| 1. |
|
|
| 2. |
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 4. |
- Clark, DW, et al.
(författare)
-
Associations of autozygosity with a broad range of human phenotypes
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
-
Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Fages, A., et al.
(författare)
-
Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
-
Tidskriftsartikel (refereegranskat)abstract
- Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Oddsson, Asmundur, et al.
(författare)
-
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Abdollahi, S., et al.
(författare)
-
A gamma-ray determination of the Universe's star formation history
- 2018
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 362:6418, s. 1031-1034
-
Tidskriftsartikel (refereegranskat)abstract
- The light emitted by all galaxies over the history of the Universe produces the extragalactic background light (EBL) at ultraviolet, optical, and infrared wavelengths. The EBL is a source of opacity for gamma rays via photon-photon interactions, leaving an imprint in the spectra of distant gamma-ray sources. We measured this attenuation using 739 active galaxies and one gamma-ray burst detected by the Fermi Large Area Telescope. This allowed us to reconstruct the evolution of the EBL and determine the star formation history of the Universe over 90% of cosmic time. Our star formation history is consistent with independent measurements from galaxy surveys, peaking at redshift z similar to 2. Upper limits of the EBL at the epoch of reionization suggest a turnover in the abundance of faint galaxies at z similar to 6.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Jorgensen, A. A., et al.
(författare)
-
Petabit-per-second data transmission using a chip-scale microcomb ring resonator source
- 2022
-
Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 16:11, s. 798-802
-
Tidskriftsartikel (refereegranskat)abstract
- Optical fibre communication is the backbone of the internet. As essential core technologies are approaching their limits of size, speed and energy-efficiency, there is a need for new technologies that offer further scaling of data transmission capacity. Here we show that a single optical frequency-comb source based on a silicon nitride ring resonator supports data capacities in the petabit-per-second regime. We experimentally demonstrate transmission of 1.84 Pbit s–1 over a 37-core, 7.9-km-long fibre using 223 wavelength channels derived from a single microcomb ring resonator producing a stabilized dark-pulse Kerr frequency comb. We also present a theoretical analysis that indicates that a single, chip-scale light source should be able to support 100 Pbit s–1 in massively parallel space-and-wavelength multiplexed data transmission systems. Our findings could mark a shift in the design of future communication systems, targeting device-efficient transmitters and receivers.
|
|
| 20. |
- Kong, D., et al.
(författare)
-
Single Dark-Pulse Kerr Comb Supporting 1.84 Pbit/s Transmission over 37-Core Fiber
- 2020
-
Ingår i: Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS. - 1092-8081. ; 2020-May
-
Konferensbidrag (refereegranskat)abstract
- We show that a single dark-pulse Kerr comb can generate high enough OSNR to carry 1.84 Pbit/s data, achieved by 223 WDM spectral lines modulated with 32-Gbaud, SNR-adapted probabilistically shaped DP-QAM, over a 37-core fiber.
|
|
| 21. |
- Lewis, Cathryn M, et al.
(författare)
-
Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
-
Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
-
Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
|
|
| 22. |
- Sigurdsson, Martin, I, et al.
(författare)
-
Association Between Preoperative Opioid and Benzodiazepine Prescription Patterns and Mortality After Noncardiac Surgery
- 2019
-
Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:8
-
Tidskriftsartikel (refereegranskat)abstract
- ImportanceThe number of patients prescribed long-term opioids and benzodiazepines and complications from their long-term use have increased. Information regarding the perioperative outcomes of patients prescribed these medications before surgery is limited. ObjectiveTo determine whether patients prescribed opioids and/or benzodiazepines within 6 months preoperatively would have greater short- and long-term mortality and increased opioid consumption postoperatively. Design, Setting, and ParticipantsThis retrospective, single-center, population-based cohort study included all patients 18 years or older, undergoing noncardiac surgical procedures at a national hospital in Iceland from December 12, 2005, to December 31, 2015, with follow-up through May 20, 2016. A propensity score-matched control cohort was generated using individuals from the group that received prescriptions for neither medication class within 6 months preoperatively. Data analysis was performed from April 10, 2018, to March 9, 2019. ExposuresPatients who filled prescriptions for opioids only, benzodiazepines only, both opioids and benzodiazepines, or neither medication within 6 months preoperatively. Main Outcomes and MeasuresLong-term survival compared with propensity score-matched controls. Secondary outcomes were 30-day survival and persistent postoperative opioid consumption, defined as a prescription filled more than 3 months postoperatively. ResultsAmong 41170 noncardiac surgical cases in 27787 individuals (16004 women [57.6%]; mean [SD] age, 56.3 [18.8] years), a preoperative prescription for opioids only was filled for 7460 cases (17.7%), benzodiazepines only for 3121 (7.4%), and both for 2633 (6.2%). Patients who filled preoperative prescriptions for either medication class had a greater comorbidity burden compared with patients receiving neither medication class (Elixhauser comorbidity index >0 for 16% of patients filling prescriptions for opioids only, 22% for benzodiazepines only, and 21% for both medications compared with 14% for patients filling neither). There was no difference in 30-day (opioids only: 1.3% vs 1.0%; P=.23; benzodiazepines only: 1.9% vs 1.5%; P=.32) or long-term (opioids only: hazard ratio [HR], 1.12 [95% CI, 1.01-1.24]; P=.03; benzodiazepines only: HR, 1.11 [95% CI, 0.98-1.26]; P=.11) survival among the patients receiving opioids or benzodiazepines only compared with controls. However, patients prescribed both opioids and benzodiazepines had greater 30-day mortality (3.2% vs 1.8%; P=.004) and a greater hazard of long-term mortality (HR, 1.41; 95% CI, 1.22-1.64; P<.001). The rate of persistent postoperative opioid consumption was higher for patients filling prescriptions for opioids only (43%), benzodiazepines only (23%), or both (66%) compared with patients filling neither (12%) (P<.001 for all). Conclusions and RelevanceThe findings suggest that opioid and benzodiazepine prescription fills in the 6 months before surgery are associated with increased short-and long-term mortality and an increased rate of persistent postoperative opioid consumption. These patients should be considered for early referral to preoperative clinic and medication optimization to improve surgical outcomes.
|
|
| 23. |
- Styrkarsdottir, Unnur, et al.
(författare)
-
Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
|
|
| 24. |
|
|
| 25. |
- Al-Abany, M., et al.
(författare)
-
Toward a definition of a threshold for harmless doses to the anal-sphincter region and the rectum
- 2005
-
Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 61:4, s. 1035-44
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate dysfunction caused by unwanted radiation to the anal-sphincter region and the rectum. METHODS AND MATERIALS: A questionnaire assessing bowel symptoms, sexual function, and urinary symptoms was sent to 72 patients with clinically localized prostatic adenocarcinoma treated by external beam radiation therapy at the Radiumhemmet, Karolinska Hospital, in Stockholm, Sweden, 2-4 years after treatment. The mean percentage dose-volume histograms for patients with and without the specific symptom were calculated. RESULTS: Of the 65 patients providing information, 9 reported fecal leakage, 10 blood and mucus in stools, 10 defecation urgency, and 7 diarrhea or loose stools. None of the 19 and 13 patients who received, respectively, a dose of > or =35 Gy to < or =60% or > or =40 Gy to < or =40% of the anal-sphincter region volume reported fecal leakage (p < 0.05). In dose-volume histograms, a statistically significant correlation was found between radiation to the anal-sphincter region and the risk of fecal leakage in the interval 45-55 Gy. There was also a statistically significant correlation between radiation to the rectum and the risk of defecation urgency and diarrhea or loose stools in the interval 25-42 Gy. No relationship was found between anatomic rectal wall volume and the investigated late effects. CONCLUSIONS: Although the limited data in this study prevent the definition of a conclusive threshold regarding volume and dose to the anal-sphincter region and untoward morbidity, it seems that careful monitoring of unnecessary irradiation to this area should be done because it can potentially help reduce the risk of adverse effects, such as fecal leakage. Future studies should pay more attention to the anal-sphincter region and help to more rigorously define its radiotherapeutic tolerance.
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Desai, A., et al.
(författare)
-
Probing the EBL Evolution at High Redshift Using GRBs Detected with the Fermi-LAT
- 2017
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 850:1
-
Tidskriftsartikel (refereegranskat)abstract
- The extragalactic background light (EBL), from ultraviolet to infrared wavelengths, is predominantly due to emission from stars, accreting black holes and reprocessed light due to Galactic dust. The EBL can be studied through the imprint it leaves, via gamma-gamma absorption of high-energy photons, in the spectra of distant.-ray sources. The EBL has been probed through the search for the attenuation it produces in the spectra of BL Lacertae (BL Lac) objects and individual.-ray bursts (GRBs). GRBs have significant advantages over blazars for the study of the EBL especially at high redshifts. Here we analyze a combined sample of 22 GRBs, detected by the Fermi Large Area Telescope between 65 MeV and 500 GeV. We report a marginal detection (at the similar to 2.8 sigma level) of the EBL attenuation in the stacked spectra of the source sample. This measurement represents a first constraint of the EBL at an effective redshift of similar to 1.8. We combine our results with prior EBL constraints and conclude that Fermi-LAT is instrumental to constrain the UV component of the EBL. We discuss the implications on existing empirical models of EBL evolution.
|
|
| 30. |
- Galanti, MR, et al.
(författare)
-
Smoking cessation: gender on the agenda
- 2002
-
Ingår i: DRUGS-EDUCATION PREVENTION AND POLICY. - : Informa UK Limited. - 0968-7637 .- 1465-3370. ; 9:1, s. 71-84
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Kristjansson, S., et al.
(författare)
-
Readiness to change sun-protective behaviour
- 2001
-
Ingår i: European Journal of Cancer Prevention. - : Ovid Technologies (Wolters Kluwer Health). - 0959-8278 .- 1473-5709. ; 10:3, s. 289-296
-
Tidskriftsartikel (refereegranskat)abstract
- The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden during the last 20 years. The best-known way to revert this trend is primary prevention. Matching health messages to readiness to change in the population may enhance the effect of community-based prevention. The aims of this study were to investigate readiness to change sun-protective behaviour in two groups (visitors to mobile screening units and beach-goers) and to test a single-item algorithm in assessing the stage of change in sun-protective behaviour. Seven hundred and forty-two visitors to the mobile screening units and 202 individuals on nearby beaches answered a short questionnaire. The assessment of readiness to change was based on stages of change in sun-protective behaviour modified from the Transtheoretical Model of Behaviour Change. As expected, the visitors to the screening units were more often in action/maintenance stages than the beach group for most sun-protective behaviours. In conclusion, the single-item algorithm method appears to be sensitive to assess readiness to change sun-protective behaviour, based on the Transtheoretical Model of Behaviour Change. This method can be incorporated into population surveys and may aid in developing successful skin cancer prevention programmes. © 2001 Lippincott Williams & Wilkins.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
- Long, Thorir E., et al.
(författare)
-
Postoperative Acute Kidney Injury : Focus on Renal Recovery Definitions, Kidney Disease Progression and Survival
- 2019
-
Ingår i: American Journal of Nephrology. - : KARGER. - 0250-8095 .- 1421-9670. ; 49:3, s. 175-185
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to examine different definitions of renal recovery following postoperative acute kidney injury (AKI) and how these definitions associate with survival and the development and progression of chronic kidney disease (CKD).Methods: This was a retrospective study of all patients who underwent abdominal, cardiothoracic, vascular, or orthopedic surgery at a single university hospital between 1998 and 2015. Recovery of renal function following postoperative AKI was assessed comparing 4 different definitions: serum creatinine (SCr) (i) < 1.1 x baseline, (ii) 1.1-1.25 x baseline, (iii) 1.25-1.5 x baseline, and (iv) > 1.5 x baseline. One-year survival and the development or progression of CKD within 5 years was compared with a propensity score-matched control groups.Results: In total, 2,520 AKI patients were evaluated for renal recovery. Risk of incident and progressive CKD within 5 years was significantly increased if patients did not achieve a reduction in SCr to < 1.5 x baseline (hazard ratio [HR] 1.50; 95% CI 1.29-1.75) and if renal recovery was limited to a fall in SCr to 1.25-1.5 x baseline (HR 1.32; 95% CI 1.12-1.57) within 30 days. The definition of renal recovery that best predicted survival was a reduction in SCr to < 1.5 x baseline within 30 days. One-year survival of patients whose SCr decreased to < 1.5 x baseline within 30 days was significantly better than that of a propensity score-matched control group that did not achieve renal recovery (85 vs. 71%, p < 0.001).Conclusions: These findings should be considered when a consensus definition of renal recovery after AKI is established.
|
|
| 41. |
- Lund, KE, et al.
(författare)
-
Children's residential exposure to environmental tobacco smoke varies greatly between the Nordic countries
- 1998
-
Ingår i: Scandinavian journal of social medicine. - : SAGE Publications. - 0300-8037. ; 26:2, s. 115-120
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess similarities and differences in the Nordic countries regarding ETS (environmental tobacco smoke) exposure in young children. Design: A population-based cross-sectional study comprising a randomly selected sample of 5,500 households which included a child born in 1992. Data were collected using a mailed anonymous questionnaire. Results: While the prevalence of household smoking was similar in all countries, there was a great difference between the countries with regard to child ETS exposure. Finnish parents were more likely than all other Nordic parents to protect their children from ETS and the situation was worst in Denmark and Iceland, where almost half of all households, and nine out of ten households containing daily smokers, exposed their children. Approximately eight out of ten current and former smokers in all countries stated that they had made efforts to change their smoking habits because of their children.
|
|
| 42. |
|
|
| 43. |
- Magnadottir, B., Bambir, S. H., Gudmundsdottir, B. K., Pilström, L. and Helgason, S
(författare)
-
Atypical Aeromonas salmonicida infection in naturally and experimentally infected cod, Gadus morhua L.
- 2002
-
Ingår i: J. Fish Dis.. ; 25, s. 583-597
-
Tidskriftsartikel (refereegranskat)
|
|
| 44. |
|
|
| 45. |
- Magnadóttir, B, et al.
(författare)
-
Optimisation of ELISA used to measure total serum IgM and antibody activity in different groups of cod.
- 1998
-
Ingår i: in Barnes, A.C., Davidson, G. A., Hiney, M. P., McIntosh, D. (eds.) Fish Disease Research. - : Fisheries Research Services, Aberdeen. ; , s. 105-
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 46. |
- Mavroidis, P., et al.
(författare)
-
Dose-Response Relations for Anal Sphincter Regarding Fecal Leakage and Blood or Phlegm in Stools after Radiotherapy for Prostate Cancer Radiobiological Study of 65 Consecutive Patients
- 2005
-
Ingår i: Strahlenther Onkol. - 0179-7158. ; 181:5, s. 293-306
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: : The estimation of the parameters that describe the dose-response relations of anal sphincter regarding the clinical endpoints of fecal leakage and blood or phlegm in stools is important in the optimization of prostate cancer radiotherapy. Also, the validity of the relative seriality model for this clinical case needs to be examined by associating the clinical follow-up results with the predicted complication rates. PATIENTS AND METHODS: : In this study, 65 patients who received radiation therapy for clinically localized prostate adenocarcinoma are analyzed. The clinical treatment outcome and the three-dimensional dose distribution delivered to anal sphincter were available for each patient. A questionnaire was used for assessing the clinical bowel and urinary symptoms. A maximum likelihood fitting was performed to calculate the best estimates of the parameters used by the relative seriality model. The clinical utilization of the calculated parameters in predicting anal sphincter complication probabilities was illustrated by applying the best estimate of the parameters to a subset of the patient population. RESULTS: : The estimated values of the parameters for the two clinical endpoints are D (50) = 70.2 Gy, gamma = 1.22, s = 0.35 for fecal leakage and D (50) = 74.0 Gy, gamma = 0.75, s approximately 0 for blood or phlegm in stools. The standard deviations of the parameters were also calculated together with the confidence intervals of the dose-response curves. The analysis proved that the treatment outcome pattern of the patient material can suitably be reproduced by the relative seriality model (probability of finding a worse fit = 60.2%, the area under the receiver operating characteristic curve = 0.72 and 0.69 and chi(2)-test = 0.97 and 0.86, respectively). CONCLUSION: : Fecal leakage is characterized by a medium relative seriality whereas blood or phlegm in stools was found to have strong volume dependence (low relative seriality). Diminishing the biologically effective uniform dose to anal sphincter < 40-45 Gy may significantly reduce the risk of fecal leakage or blood or phlegm in stools for patients irradiated for prostate cancer.
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
