| 1. |
- Bill-Axelson, Anna, et al.
(author)
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Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
- 2018
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In: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
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Journal article (peer-reviewed)abstract
- BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
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| 2. |
- Hyttinen, O., et al.
(author)
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Deglaciation dynamics of the Fennoscandian Ice Sheet in the Kattegat, the gateway between the North Sea and the Baltic Sea Basin
- 2021
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In: Boreas. - : John Wiley & Sons. - 0300-9483 .- 1502-3885. ; 50:2, s. 351-368
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Journal article (peer-reviewed)abstract
- This paper presents an age–depth model based on an ultra-high-resolution, 80-m-thick sedimentary succession from a marine continental shelf basin, the Kattegat. This is an area of dynamic deglaciation of the Fennoscandian Ice Sheet during the Late Pleistocene. The Kattegat is also a transitional area between the saline North Sea and the brackish Baltic Sea. As such, it records general development of currents and exchange between these two systems. Data for the succession were provided through the Integrated Ocean Drilling Program Site M0060. The site indicates onset of deglaciation at c. 18 ka BP and relatively continuous sedimentation until 13 ka BP. At this point, sediments record a hiatus until c. 9–7 ka BP. The uppermost sedimentary unit contains redeposited material, but it is estimated to represent only the last c. 9–7 ka BP. The age–depth model is based on 17 select, radiocarbon-dated samples and is integrated with a set of physical and chemical proxies. The integrated records provide novel constraints on the timing of major palaeoenvironmental changes, such as the transition from glaciomarine proximal to glaciomarine distal and marine conditions, and their connections to known major events and processes in the region and the North Atlantic. Depositional evidence specifically documents connections between the Fennoscandian Ice Sheet behaviour and atmospheric and oceanic warming. Glacial retreat may have also depended on topographic factors such as changes in basin width and depth, linked to relative sea level changes and land uplift. The results indicate an early response of the Fennoscandian Ice Sheet to changing climate, and the ice sheet's possible influence on oceanic circulation during the Late Pleistocene deglaciation.
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| 3. |
- Hyttinen, O., et al.
(author)
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Holocene stratigraphy of the Ångermanälven River estuary, Bothnian Sea
- 2017
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In: Geo-Marine Letters. - : Springer. - 0276-0460 .- 1432-1157. ; 37:3, s. 273-288
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Journal article (peer-reviewed)abstract
- This study explores the Holocene depositional succession at the IODP Expedition 347 sites M0061 and M0062 in the vicinity of the Ångermanälven River estuary in the Bothnian Sea sector of the Baltic Sea in northern Scandinavia. Site M0061 is located in a coastal offshore setting (87.9 m water depth), whereas site M0062 is fully estuarine (69.3 m water depth). The dataset comprises acoustic profiles and sediment cores collected in 2007 and late 2013 respectively. Three acoustic units (AUs) were recognized. Lowermost AU1 is interpreted as a poorly to discontinuous stratified glaciofluvial deposit, AU2 as a stratified conformable drape of glaciolacustrine origin, and AU3 as a poorly stratified to stratified mud drift. A strong truncating reflector separates AU2 and AU3. Three lithological units (LUs) were defined in the sediment cores. LU1 consists of glaciofluvial sand and silt gradating into LU2, which consists of glaciolacustrine varves. A sharp contact interpreted as a major unconformity separates LU2 from the overlying LU3 (brackish-water mud). In the basal part of LU3, one debrite (site M0061) or two debrites (site M0062) were recognized. Information yielded from sediment physical properties (magnetic susceptibility, natural gamma ray, dry bulk density), geochemistry (total carbon, total organic carbon, total inorganic carbon and nitrogen), and grain size support the LU division. The depositional succession was formally subdivided into two alloformations: the Utansjö Alloformation and overlying Hemsön Alloformation; the Utansjö Alloformation was further subdivided into two lithostratigraphic formations: the Storfjärden and Åbordsön formations. The Storfjärden (sandy outwash) and Åbordsön (glaciolacustrine rhythmite) formations represent a glacial retreat systems tract, which started at ca. 10.6 kyr BP. Their deposition was mainly controlled by meltwater from the retreating ice margin, glacio-isostatic land uplift and the regressive (glacial) lake level. The Hemsön Alloformation (organic-rich brackish-water mud) represents a period of forced regression, starting possibly at ca. 9.5 kyr BP. At about 7 kyr BP, brackish water reached the study area as a result of the mid-Holocene marine flooding of the Baltic Sea Basin, but the rapid land uplift soon surpassed the associated (Littorina) transgression. Changed near-bottom current patterns, caused by the establishment of a permanent halocline, and the reduced sediment consistency caused by increased organic deposition resulted in a sharp and erosional base of the brackish-water mud. Estuarine processes and salinity stratification at site M0062 started to play a more important role. This study applies a combined allostratigraphic and lithostratigraphic approach over the conventional Baltic Sea stages. This approach makes it more straightforward to study this Baltic Sea deglaciation–postglacial sequence and compare it to other formerly glaciated shallow sea estuaries.
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| 4. |
- Lind, Lars, et al.
(author)
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Left ventricular hypertrophy in hypertension is associated with the insulin resistance metabolic syndrome
- 1995
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In: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 13:4, s. 433-438
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether left ventricular hypertrophy is associated with the insulin resistance syndrome. METHODS: Fifty patients with untreated hypertension were evaluated by recording office blood pressure during regular antihypertensive treatment and 24-h ambulatory blood pressure and office blood pressure after 4-6 weeks on placebo, echocardiography with M-mode measurements of left ventricular wall thickness and pulsed-wave Doppler measurements of mitral flow in diastole and the hyperinsulinaemic euglycaemic clamp, for determination of insulin sensitivity. RESULTS: The left ventricular wall thickness was found to be significantly related to blood pressure [r = 0.44, P < 0.004 for 24-h ambulatory systolic blood pressure (SBP)], fasting insulin level (r = 0.32, P < 0.03) and haematocrit level (r = 0.37, P < 0.009) and inversely related to insulin sensitivity (r = -0.59, P < 0.0001). Multiple regression analysis with these relationships together with confounding factors age, sex, body mass index and waist: hip ratio as independent variables showed insulin sensitivity to be the only significant variable, explaining 43% of the variation in left ventricular wall thickness, whereas 24-h ambulatory SBP explained a further 7%. Left ventricular diastolic filling, as evaluated by the mitral Doppler early: atrial ratio, was significantly correlated with insulin sensitivity (r = 0.42, P < 0.003) and inversely related to blood pressure (r = -0.41, P < 0.02 for 24-h ambulatory SBP), left ventricular wall thickness (r = -0.34, P < 0.02) and serum fibrinogen level (r = -0.63, P < 0.0001). However, multiple regression analysis showed that insulin sensitivity was more closely related to diastolic filling than to blood pressure or left ventricular wall thickness. CONCLUSION: The present study showed left ventricular wall thickness to be closely associated with insulin resistance. Because diastolic dysfunction of the left ventricle was also related to a decreased insulin sensitivity, these findings suggest that left ventricular hypertrophy and diastolic dysfunction are associated with the insulin resistance metabolic syndrome.
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| 5. |
- Obrochta, S. P., et al.
(author)
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The undatables : Quantifying uncertainty in a highly expanded Late Glacial-Holocene sediment sequence recovered from the deepest Baltic Sea basin—IODP Site M0063
- 2017
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In: Geochemistry Geophysics Geosystems. - : American Geophysical Union (AGU). - 1525-2027. ; 18:3, s. 858-871
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Journal article (peer-reviewed)abstract
- Laminated, organic-rich silts and clays with high dissolved gas content characterize sediments at IODP Site M0063 in the Landsort Deep, which at 459 m is the deepest basin in the Baltic Sea. Cores recovered from Hole M0063A experienced significant expansion as gas was released during the recovery process, resulting in high sediment loss. Therefore, during operations at subsequent holes, penetration was reduced to 2 m per 3.3 m core, permitting expansion into 1.3 m of initially empty liner. Fully filled liners were recovered from Holes B through E, indicating that the length of recovered intervals exceeded the penetrated distance by a factor of >1.5. A typical down-core logarithmic trend in gamma density profiles, with anomalously low-density values within the upper ∼1 m of each core, suggests that expansion primarily occurred in this upper interval. Thus, we suggest that a simple linear correction is inappropriate. This interpretation is supported by anisotropy of magnetic susceptibility data that indicate vertical stretching in the upper ∼1.5 m of expanded cores. Based on the mean gamma density profiles of cores from Holes M0063C and D, we obtain an expansion function that is used to adjust the depth of each core to conform to its known penetration. The variance in these profiles allows for quantification of uncertainty in the adjusted depth scale. Using a number of bulk 14C dates, we explore how the presence of multiple carbon source pathways leads to poorly constrained radiocarbon reservoir age variability that significantly affects age and sedimentation rate calculations.
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| 6. |
- Penney, K. L., et al.
(author)
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mRNA expression signature of Gleason grade predicts lethal prostate cancer
- 2011
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:17, s. 2391-2396
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Journal article (peer-reviewed)abstract
- PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
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| 7. |
- Sadr-Azodi, O., et al.
(author)
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Abdominal and Total Adiposity and The Risk of Acute Pancreatitis : A Population-Based Prospective Cohort Study
- 2013
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In: American Journal of Gastroenterology. - : NATURE PUBLISHING GROUP. - 0002-9270 .- 1572-0241. ; 108:1, s. 133-139
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Previous research has indicated that obesity may be linked to the severity of acute pancreatitis. However, the association between abdominal and total adiposity as risk factors in the development of acute pancreatitis in a general population has not been studied. METHODS: A follow-up study was conducted, using the Swedish Mammography Cohort and the Cohort of Swedish Men, to examine the association between waist circumference and body mass index (BMI) and the risk of first-time acute pancreatitis. Severe acute pancreatitis was defined as hospital stay of >14 days, in-hospital death, or mortality within 30 days of discharge. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% confidence intervals (CIs), adjusted for confounders. RESULTS: In total, 68,158 individuals, aged 46-84 years, were studied for a median of 12 years. During this time, 424 persons developed first-time acute pancreatitis. The risk of acute pancreatitis among those with a waist circumference of >105 cm was twofold increased (RR = 2.37; 95 % CI: 1.50-3.74) compared with individuals with a waist circumference of 75.1-85.0 cm, when adjusted for confounders. This association was seen in patients with non-gallstone-related and gallstone-related acute pancreatitis. The results remained unchanged when stratifying the analyses with regards to sex or the severity of acute pancreatitis. There was no association between BMI and the risk of acute pancreatitis. CONCLUSIONS: Abdominal adiposity, but not total adiposity, is an independent risk factor for the development of acute pancreatitis. Am J Gastroenterol 2013; 108:133-139; doi:10.1038/ajg.2012.381; published online 13 November 2012
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| 8. |
- Sadr-Azodi, O., et al.
(author)
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Cigarette smoking, smoking cessation and acute pancreatitis : a prospective population-based study
- 2012
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In: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288. ; 61:2, s. 262-267
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Journal article (peer-reviewed)abstract
- Background Several studies have shown that smoking increases the risk of chronic pancreatitis. However, the impact of smoking on the development of acute pancreatitis has not been fully studied. Objective To clarify the association between cigarette smoking, smoking cessation and the risk of acute pancreatitis. Design A follow-up study was conducted of 84 667 Swedish women and men, aged 46-84, during 12 years to study the association between smoking status, smoking intensity and duration, duration of smoking cessation and the risk of acute pancreatitis. Only those with the first event of the disease and no previous history of acute pancreatitis were included. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% CI for different smoking-related variables, adjusted for age, gender, body mass index, diabetes, educational level and alcohol consumption. Results In total, 307 cases with non-gallstone-related and 234 cases with gallstone-related acute pancreatitis were identified. The risk of non-gallstone-related acute pancreatitis was more than double (RR 2.29; 95% CI 1.63 to 3.22, p<0.01) among current smokers with >= 20 pack-years of smoking as compared with never-smokers. The corresponding risk among individuals with >= 400 g monthly consumption of alcohol was increased more than fourfold (RR=4.12; 95% CI 1.98 to 8.60, p<0.01). The duration of smoking rather than smoking intensity increased the risk of non-gallstone-related acute pancreatitis. After two decades of smoking cessation the risk of non-gallstone-related acute pancreatitis was reduced to a level comparable to that of non-smokers. There was no association between smoking and gallstone-related acute pancreatitis. Conclusion Smoking is an important risk factor for non-gallstone-related acute pancreatitis. Early smoking cessation should be recommended as a part of the clinical management of patients with acute pancreatitis.
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