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| 2. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 5. |
- Laikre, Linda, et al.
(författare)
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Effekter av spridning av genetiskt främmande populationer : En kartläggning av förutsättningarna för uppföljande studier av utsättningar av djur och växter i Sverige
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Förord Spridning av främmande arter utgör ett av de stora hoten mot biologisk mångfald. En viktig del i arbetet med att verkställa Förenta nationernas konvention om biologisk mångfald (Convention on Biological Diversity – CBD) är därför att öka kunskapen kring, och förhindra fortsatt spridning av, sådana arter. Begreppet ”art” har en vid definition inom konventionsarbetet – även lägre taxonomiska enheter så som underarter och genetiskt särpräglade populationer omfattas. Spridning av genetiskt främmande populationer utgör alltså ett internationellt erkänt hot mot biologisk mångfald. Framför allt är det diversiteten på gennivå som kan drabbas negativt av sådan spridning. Vetenskapliga rådet för biologisk mångfald utses av Sveriges regering och ska bistå regeringen med råd i samband med internationellt och nationellt arbete med frågor som rör biologisk mångfald. Rådet har länge påtalat vikten av att öka kunskapen kring den genetiska nivån av biologisk mångfald och inte minst effekterna på denna mångfald av storskaliga utsättningar av genetiskt främmande populationer. Sådana utsättningar är vanliga inom skogsbruket, fiskevården och viltvården. Från min egen mångåriga erfarenhet av fiskevårdsfrågor har jag praktisk erfarenhet av att introduktion och spridning av främmande arter och populationer kan få högst påtagliga negativa konsekvenser.Vetenskapliga rådet för biologisk mångfald har i samband med konventionens tillämpning tagit upp frågor med koppling till den genetiska variationens betydelse – särskilt de vetenskapliga aspekterna kring detta. Rådet har också arrangerat en workshop som för första gången samlade experter och intressenter från de tre områden inom vilka storskaliga utsättningar bedrivs (skogsbruket, fisk- och viltvården). De intressanta och givande diskussionerna finns refererade i Rapport 5683 i Naturvårdsverkets serie. I den nu föreliggande rapporten fortsätter kartläggningen av vad vi egentligen vet om de storskaliga utsättningarna i Sverige och vilka effekter de har på biologisk mångfald. Ett gediget arbete har gjorts för att försöka bringa reda i detta område där dokumentation till stora delar saknas. Bristen på registrering och uppföljning av dessa stora spridningar, som riskerar att förändra den genetiska sammansättning som under årtusenden mejslats fram hos våra vilda fisk-, träd- och fågelpopulationer, är skrämmande. Här behövs en snabb och påtaglig förändring. Vetenskapliga rådet för biologisk mångfald kommer att fortsätta ägna denna fråga stor uppmärksamhet. Det är angeläget att Sverige bedriver ett starkt och engagerat arbete som ligger i internationell framkant när det gäller att slå vakt om den grundläggande, och för fortsatt evolution nödvändiga, mångfalden på gennivå. Stockholm den 10 september 2008 Per Wramner Professor i tillämpad miljövetenskap Ordförande för Vetenskapliga rådet för biologisk mångfald Förord 2 Utsättning av främmande populationer eller provenienser av växter och djur sker i stor skala i svenska marker och vattendrag. Spridningen av främmande populationer har stora ekonomiska värden men vi vet väldigt lite om vilka effekter den har på biologisk mångfald. Etablering av främmande genotyper kan leda till förlust och förändringar av, i första hand, mångfalden på gennivå hos mottagande naturliga populationer. I förlängningen kan sådana effekter även drabba art- och ekosystemnivåerna negativt. Det är mycket angeläget att öka kunskaperna inom detta område. Regeringen har uppdragit åt naturvårdsverket att ta fram en nationell strategi och handlingsplan för främmande arter och genotyper. Denna rapport utgör ett underlag i detta arbete. Uppdraget gavs med anledning av uppföljningen av miljökvalitetsmålen och implementering av artikel 8 h i Konventionen om biologisk mångfald som särskilt berör främmande arter och populationer och deras effekter på biologisk mångfalden. Rapporten utgör en uppföljning av den första kartläggningen av spridning av genetiskt främmande populationer inom fiske- och viltvården samt skogsbruk i Sverige som genomfördes under 2004–2005. Syftet med rapporten är en fördjupad granskning av den information som är möjlig att få fram när det gäller spridningen av främmande populationer eller genotyper i Sverige, samt i vilken utsträckning effekterna av sådana utsättningar kan kartläggas. Författarna är ensamma ansvariga för rapportens innehåll.Stockholm den 7 oktober 2008Naturvårdsverket
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| 6. |
- Laikre, Linda, et al.
(författare)
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Potentials for monitoring gene level biodiversity : using Sweden as an example
- 2008
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Ingår i: Biodiversity and Conservation. - : Springer Science and Business Media LLC. - 0960-3115 .- 1572-9710. ; 17:4, s. 893-910
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Tidskriftsartikel (refereegranskat)abstract
- Programs for monitoring biological diversity over time are needed to detect changes that can constitute threats to biological resources. The convention on biological diversity regards effective monitoring as necessary to halt the ongoing erosion of biological variation, and such programs at the ecosystem and species levels are enforced in several countries. However, at the level of genetic biodiversity, little has been accomplished, and monitoring programs need to be developed. We define “conservation genetic monitoring” to imply the systematic, temporal study of genetic variation within particular species/populations with the aim to detect changes that indicate compromise or loss of such diversity. We also (i) identify basic starting points for conservation genetic monitoring, (ii) review the availability of such information using Sweden as an example, (iii) suggest categories of species for pilot monitoring programs, and (iv) identify some scientific and logistic issues that need to be addressed in the context of conservation genetic monitoring. We suggest that such programs are particularly warranted for species subject to large scale enhancement and harvest—operations that are known to potentially alter the genetic composition and reduce the variability of populations.
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| 9. |
- Larsson, Lena C., 1965-
(författare)
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Disentangling small genetic differences in large Atlantic herring populations: comparing genetic markers and statistical power
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genes are the foundation of evolution and biodiversity. The genetic structure of natural populations needs to be understood to maintain exploited resources rationally. This thesis focuses on genetic variability and methods to determine spatial and temporal genetic heterogeneities. Intense human exploitation generates particular challenges to conserve genetic diversity of fishes since it has genetic effects. My research concerns one of our most valuable fish species: the Atlantic herring (Clupea harengus).I analyzed Atlantic herring samples from the North and Baltic Seas. The objectives were to determine: 1) spatial genetic structure, 2) whether allozymes and microsatellites provide similar descriptions of the differentiation pattern, or 3) if they are influenced by selection, 4) factors affecting statistical power when testing for genetic differentiation, and 5) the temporal stability of the genetic structure.The results show: 1) very low levels of spatial genetic differentiation in Atlantic herring; a major component is a difference between the Baltic and North Seas, 2) a concordant pattern with allozymes and microsatellites, 3) that selection influences a microsatellite locus, which can be a low salinity adaptation, 4) that statistical power is substantial for frequently used sample sizes and markers; the difference in power between organelle and nuclear loci is partly dependent on the populations’ stage of divergence, and 5) no changes in amount of genetic variation or spatial genetic structure over a 24-year period; the selection pattern in one microsatellite locus remained.The notion that the large population sizes make herring unlikely to lose genetic diversity may be disputed. I found small local effective population sizes, and the evidence of selection hints of a distinct evolutionary lineage in the Baltic. When Atlantic herring is managed as very large units, there can be detrimental genetic effects if certain population segments are excessively harvested.
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| 10. |
- Larsson, Lena C., et al.
(författare)
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Statistical power for detecting genetic divergence–organelle versus nuclear markers
- 2009
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 10:5, s. 1255-1264
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Tidskriftsartikel (refereegranskat)abstract
- Statistical power is critical in conservation for detecting genetic differences in space or time from allele frequency data. Organelle and nuclear genetic markers have fundamentally different transmission dynamics; the potential effect of these differences on power to detect divergence have been speculated on but not investigated. We examine, analytically and with computer simulations, the relative performance of organelle and nuclear markers under basic, ideal situations. We conclude that claims of a generally higher resolving power of either marker type are not correct. The ratio R = FST,organelle/FST,nuclear varies between 1 and 4 during differentiation and this greatly affects the power relationship. When nuclear FST is associated with organelle differentiation four times higher, the power of the organelle marker is similar to two nuclear loci with the same allele frequency distribution. With large sample sizes (n C 50) and several populations or many alleles per locus (C5), the power difference may typically be disregarded when nuclear FST[0.05. To correctly interpret observed patterns of genetic differentiation in practical situations, the expected FSTs and the statistical properties (i.e., power analysis) of the genetic markers used should be evaluated, taking the observed allele frequency distributions into consideration.
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| 12. |
- Sjöström, Lars, et al.
(författare)
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Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial.
- 2009
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Ingår i: The lancet oncology. - 1474-5488. ; 10:7, s. 653-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. METHODS: The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years). FINDINGS: Bariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. INTERPRETATION: Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. FUNDING: Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.
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| 13. |
- Sjöström, Lars, et al.
(författare)
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Effects of bariatric surgery on mortality in Swedish obese subjects.
- 2007
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Ingår i: The New England journal of medicine. - 1533-4406. ; 357:8, s. 741-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. METHODS: The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). RESULTS: The average weight change in control subjects was less than +/-2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29). CONCLUSIONS: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
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| 14. |
- Sundelöf, Johan, et al.
(författare)
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Serum cystatin C and the risk of Alzheimer disease in elderly men
- 2008
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 71:14, s. 1072-1079
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.
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