to each hip fracture case, matched by age, height, and body mass index; (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperform aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.
|
|
