| 1. |
- Aslam, Tayyba N., et al.
(author)
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A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure
- 2023
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In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394
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Journal article (peer-reviewed)abstract
- BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
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| 2. |
- Evans Axelsson, Susan, et al.
(author)
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Targeting free prostate-specific antigen for in vivo imaging of prostate cancer using a monoclonal antibody specific for unique epitopes accessible on free prostate-specific antigen alone
- 2012
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In: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 27:4, s. 243-251
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Journal article (peer-reviewed)abstract
- This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected 125I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting 125I-labeled PSA30. Tissue uptake of 125I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, 18F-fluoro-deoxy-glucose (18F-FDG) or 18F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high 125I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either 18F-FDG or 18F-choline. Biodistribution of 125I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24–48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.
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| 3. |
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| 4. |
- Alsved, Malin, et al.
(author)
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Sources of Airborne Norovirus in Hospital Outbreaks
- 2020
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 70:10, s. 2023-2028
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Noroviruses are the major cause of viral gastroenteritis. Disease transmission is difficult to prevent and outbreaks in healthcare facilities commonly occur. Contact with infected persons and contaminated environments are believed to be the main routes of transmission. However, noroviruses have recently been found in aerosols and airborne transmission has been suggested. The aim of our study was to investigate associations between symptoms of gastroenteritis and presence of airborne norovirus, and to investigate the size of norovirus carrying particles.METHODS: Air sampling was repeatedly performed close to 26 patients with norovirus infections. Samples were analysed for norovirus RNA by RT-qPCR. The times since the patients' last episodes of vomiting and diarrhoea were recorded. Size separating aerosol particle collection was also performed in ward corridors.RESULTS: Norovirus RNA was found in 21 (24%) of 86 air samples from 10 different patients. Only air samples during outbreaks, or before a succeeding outbreak, tested positive for norovirus RNA. Airborne norovirus RNA was also strongly associated with a shorter time period since the last vomiting episode (odds ratio 8.1, p=0.04 within 3 hours since the last vomiting episode). The concentration of airborne norovirus ranged from 5-215 copies/m3, and detectable amounts of norovirus RNA were found in particles <0.95 µm and >4.51 µm.CONCLUSIONS: The results suggest that recent vomiting is the major source of airborne norovirus and imply a connection between airborne norovirus and outbreaks. The presence of norovirus RNA in submicrometre particles indicates that airborne transmission can be an important transmission route.
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| 5. |
- Bergman, Eva, et al.
(author)
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Synthesis of theoretical and empirical experineces from nutrient and cyprinid reductions in Lake Ringsjön
- 1999
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In: Hydrobiologia. - 0018-8158. ; 404, s. 145-156
-
Journal article (peer-reviewed)abstract
- The reduction in external phosphorus load to Lake Ringsjön during the 1980s, did not result in improved water transparency during the following ten-year period. Furthermore, a fish-kill in the Eastern Basin of the lake, in addition to a cyprinid reduction programme (biomanipulation; 1988–1992), in contrast to theory, did not lead to any increase in zooplankton biomass or size. This absence of response in the pelagic food chain may have been attributed to the increase in abundance of YOY (0+) fish, following the fish reduction programme. Despite the lack of effect on zooplankton, there was a decrease in phytoplankton biomass, a change in species composition and an increase in water transparency following biomanipulation. In 1989, one year after the fish-kill in Eastern Basin, the Secchi depth (summer mean) increased from 60 cm to 110 cm. In the following years, water transparency increased further, despite an increase in phosphorus loading. An unexpected effect of the biomanipulation was an increase in benthic invertebrate and staging waterfowl abundances, which occurred 2–4 years after fish reduction. Hence, the response in the benthic community following biomanipulation was considerably stronger than in the pelagic community. A likely explanation is that reduction in abundance of the benthic feeding fish species bream (Abramis brama), strongly affected the benthic invertebrate fauna. In this paper, we present what we believe happened in Lake Ringsjön, and which processes are likely to have been important at various stages of the restoration process.
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| 6. |
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| 7. |
- Kristiansson, Amanda, et al.
(author)
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177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging
- 2021
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In: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
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Journal article (peer-reviewed)abstract
- Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.
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| 8. |
- Kristiansson, Amanda, et al.
(author)
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Hematological Toxicity in Mice after High Activity Injections of 177Lu-PSMA-617
- 2022
-
In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:4
-
Journal article (peer-reviewed)abstract
- Prostate cancer (PC) is one of the most common malignancies affecting men, with poor prognosis after progression to metastatic castration-resistant prostate cancer (mCRPC). Radioligand therapy (RLT) targeting the overexpressed PSMA on PC cells, with, e.g., 177Lu-PSMA-617, has been effective in reducing tumor burden and prolonging survival in mCRPC. However, it is not a curative method with kidney and bone marrow toxicity limiting the activity given to patients. Previous preclinical models have reported transient hematotoxicity for up to 120 MBq. This activity may still be too low to investigate the effect on renal function since it corresponds to an absorbed dose below 10 Gy, whereas the kidneys in a clinical setting usually receive an absorbed dose more than double. Here we investigated the hematotoxicity and recovery after administered activities of 120, 160, and 200 MBq in a 177Lu-PSMA-617 BALB/cAnNRj mouse model. The animals had an initial drop in white blood cells (WBC) starting 4 days post injection, which recovered after 21 days. The effect on red blood cells (RBC) and platelets was detected later; 17 days post-injection levels decreased compared to the control group. The reduction was restored again 32 days post injection. No correlation between injected activity and hematotoxicity was found. Our results suggest that activities up to 200 MBq of 177Lu-PSMA-617 give transient hematotoxicity from which animals recover within a month and no radiation-related deaths. Injecting these high activities could allow animal studies with increased clinical relevance when studying renal toxicity in animal models.
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| 9. |
- Perner, Anders, et al.
(author)
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Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis
- 2012
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:2, s. 124-134
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Journal article (peer-reviewed)abstract
- BACKGROUND Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.4 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.4 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
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| 10. |
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| 11. |
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| 12. |
- Vilhelmsson Timmermand, Oskar, et al.
(author)
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A conjugation strategy to modulate antigen binding and FcRn interaction leads to improved tumor targeting and radioimmunotherapy efficacy with an antibody targeting prostate-specific antigen
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
-
Journal article (peer-reviewed)abstract
- Background: The humanized monoclonal antibody (mAb) hu5A10 specifically targets and internalizes prostate cancer cells by binding to prostate specific antigen (PSA). Preclinical evaluations have shown that hu5A10 is an excellent vehicle for prostate cancer (PCa) radiotheranostics. We studied the impact of different chelates and conjugation ratios on hu5A10′ s target affinity, neonatal fc-receptor interaction on in vivo targeting efficacy, and possible enhanced therapeutic efficacy. Methods: In our experiment, humanized 5A10 (hu5A10) was conjugated with DOTA or DTPA at a molar ratio of 3:1, 6:1, and 12:1. Surface plasmon resonance (SPR) was used to study antigen and FcRn binding to the antibody conjugates. [111 In]hu5A10 radio-immunoconjugates were administered intravenously into BALB/c mice carrying subcutaneous LNCaP xenografts. Serial Single-photon emission computed tomography (SPECT) images were obtained during the first week. Tumors were harvested and radionuclide distribution was analyzed by autoradiography along with microanatomy and immunohistochemistry. Results: As seen by SPR, the binding to PSA was clearly affected by the chelate-to-antibody ratio. Similarly, FcRn (neonatal fc-receptor) interacted less with antibodies conjugated at high ratios of chelator, which was more pronounced for DOTA conjugates. The autoradiography data indicated a higher distribution of radioactivity to the rim of the tumor for lower ratios and a more homogenous distribution at higher ratios. Mice injected with ratio 3:1111 In-DOTA-hu5A10 showed no significant difference in tumor volume when compared to mice given vehicle over a time period of 3 weeks. Mice given a similar injection of ratio 6:1111 In-DOTA-hu5A10 or 6:1111 In-DTPA-hu5A10 or 12:1111 In-DTPA-hu5A10 showed significant tumor growth retardation. Conclusions: The present study demonstrated that the radiolabeling strategy could positively modify the hu5A10′ s capacity to bind PSA and complex with the FcRn-receptor, which resulted in more homogenous activity distribution in tumors and enhanced therapy efficacy.
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| 13. |
- Abouzayed, Ayman, et al.
(author)
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Co-injection of anti-HER2 antibody Trastuzumab does not increase efficacy of [Lu-177]Lu-PSMA-617 therapy in an animal model of prostate cancer
- 2023
-
In: American Journal of Nuclear Medicine and Molecular Imaging. - : E-CENTURY PUBLISHING CORP. - 2160-8407. ; 13:3, s. 107-
-
Journal article (peer-reviewed)abstract
- One novel option for treating metastatic castration resistant prostate cancer is radionuclide therapy targeting prostate-specific membrane antigen (PSMA), e.g. [Lu-177]Lu-PSMA-617. Overexpression of HER2 has been found in 80% of metastatic cases of prostate cancer. Previous research showed that HER2 is elevated post irradiation in PC-3 prostate cancer cells. Co-treating with anti-HER2 antibody Trastuzumab gave less proliferation of irradiated tumor cells in vitro, and when using radionuclide therapy, also in vivo. The aim of this study is to determine whether the same holds true in PSMA-expressing PC-3 PIP cells using [Lu-177]Lu-PSMA-617 radionuclide therapy. PC-3 PIP and 22Rv1 prostate cancer cells were tested in vitro, treated with 6 Gy of x-rays with or without Trastuzumab incubation. We measured uptake of HER2-targeting affibody [Ga-68]Ga-ABY-025 and cell survival, e.g. using the WST-1 assay. Three groups (n=10 each) of male nude Balb/c mice were inoculated with PC-3 PIP xenograft tumors and treated with just [Lu-177]Lu-PSMA-617 (20 MBq), [Lu-177]Lu-PSMA-617 (20 MBq) and Trastuzumab (4 x 5 mg/kg), or left untreated. Tumor sizes and animal survival was observed. In vitro, x-ray irradiation did reduce survival in 22Rv1 but not PC-3 PIP cells, and there was no significant effect of Trastuzumab treatment. Cells expressed HER2 but not significantly elevated post irradiation. In vivo, mice co-treated with Trastuzumab had significantly longer survival than untreated mice, but not than only [Lu-177]Lu-PSMA-617. Staining of tumor sections showed similar HER2 and PSMA expression across groups. In conclusion, these results give no support for any benefit from co-treatment with anti-HER2 antibody for PSMA-targeted radioligand therapy.
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| 14. |
- Alanärä, Anders, et al.
(author)
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FOMA-projekt - Fiskodlingens närsaltsbelastning
- 2011
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Reports (other academic/artistic)abstract
- De huvudsakliga miljöeffekterna från fiskodling är; utsläpp av närsalter och eutrofieringsproblem, rymning av fisk som kan konkurrera med och genetiskt ”förorena” vilda bestånd, samt spridning av sjukdomar från odlad fisk till vild. Fokus i detta projekt har legat på närsalterna, specifikt fosfor och dess effekt på primärproduktionen. Syftet med studien var att (1) klargöra de huvudsakliga närsaltseffekterna av fiskodling genom att systematiskt analysera kontrollprogram, (2) belägga vilka typer av vattenområden som är lämpliga för odling, samt (3) ge förslag till en ny modell för att beräkna lämplig produktionsvolym utifrån ett givet närsaltsutrymme. Av 191 undersökta odlingar uppfyllde 13 odlingar urvalskriterier för att ingå i utvärderingen: odlingen skall ligga i sötvatten (sjö eller kraftverksmagasin), bedrivit verksamhet under minst 10 år, program för recipientkontroll skall finnas tillgängliga, samt att odlingens produktion under perioden skall finnas dokumenterad. I 11 av 13 studerade vattenområden kan vi inte observera någon negativ effekt av fiskodlingens fosforbelastning på vare sig fosfor- eller klorofyllhalter. I fem fall har fosforhalterna tydligt minskat under mätperioden och i sex fall är situationen oförändrad. Endast i två fall kan vi notera en ökning av fosforhalten vid odlingarnas kontrollstationer under mätperioden, vilket avviker från trenden vid referensstationerna. En fullständig analys av fosforbelastningen i respektive område måste dock genomföras innan orsaken till ökningen kan tillskrivas fiskodlingarna. En analys av de parametrar som påverkar odlingspotentialen (ton fisk per år) i respektive område visar att vattenflödet genom systemet och vattnets omsättningstid är av störst betydelse. Tolv av 13 odlingar är lokaliserade i områden påverkade av vattenkraften, d v s ligger i regleringsmagasin som ofta kännetecknas av högt vattenflöde och lång omsättningstid. För en framtida utveckling av svensk fiskodling, föreslås att regleringsmagasin skall vara prioriterade för nyetableringar och ökade tillstånd i befintliga odlingar. Dels för att odlingspotentialen vanligen är god i dessa områden, dels för att miljösituationen i stort är negativt påverkad av regleringen. En ny modell för bedömning av fiskodlingars fosforpåverkan har testats inom ramen för detta projekt. Vi tror att denna modell kan fungera som ett viktigt redskap för skattning av lämplig produktionsvolym vid nya ansökningar om odlingstillstånd, samt vid ansökningar om ökat tillstånd i befintliga odlingar
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| 15. |
- Almqvist, Monica, et al.
(author)
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European Medical Imaging Technology Training, EMIT – ett prisbelönt EU-utbildningsprojekt
- 2005
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In: [Host publication title missing].
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Conference paper (peer-reviewed)abstract
- I ett sameuropeiskt Leonardo da Vinci-projekt har utvecklats ett internationellt utbildnings- och praktikpa- ket för blivande sjukhusfysiker [1-3]. Utbildningspaketet innehåller praktiska och kliniska övningsuppgifter där delta- garna tränas i för en sjukhusfysiker vanligt förekommande arbetsuppgifter. Målet har varit att det skall ge sjukhusfysi- kern den praktiska kompetens som krävs av det europeiska regelverket inom ämnesområdena magnetresonans (MRI), ultraljud, röntgendiagnostik, nuklearmedicin och strålbe- handling. Utbildningsmaterialet är webbaserat med en stor bilddata- bas och används redan i nära 70 länder runt om i världen. EMIT-projektet (European Medical Imaging Technology Training) belönades i december 2004 med det första Leonar- do da Vinci priset som delades ut till de tre bästa av totalt 4000 EU-projekt inom praktisk yrkesrelaterad utbildning. I projektet har vi konfronterats med den pedagogiska ut- maningen att förmedla praktisk kunskap, i sjukhusmiljöer med mycket olika förutsättningar beroende på vilket land deltagarna arbetar i. En omöjlig uppgift kan tyckas, men eftersom materialet är sammanställt av några av Europas starkaste forsknings- och utbildningsgrupper inom respekti- ve område så har det visat sig vara en stor tillgång och varje användare utnyttjar materialet efter sina egna behov. En an- nan erfarenhet är samarbetet över nationsgränser där vi har utnyttjat och konfronterats med likheter och oliktänkande inte minst vad gäller pedagogik och didaktik. Vi har dessut- om fått ett stort kontaktnät och många goda vänner. Den här presentationen beskriver delar av utbildningspaketet och erfarenheter av samarbetsprojektet.
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| 16. |
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| 17. |
- Andersson, Emma K, 1978-, et al.
(author)
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Small molecule screening using a whole cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel anti-adenoviral compound
- 2010
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In: Antimicrobial Agents and Chemotherapy. - : American society for microbiology. - 0066-4804 .- 1098-6596. ; 54:9, s. 3871-3877
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Journal article (peer-reviewed)abstract
- Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their anti-adenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential anti-adenoviral compounds. The assay is unique in that it is based on a replication competent adenovirus type 11p GFP-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by >/= 80% but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.
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| 18. |
- Anthon, Carl Thomas, et al.
(author)
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Platelet transfusions in adult ICU patients with thrombocytopenia : A sub-study of the PLOT-ICU inception cohort study
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In: Acta Anaesthesiologica Scandinavica. - 0001-5172.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown.STUDY DESIGN AND METHODS: Sub-study of the inception cohort study 'Thrombocytopenia and Platelet Transfusions in the ICU (PLOT-ICU)', including acutely admitted, adult ICU patients with thrombocytopenia (platelet count <150 × 10 9/L). The primary outcome was the number of patients receiving platelet transfusion in ICU by product type. Secondary outcomes included platelet transfusion details, platelet increments, bleeding, other transfusions and mortality. RESULTS: Amongst 504 patients with thrombocytopenia from 43 hospitals in 10 countries in Europe and the United States, 20.8% received 565 platelet transfusions; 61.0% received pooled products, 21.9% received apheresis products and 17.1% received both with a median of 2 (interquartile range 1-4) days from admission to first transfusion. The median volume per transfusion was 253 mL (180-308 mL) and pooled products accounted for 59.1% of transfusions, however, this varied across countries. Most centres (73.8%) used fixed dosing (medians ranging from 2.0 to 3.5 × 10 11 platelets/transfusion) whilst some (mainly in France) used weight-based dosing (ranging from 0.5 to 0.7 × 10 11 platelets per 10 kg body weight). The median platelet count increment for a single prophylactic platelet transfusion was 2 (-1 to 8) × 10 9/L. Outcomes of patients with thrombocytopenia who did and did not receive platelet transfusions varied. CONCLUSIONS: Among acutely admitted, adult ICU patients with thrombocytopenia, 20.8% received platelet transfusions in ICU of whom most received pooled products, but considerable variation was observed in product type, volumes and doses across countries. Prophylactic platelet transfusions were associated with limited increases in platelet counts.
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| 19. |
- Anthon, Carl Thomas, et al.
(author)
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Thrombocytopenia and platelet transfusions in ICU patients : an international inception cohort study (PLOT-ICU)
- 2023
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In: Intensive Care Medicine. - 0342-4642. ; 49:11, s. 1327-1338
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Journal article (peer-reviewed)abstract
- PURPOSE: Thrombocytopenia (platelet count < 150 × 10 9/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
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| 20. |
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| 21. |
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| 22. |
- Blomqvist, S, et al.
(author)
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Early post-traumatic changes in hemodynamics and pulmonary ventilation in alcohol-pretreated pigs
- 1987
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In: Journal of Trauma. - 0022-5282. ; 27:1, s. 40-44
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Journal article (peer-reviewed)abstract
- Time relations among trauma, pulmonary and systemic circulation, and lung function were studied in pigs. Eleven animals (b.w. 25-30 kg) were investigated under balanced anesthesia. Ventilation was mechanically controlled. Hemodynamics, pulmonary ventilation, and gas exchange were serially recorded. Seven animals were pretreated with 40% ethanol in saline and four with saline only. Ninety minutes after the ingestion of alcohol or saline, the animals were subjected to a standardized soft-tissue trauma. Cardiac output decreased significantly 2 minutes after trauma and remained low in both groups throughout the observation period of 30 minutes. Pulmonary vascular resistance was significantly increased in the alcohol-pretreated group but was virtually unchanged in the control animals. Systemic vascular resistance was similarly reduced in the two groups. Total compliance was somewhat lower in alcohol-pretreated animals and 10 minutes after the trauma arterial oxygen tension was significantly lower in the alcohol group than in control animals. Carbon dioxide elimination was reduced after trauma in both groups. It is concluded that pulmonary vascular response increased and that total pulmonary compliance is somewhat decreased shortly after trauma in the alcohol group while gas exchange is almost unchanged. The results indicate a negative interaction between alcohol and trauma
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| 23. |
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| 24. |
- Bombarda, F., et al.
(author)
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Runaway electron beam control
- 2019
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Journal article (peer-reviewed)
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| 25. |
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| 26. |
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| 27. |
- Bréchignac, Francois, et al.
(author)
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Addressing ecological effects of radiation on populations and ecosystems to improve protection of the environment against radiation : Agreed statements from a Consensus Symposium
- 2016
-
In: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 158, s. 21-29
-
Research review (peer-reviewed)abstract
- This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to consider the still debated ecological impact of radiation on populations and ecosystems. Stimulated by the Chernobyl and Fukushima disasters' accidental contamination of the environment, there is increasing interest in developing environmental radiation protection frameworks. Scientific research conducted in a variety of laboratory and field settings has improved our knowledge of the effects of ionizing radiation on the environment. However, the results from such studies sometimes appear contradictory and there is disagreement about the implications for risk assessment. The Symposium discussions therefore focused on issues that might lead to different interpretations of the results, such as laboratory versus field approaches, organism versus population and ecosystemic inference strategies, dose estimation approaches and their significance under chronic exposure conditions. The participating scientists, from across the spectrum of disciplines and research areas, extending also beyond the traditional radioecology community, successfully developed a constructive spirit directed at understanding discrepancies. From the discussions, the group has derived seven consensus statements related to environmental protection against radiation, which are supplemented with some recommendations. Each of these statements is contextualized and discussed in view of contributing to the orientation and integration of future research, the results of which should yield better consensus on the ecological impact of radiation and consolidate suitable approaches for efficient radiological protection of the environment.
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| 28. |
- Brun, Eva, et al.
(author)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
-
Journal article (peer-reviewed)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 29. |
- Brun, Eva, et al.
(author)
-
FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
-
In: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 30. |
- Callier, Myriam D., et al.
(author)
-
Attraction and repulsion of mobile wild organisms to finfish and shellfish aquaculture: A review
- 2018
-
In: Reviews in Aquaculture. - : Wiley. - 1753-5123 .- 1753-5131. ; 10:4, s. 924-949
-
Journal article (peer-reviewed)abstract
- © 2017 Wiley Publishing Asia Pty Ltd. Knowledge of aquaculture-environment interactions is essential for the development of a sustainable aquaculture industry and efficient marine spatial planning. The effects of fish and shellfish farming on sessile wild populations, particularly infauna, have been studied intensively. Mobile fauna, including crustaceans, fish, birds and marine mammals, also interact with aquaculture operations, but the interactions are more complex and these animals may be attracted to (attraction) or show an aversion to (repulsion) farm operations with various degrees of effects. This review outlines the main mechanisms and effects of attraction and repulsion of wild animals to/from marine finfish cage and bivalve aquaculture, with a focus on effects on fisheries-related species. Effects considered in this review include those related to the provision of physical structure (farm infrastructure acting as fish aggregating devices (FADs) or artificial reefs (ARs), the provision of food (e.g. farmed animals, waste feed and faeces, fouling organisms associated with farm structures) and some farm activities (e.g. boating, cleaning). The reviews show that the distribution of mobile organisms associated with farming structures varies over various spatial (vertical and horizontal) and temporal scales (season, feeding time, day/night period). Attraction/repulsion mechanisms have a variety of direct and indirect effects on wild organisms at the level of individuals and populations and may have implication for the management of fisheries species and the ecosystem in the context of marine spatial planning. This review revealed considerable uncertainties regarding the long-term and ecosystem-wide consequences of these interactions. The use of modelling may help better understand consequences, but long-term studies are necessary to better elucidate effects.
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| 31. |
- 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
-
In: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 57:24, s. 8377-8391
-
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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| 32. |
- Citrin, J., et al.
(author)
-
Tractable flux-driven temperature, density, and rotation profile evolution with the quasilinear gyrokinetic transport model QuaLiKiz
- 2017
-
In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 59:12
-
Journal article (peer-reviewed)abstract
- Quasilinear turbulent transport models are a successful tool for prediction of core tokamak plasma profiles in many regimes. Their success hinges on the reproduction of local nonlinear gyrokinetic fluxes. We focus on significant progress in the quasilinear gyrokinetic transport model QuaLiKiz (Bourdelle et al 2016 Plasma Phys. Control. Fusion 58 014036), which employs an approximated solution of the mode structures to significantly speed up computation time compared to full linear gyrokinetic solvers. Optimisation of the dispersion relation solution algorithm within integrated modelling applications leads to flux calculations x 10(6-7) faster than local nonlinear simulations. This allows tractable simulation of flux-driven dynamic profile evolution including all transport channels: ion and electron heat, main particles, impurities, and momentum. Furthermore, QuaLiKiz now includes the impact of rotation and temperature anisotropy induced poloidal asymmetry on heavy impurity transport, important for W-transport applications. Application within the JETTO integrated modelling code results in 1 s of JET plasma simulation within 10 h using 10 CPUs. Simultaneous predictions of core density, temperature, and toroidal rotation profiles for both JET hybrid and baseline experiments are
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| 33. |
- Dalén, Love, et al.
(author)
-
Population structure in a critically endangered arctic fox population : does genetics matter?
- 2006
-
In: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 15:10, s. 2809-2819
-
Journal article (peer-reviewed)abstract
- The arctic fox (Alopex lagopus) in Scandinavia is classified as critically endangered after having gone through a severe decline in population size in the beginning of the 20th century, from which it has failed to recover despite more than 65 years of protection. Arctic foxes have a high dispersal rate and often disperse over long distances, suggesting that there was probably little population differentiation within Scandinavia prior to the bottleneck. It is, however, possible that the recent decline in population size has led to a decrease in dispersal and an increase in population fragmentation. To examine this, we used 10 microsatellite loci to analyse genetic variation in 150 arctic foxes from Scandinavia and Russia. The results showed that the arctic fox in Scandinavia presently is subdivided into four populations, and that the Kola Peninsula and northwest Russia together form a large fifth population. Current dispersal between the populations seemed to be very low, but genetic variation within them was relatively high. This and the relative F-ST values among the populations are consistent with a model of recent fragmentation within Scandinavia. Since the amount of genetic variation is high within the populations, but the populations are small and isolated, demographic stochasticity seems to pose a higher threat to the populations' persistence than inbreeding depression and low genetic variation.
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| 34. |
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| 35. |
- Elfgren, Kristina, et al.
(author)
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Colposcopic and histopathologic evaluation of women participating in population-based screening for human papillomavirus deoxyribonucleic acid persistence
- 2005
-
In: Am J Obstet Gynecol. - : Elsevier BV. ; 193:3, s. 650-657
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Evaluation of colposcopic and histopathological findings in women screened for cervical human papillomavirus deoxyribonucleic acid persistence. STUDY DESIGN: A total of 12 527 women, aged 32 to 38 years old, attending the population-based cervical cancer screening program in Sweden were randomized 1:1 to mock testing or human papillomavirus deoxyribonucleic acid testing by general primer 5+/6+ polymerase chain reaction and subsequent typing. Human papillomavirus deoxyribonucleic acid-positive women with a normal Papanicolaou smear (n=341) and an equal number from the control group were human papillomavirus tested on average 19 months later. One hundred nineteen women with type-specific human papillomavirus persistence and 111 controls were referred to colposcopy, and 84.8% attended. RESULTS: Histopathology from colposcopically directed biopsies confirmed cervical intraepithelial neoplasia grade 2 or 3 in 28 of 100 of the women with human papillomavirus deoxyribonucleic acid persistence and in 2 of 95 among controls. CONCLUSION: Among women with normal Papanicolaou smear attending population-based screening, the positive predictive value of human papillomavirus deoxyribonucleic acid persistence for detection of biopsy-confirmed cervical intraepithelial neoplasia 2 or 3 was 29%.
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| 36. |
- Elgström, Erika, et al.
(author)
-
Change in Cell Death Markers During (177)Lu-mAb Radioimmunotherapy-Induced Rejection of Syngeneic Rat Colon Carcinoma.
- 2014
-
In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 29:4, s. 143-152
-
Journal article (peer-reviewed)abstract
- Abstract Purpose: To monitor cell death in tumors during the rejection process after treatment with an antibody radiolabeled with a β-emitter. Methods: Tumors during rejection after treatment with (177)Lu-labeled antibody BR96 and after administration of unlabeled BR96 were compared with untreated tumors from the same immunocompetent syngeneic rat tumor model. Cell death was monitored with the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical staining of activated caspase-3 and γH2AX. These data were evaluated together with histopathological morphology, BR96-binding antigen expression, and (177)Lu radioactivity distribution imaged by digital autoradiography. Results: The untreated tumors showed staining for all the markers, mainly in and around the necrotic areas. One to 2 days p.i. large areas were stained with anti-γH2AX, followed by a slight decrease. Staining of activated caspase-3 was intense and extensive 1-2 days p.i., while found in and around necrotic areas 3-8 days p.i. TUNEL staining was similar to activated caspase-3 staining 1-2 days p.i. but more extensive than activated caspase-3 staining 3-4 days p.i. Digital autoradiography revealed activity concentration in granulation tissue from 1 day p.i. Conclusion: Following radioimmunotherapy in an immunocompetent syngeneic colon carcinoma model, tumor cells did not only die through caspase-3-dependent apoptosis, but also by other mechanisms.
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| 37. |
- Enbom, Malin, et al.
(author)
-
Detection of Epstein-Barr virus, but not human herpesvirus 8, DNA in cervical secretions from Swedish women by real-time polymerase chain reaction
- 2001
-
In: Sexually Transmitted Diseases. - : Ovid Technologies (Wolters Kluwer Health). - 0148-5717 .- 1537-4521. ; 28:5, s. 300-306
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) are two related herpesviruses that may be sexually transmitted. GOAL: To examine the presence of HHV-8 and EBV DNA in the female genital tract. STUDY DESIGN: Real-time polymerase chain reaction systems for quantification of DNA from HHV-8, EBV, and herpes simplex virus type 2 were developed and used for examination of cervical secretions from 112 Swedish women. HHV-8, EBV, and herpes simplex virus type 2 serology was also performed on samples from all subjects. RESULTS: EBV DNA was found in 10 cervical secretion samples, sometimes in high amounts. No cervical secretion or leukocyte sample contained detectable HHV-8 DNA. Antibodies to HHV-8-latent and -lytic antigens were found in 2.7 % and 24% of serum samples, respectively. CONCLUSION: This study supports a possible sexual route of transmission for EBV but not for HHV-8. The new real-time polymerase chain reaction systems could be valuable in future studies of relations between virus load and disease
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| 38. |
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| 39. |
- Eriksson, Frida, 1986, et al.
(author)
-
Impact of fast ions on density peaking in JET : fluid and gyrokinetic modeling
- 2019
-
In: Plasma Physics and Controlled Fusion. - : Institute of Physics Publishing (IOPP). - 0741-3335 .- 1361-6587. ; 61:7
-
Journal article (peer-reviewed)abstract
- The effect of fast ions on turbulent particle transport, driven by ion temperature gradient (ITG)/trapped electron mode turbulence, is studied. Two neutral beam injection (NBI) heated JET discharges in different regimes are analyzed at the radial position rho(t) = 0.6, one of them an L-mode and the other one an H-mode discharge. Results obtained from the computationally efficient fluid model EDWM and the gyro-fluid model TGLF are compared to linear and nonlinear gyrokinetic GENE simulations as well as the experimentally obtained density peaking. In these models, the fast ions are treated as a dynamic species with a Maxwellian background distribution. The dependence of the zero particle flux density gradient (peaking factor) on fast ion density, temperature and corresponding gradients, is investigated. The simulations show that the inclusion of a fast ion species has a stabilizing influence on the ITG mode and reduces the peaking of the main ion and electron density profiles in the absence of sources. The models mostly reproduce the experimentally obtained density peaking for the L-mode discharge whereas the H-mode density peaking is significantly underpredicted, indicating the importance of the NBI particle source for the H-mode density profile.
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| 40. |
- Eriksson, Frida, 1986, et al.
(author)
-
Interpretative and predictive modelling of Joint European Torus collisionality scans
- 2019
-
In: Plasma Physics and Controlled Fusion. - : Institute of Physics Publishing (IOPP). - 0741-3335 .- 1361-6587. ; 61:11
-
Journal article (peer-reviewed)abstract
- Transport modelling of Joint European Torus (JET) dimensionless collisionality scaling experiments in various operational scenarios is presented. Interpretative simulations at a fixed radial position are combined with predictive JETTO simulations of temperatures and densities, using the TGLF transport model. The model includes electromagnetic effects and collisions as well as (E)over-right-arrow x (b)over-right-arrow shear in Miller geometry. Focus is on particle transport and the role of the neutral beam injection (NBI) particle source for the density peaking. The experimental 3-point collisionality scans include L-mode, and H-mode (D and H and higher beta D plasma) plasmas in a total of 12 discharges. Experimental results presented in (Tala et al 2017 44th EPS Conf.) indicate that for the H-mode scans, the NBI particle source plays an important role for the density peaking, whereas for the L-mode scan, the influence of the particle source is small. In general, both the interpretative and predictive transport simulations support the experimental conclusions on the role of the NBI particle source for the 12 JET discharges.
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| 41. |
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| 42. |
- Eriksson-Strand, Johanna, et al.
(author)
-
Snowmobilie fatalities in Sweden, 1999-2006
- 2007
-
In: Proceedings of the 6th International congress of the baltic medico-legal association. ; , s. S13-
-
Conference paper (other academic/artistic)
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| 43. |
- Evans Axelsson, Susan, et al.
(author)
-
Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.
- 2014
-
In: American journal of nuclear medicine and molecular imaging. - 2160-8407. ; 4:4, s. 311-323
-
Journal article (peer-reviewed)abstract
- The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.
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| 44. |
- Evans Axelsson, Susan, et al.
(author)
-
Radioimmunotherapy for Prostate Cancer-Current Status and Future Possibilities.
- 2016
-
In: Seminars in Nuclear Medicine. - : Elsevier BV. - 0001-2998. ; 46:2, s. 165-179
-
Research review (peer-reviewed)abstract
- Prostate cancer (PCa) is one of the most common cancers in men and is the second leading cause of cancer-related deaths in the USA. In the United States, it is the second most frequently diagnosed cancer after skin cancer, and in Europe it is number one. According to the American Cancer Society, approximately 221,000 men in the United States would be diagnosed with PCa during 2015, and approximately 28,000 would die of the disease. According to the International Agency for Research on Cancer, approximately 345,000 men were diagnosed with PCa in Europe during 2012, and despite more emphasis placed on early detection through routine screening, 72,000 men died of the disease. Hence, the need for improved therapy modalities is of utmost importance. And targeted therapies based on radiolabeled specific antibodies or peptides are a very interesting and promising alternative to increase the therapeutic efficacy and overall chance of survival of these patients. There are currently several preclinical and some clinical studies that have been conducted, or are ongoing, to investigate the therapeutic efficacy and toxicity of radioimmunotherapy (RIT) against PCa. One thing that is lacking in a lot of these published studies is the dosimetry data, which are needed to compare results between the studies and the study locations. Given the complicated tumor microenvironment and overall complexity of RIT to PCa, old and new targets and targeting strategies like combination RIT and pretargeting RIT are being improved and assessed along with various therapeutic radionuclides candidates. Given alone or in combination with other therapies, these new and improved strategies and RIT tools further enhance the clinical response to RIT drugs in PCa, making RIT for PCa an increasingly practical clinical tool.
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| 45. |
- Filén, Finn, et al.
(author)
-
Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions
- 2004
-
In: Sexually Transmitted Diseases. - 0148-5717 .- 1537-4521. ; 31:6, s. 331-6
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A sensitive and specific method for detecting herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) is important for diagnosing genital and cutaneous infections. GOAL: The goal of this study was to compare quantitative real-time polymerase chain reaction (qPCR) with virus culture for diagnosis of genital and cutaneous HSV-1 and HSV-2. STUDY DESIGN: A duplex qPCR system for quantification of DNA from HSV-1 and HSV-2 was developed. Duplicate swabs for PCR and virus culture were collected from 89 patients attending our sexually transmitted infection and dermatology clinic. RESULTS: The duplex qPCR had a linear measure interval of 10-10 copies/mL. The detection limit was between 1 and 5 copies per reaction. qPCR detected HSV in 57 (64%) specimens and virus was isolated in 45 (50%) cases. First-episode infections showed higher viral quantities with a median value of 4.2 x 10 copies per reaction compared with recurrent infections with 1.0 x 10 (P = 0.0002). HSV-1 was more likely to be the cause of first-episode genital infections (72%), and HSV-2 of recurrent and atypical genital manifestations (73%). CONCLUSION: Real-time PCR is a sensitive method for diagnosing genital herpes, and the duplex format is convenient for typing. The method increased the detection rate by 27% compared with virus culture.
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| 46. |
- Forslund, Ola, et al.
(author)
-
Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish Women.
- 2002
-
In: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 66:4, s. 535-541
-
Journal article (peer-reviewed)abstract
- Human papillomavirus (HPV) DNA testing can be used to identify women at risk of the development of cervical cancer. The cost-effectiveness of HPV screening is dependent on the type-specific HPV prevalence in the general population. The present study describes the prevalence and spectrum of high-risk HPV types found in a large real-life population-based HPV screening trial undertaken entirely within the cervical screening program offered to middle-aged Swedish women. Cervical brush samples from 6,123 women aged 32-38 years were analyzed using a general HPV primer (GP5(+)/6(+)) polymerase chain reaction-enzyme immunoassay (PCR-EIA) combined with reverse dot-blot hybridization for confirmation and HPV typing by a single assay. In this study, 6.8% (95% CI 6.2-7.5) (417/6,123) were confirmed as high-risk HPV positive. Infections with 13 different high-risk HPV types were detected, of which HPV 16 was the most prevalent type (2.1%; 128/6,123), followed by HPV 31 (1.1%; 67/6,123). Any one of the HPV types 18, 33, 35, 39, 45, 51, 52, 56, 58, 59, or 66 was detected in 3.6% (223/6,123) of the women. Infection with two, three, and five types simultaneously was identified in 32, 5, and 1 women, respectively. The combination of PCR-EIA as a screening test and reverse dot-blot hybridization as a confirmatory test, was found to be readily applicable to a real-life population-based cervical screening. The type-specific HPV prevalence found support in previous modeling studies suggesting that HPV screening may be a favorable cervical screening strategy.
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| 47. |
- Fransson, Samuel, et al.
(author)
-
Intrafractional motion models based on principal components in Magnetic Resonance guided prostate radiotherapy
- 2021
-
In: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 20, s. 17-22
-
Journal article (peer-reviewed)abstract
- Background and purpose: Devices that combine an MR-scanner with a Linac for radiotherapy, referred to as MR-Linac systems, introduce the possibility to acquire high resolution images prior and during treatment. Hence, there is a possibility to acquire individualised learning sets for motion models for each fraction and the construction of intrafractional motion models. We investigated the feasibility for a principal component analysis (PCA) based, intrafractional motion model of the male pelvic region.Materials and methods: 4D-scans of nine healthy male volunteers were utilized, FOV covering the entire pelvic region including prostate, bladder and rectum with manual segmentation of each organ at each time frame. Deformable image registration with an optical flow algorithm was performed for each subject with the first time frame as reference. PCA was performed on a subset of the resulting displacement vector fields to construct individualised motion models evaluated on the remaining fields.Results: The registration algorithm produced accurate registration result, in general DICE overlap >0.95 across all time frames. Cumulative variance of the eigen values from the PCA showed that 50% or more of the motion is explained in the first component for all subjects. However, the size and direction for the components differed between subjects. Adding more than two components did not improve the accuracy significantly and the model was able to explain motion down to about 1 mm.onclusions: An individualised intrafractional male pelvic motion model is feasible. Geometric accuracy was about 1 mm based on 1-2 principal components.
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| 48. |
- Fridolfsson, Charlotte, et al.
(author)
-
Ideologi i makt och motstånd
- 2016
-
In: Fronesis. - 1404-2614. ; :52-53, s. 8-21
-
Journal article (other academic/artistic)
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| 49. |
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| 50. |
- George, Ian R., et al.
(author)
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A Unifying Bioinspired Synthesis of (-)-Asperaculin A and (-)-Penifulvin D
- 2021
-
In: Organic Letters. - : American Chemical Society (ACS). - 1523-7060 .- 1523-7052. ; 23:9, s. 3536-3540
-
Journal article (peer-reviewed)abstract
- The first syntheses of the isomeric dioxafenestrene natural products (-)-asperaculin A and (-)-penifulvin D are reported. Each target is formed selectively by choice of oxidant in a final divergent bioinspired Baeyer-Villiger (BV) reaction. Density functional theory calculations reveal that electrostatic interactions between the oxidant leaving group and the lactone motif accounts for a reversal of selectivity with H2O2/H3O+ compared to peracids. Synthetic features include forging the polycyclic carbon framework with a diastereoselective meta-photocycloaddition biased by an ether substituent at the aryl α-position. The encumbered tertiary alcohol was installed by cyanation of a ketone intermediate followed by nonaqueous hydrolysis of the resulting delicate cyanohydrin.
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