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1.
  • Joshi, Peter K, et al. (författare)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • Tidskriftsartikel (refereegranskat)abstract
    • Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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3.
  • Andersson, Agneta, et al. (författare)
  • Costs of informal care for patients in advanced home care : a population based study
  • 2003
  • Ingår i: International Journal of Technology Assessment in Health Care. - 0266-4623 .- 1471-6348. ; 19:4, s. 656-663
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Several studies have sought to analyze the cost-effectiveness of advanced home care andhome rehabilitation. However, the costs of informal care are rarely included in economic appraisals ofhome care. This study estimates the cost of informal care for patients treated in advanced home careand analyses some patient characteristics that influence informal care costs.Methods: During one week in October 1995, data were collected on all 451 patients in advanced homecare in the Swedish county of O¨ stergo¨ tland. Costs were calculated by using two models: one includingleisure time, and one excluding leisure time. Multiple regression analysis was used to analyze factorsassociated with costs of informal care.Results: Seventy percent of the patients in the study had informal care around the clock during theweek investigated. The patients had, on average, five formal care visits per week, each of which lastedfor almost half an hour. Thus, the cost of informal care constituted a considerable part of the costof advanced home care. When the cost of leisure time was included, the cost of informal care wasestimated at SEK 5,880 per week per patient, or twice as high as total formal caregiver costs. Whenleisure time was excluded, the cost of informal care was estimated at SEK 3,410 per week per patient,which is still 1.2 times higher than formal caregiver costs (estimated at SEK 2,810 per week per patient).Informal care costs were higher among patients who were men, who were younger, who had their ownhousing, and who were diagnosed with cancer.Conclusions: Studies of advanced home care that exclude the cost of informal care substantiallyunderestimate the costs to society, regardless of whether or not the leisure time of the caregiver isincluded in the calculations.
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4.
  • Andersson, David, et al. (författare)
  • Co-morbidity and health care utilisation five years prior to diagnosis for depression : A register-based study in a Swedish population
  • 2011
  • Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 11, s. 552-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDepressive disorders have been associated with a number of co-morbidities, and we   hypothesized that patients with a depression diagnosis would be heavy users of health   care services, not only when first evaluated for depression, but also for preceding   years. The aim of this study was to investigate whether increased health care utilisation   and co-morbidity could be seen during five years prior to an initial diagnosis of   depression.MethodsWe used a longitudinal register-based study design. The setting comprised the general   population in the county of Östergötland, south-east Sweden. All 2470 patients who   were 20 years or older in 2006 and who received a new diagnosis of depression (F32   according to ICD-10) in 2006, were selected and followed back to the year 2001, five   years before their depression diagnosis. A control group was randomly selected among   those who were aged 20 years or over in 2006 and who had received no depression diagnosis   during the period 2001-2006.ResultsPredictors of a depression diagnosis were a high number of physician visits, female   gender, age below 60, age above 80 and a low socioeconomic status.Patients who received a diagnosis of depression used twice the amount of health care   (e.g. physician visits and hospital days) during the five year period prior to diagnosis   compared to the control group. A particularly strong increase in health care utilisation   was seen the last year before diagnosis. These findings were supported with a high   level of co-morbidity as for example musculoskeletal disorders during the whole five-year   period for patients with a depression diagnosis.ConclusionsPredictors of a depression diagnosis were a high number of physician visits, female   gender, age below 60, age above 80 and a low socioeconomic status. To find early signs   of depression in the clinical setting and to use a preventive strategy to handle these   patients is important.
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5.
  • Bladh, Marie (författare)
  • Birth Characteristics’ Impacton Future Reproduction and Morbidity Among Twins an dSingletons
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Globally, in both developed and developing countries, the twinning rates have increased since the early 70’s. A large proportion of twins are born preterm and/or small-for-gestational-age (SGA) and/or with a low birth weight. Several studies have been performed on the long-term effect of these non-optimal birth characteristics on future reproductive performance and morbidity. Yet, most studies exclude twins or higher order pregnancies and thus the findings are based on singleton pregnancies only.The aim of the present thesis was therefore to investigate the impact of non-optimal birth characteristics in terms of preterm birth, small-for-gestational age, and low birth weight, on the reproductive pattern and morbidity among twins and singletons Furthermore, the present thesis attempted to establish whether twins and singletons were affected in the same manner.The studies included in this thesis are prospective population-based register studies, including all men and women, alive and living in Sweden at age 13, who were born between 1973 and 1983 (1,000,037 singletons and 16,561 twins) for the first three studies with follow-up till the end of 2006 and 2009. The last study included all men and women, alive and living in Sweden at age 13, who were born between 1973 and 1993 (2,051,479 singletons and 39,726 twins) with follow-up till the end of 2012.In general, twins were found less likely to reproduce between 13 and 33 years of age compared with singletons. Stratifying data by different birth characteristics, it was found that twins had a lower likelihood of reproducing on several different birth characteristics (appropriate-for-gestational-age, normal birth weight, low birth weight, term birth, preterm birth). However, twins born very preterm had an increased likelihood of reproducing compared with singletons born very preterm.Not taking birth characteristics into account, twinning was associated with a higher degree of hospitalization. However, accounting for the diverging birth characteristics this difference diminished and for some diagnoses the relationship was reversed such that twins were actually less likely to be hospitalized compared with singletons.In terms of the heritability of non-optimal birth characteristics singleton mothers born preterm were more predisposed to give birth to a child that was preterm while singleton mothers born SGA more often gave birth to a child either born preterm or SGA. Among twins this heritability was not as evident. The only difference observed was among twin mothers born SGA who were more likely to give birth to a child born SGA.In the extended cohort comprising those born between 1973 and 1993, male and female twins were found to be less likely to become parents compared with singletons. No difference was found among women in terms of having a second child, while male twins were more likely to have a second child compared with male singletons. It was also found that the likelihood of becoming a first-time parent and second-time parent was positively associated with the number of siblings.
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6.
  • Bladh, Marie, et al. (författare)
  • Hospitalization in Adolescence and Young Adulthood Among Twins and Singletons : A Swedish Cohort Study of Subjects Born Between 1973 and 1983
  • 2013
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 16:3, s. 707-715
  • Tidskriftsartikel (refereegranskat)abstract
    • Children born with non-optimal birth characteristics — that is, are small for gestational age and/or preterm — have an increased risk for several long-term effects such as neurological sequelae and chronic disease. The purpose of this study was to examine whether twins exhibited a different outcome, compared with singletons, in terms of hospitalization during adolescence and early adulthood, and to what extent differences remain when considering the divergence in birth characteristics between singletons and twins. Persons born between 1973 and 1983 in Sweden and surviving until age 13 were included and followed until the end of 2006. Data on birth characteristics, parental socio-demographic factors, and hospitalizations were collected from national registers. Adjusting for parental socio-demographic factors, twins had a higher risk of being hospitalized than singletons (odds ratio, OR = 1.17, 95% confidence interval, CI = 1.10–1.25) and more often due to ‘Congenital anomalies’ (OR = 1.18, 95% CI = 1.06–1.28), ‘Infections’ (OR = 1.14; 95% CI = 1.08–1.20), ‘External causes of illness’ (OR = 1.10, 95% CI = 1.06–1.15), and ‘Diseases of the nervous system’ (OR = 1.18, 95% CI = 1.10–1.26). Stratifying for birth characteristics, this difference diminishes, and for some diagnoses non-optimal twins seem to do slightly better than non-optimal singletons. Thus, twins with non-optimal birth characteristics had a lower risk of hospitalization than non-optimal singletons on, for example, ‘Congenital anomalies’ and ‘Diseases of the nervous system’ (OR = 0.86, 95% CI = 0.77–0.96; OR = 0.88, 95% CI = 0.81–0.97, respectively) and Total (any) hospitalization (OR = 0.87, 95% CI = 0.83–0.92). Among those with optimal birth characteristics, twins had an increased hospitalization due to ‘External causes of illness’ (OR = 1.07, 95% CI = 1.02–1.13) compared with optimal singletons. Twins have higher hospitalization rates than singletons. In stratifying for birth characteristics, this difference diminishes, and for some diagnoses, non-optimal twins seem to do less poorly than non-optimal singletons.
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7.
  • Bladh, Marie, et al. (författare)
  • Intergenerational cohort study of preterm and small-for-gestational-age birth in twins and singletons
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 581-590
  • Tidskriftsartikel (refereegranskat)abstract
    • To date several studies have investigated the intergenerational effect of preterm and small-for-gestational-age births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and small for gestational age (SGA) among twins and singletons.A prospective population based register study of mother-first-born offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4073 twins and 264,794 singletons born in 1973-1983 and their firstborns born in 1986-2009. Preterm birth was defined as birth <37 weeks of gestation and SGA as < 2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers and mother’s socio-demographic factors in addition to maternal birth- characteristics.Among mothers born as singletons, being born preterm was associated with an increased risk for delivering a preterm child (adjusted OR 1.39, 95% CI 1.29-1.50) while being born SGA increased the likelihood of a SGA child (adjusted OR 3.04, 95% CI 2.80-3.30) as well as a preterm child (adjusted OR 1.30, 95% CI 1.20-1.40). In twin mothers, the corresponding ORs tended to be lower and the only statistically significant association was between a SGA mother and a SGA child (adjusted OR 2.15, 95% CI 1.40-3.31). A statistically significant interaction between twinning and mother’s size for gestational was identified in a multivariate linear regression analysis indicating that singleton mothers born SGA were associated with a lower birth weight compared to mothers not born SGA.Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons.
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8.
  • Bladh, Marie, et al. (författare)
  • Reproductive pattern among twins and singletons in relation to number of siblings : a Swedish cohort study of individuals born between 1973 and 1993
  • 2015
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background Twinning has been shown to be associated with a reduced reproductive rate compared to singletons. This can partly be explained by the birth-characteristics pertaining to twinning as many twins are born preterm, with low birth weight or small for gestational age. However, the intergenerational reproductive rate may also be due to familial factors such as number of siblings.Methods This is a register-based study of all men and women born in Sweden between 1973 and 1993 who were living in Sweden at 13 years of age. Data on the study objects’ own births as well as their offspring, parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios for the likelihood of becoming a parent were estimated using Cox’s proportion hazard models. All models were adjusted for socio-demographic and birth characteristics.Results Adjusting for number of siblings, socio-demographic factors and birth characteristics, twinning was associated with a decreased likelihood of becoming a first-time parent, compared with singletons both for females (HR (95% CI)=0.90 (0.88-0.93) and males (HR (95% CI)=0.96 (0.93-0.99). Having 3 or more siblings increased the chance of becoming a first-time parent among both male twins (HR (95% CI)=1.17 (1.08-1.27)) and singletons (HR (95% CI)=1.16 (1.15-1.18)) compared to having fewer than 3 siblings. This increased likelihood of becoming a parent was also present among female twins (HR (95% CI)=1.18 (1.10-1.26)) and singletons (HR (95% CI)=1.22 (1.21-1.24)).Conclusions Twins have a decreased likelihood of becoming a parent compared to singletons even when adjusting for number of siblings.
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9.
  • Bladh, Marie, et al. (författare)
  • Reproductive patterns among twins : a Swedish register study of men and women born 1973-1983
  • 2013
  • Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDuring the last decades there has been a steady increase of twin births. A combination of improved medical treatment of preterm and small-for-gestational age children has contributed to a higher number of surviving twins. Prematurity is known to affect reproduction in a negative way. Few studies have focused on the potential effect twinning may have on future reproduction. Thus, the aim of this study was to investigate the effect of being born a twin compared to being born a singleton have on future reproduction.MethodsIn a national population-based register study, all individuals born between 1973–1983 who were alive and living in Sweden at 13 years of age (n = 1 016 908) constituted the sample. Data on each study subject’s own birth as well as the birth of their first offspring, and parental socio-demographic factors were collected from Swedish population based registers. Hazard ratios and corresponding 95% CI was calculated using Cox proportional hazards model.ResultsTwins, both men and women, had a reduced likelihood of reproducing compared to singletons (women: HR = 0.89, 95% CI = 0.86-0.93; men: HR = 0.92, 95% CI = 0.87-0.97). This difference in birth rates can only partly be explained by diverging birth characteristics. Amongst men and women born very preterm, twins had an increased likelihood of reproducing compared to singletons (women: HR = 1.25, 95% CI = 1.02-1.62; men: HR = 1.34, 95% CI = 1.01-1.78).ConclusionsTwins have lower reproduction rates compared to singletons, which only to a certain degree can be explained by diverging birth characteristics.
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10.
  • Borg, Karin, 1972- (författare)
  • Sickness Absence with Musculoskeletal Diagnoses : An Eleven-Year Follow-Up of Young Persons
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: In Sweden, as well as in most Western countries, sickness absence is a major public health problem that has increased in recent years. This is a complex phenomenon related not only to ill health factors, but also to other factors on the levels of the individual, the family, the workplace, and the society. Most studies of sickness absence are cross sectional, which makes it difficult to investigate aetiological factors. A longitudinal study design is preferable, because sick-leave spells can have a long duration and are often due to chronic or recurrent disorders.Objectives: The aim of the present research was to conduct a pilot study to gain further information about factors associated with sickness absence and disability pension, perceptions of contacts with rehabilitation professionals, and self-rated health over time among younger persons initially on sick leave with low-back, neck, or shoulder diagnoses.Material and methods: An eleven-year prospective cohort study of all individuals who, in 1985, were aged 25–34 years, lived in the municipality of Linköping, Sweden, and had a sick-leave spell ≥ 28 days with low-back, neck, or shoulder diagnoses (n = 213, 61% women). The following information was obtained from registers: number of sick-leave days and spells in 1982–1984; diagnosis and demographical data in 1985 (age, sex, occupation, citizenship, marital status, and income); data on each sick-leave period (date, full/part time), disability pension (date, diagnoses, temporary/permanent, full/part time); emigration (date), and death (date, cause) from 1985 to 1 September 1996. In 1996, a questionnaire was sent to members of the cohort (response rate 73%). Different measures were used to analyse sickness absence and disability pension over the eleven-year period, possible risk factors for disability pension were tested by Cox regression, and possible factors predicting future low levels of sickness absence were tested by logistic regression. Based on the questionnaire perceptions of encounters with rehabilitation professionals were analysed with factor analyses and linear regression, and the so called health-line (a method to collect data on self-rated health over time) was tested, and the results were compared with data on sickness absence and disability ension.Results: The members of the cohort turned out to be a high-risk group for disability pension. After 11 years, 26% of the women and 14% of the men had been granted such benefits, mainly due to musculoskeletal diagnoses, but also with psychiatric diagnoses for half of the men and 17% of the women. Full-time pension was granted more often to men than to women. The women had higher levels of sickness absence. An extended Cox regression model proved suitable for prediction of disability pension. Taking citizenship and long-term sickness absence into consideration, the women had a 1.9 times higher risk of being granted disability pension than the men. Predictors for future low levels of sickness absence were a history of low sickness absence, having a white-collar job, and being married. These associations were not discerned when a pathogenic approach was used, which implies that factors other than the opposite risk factor for disability pension are associated with future low sickness absence. Three dimensions of the individuals’ contacts with professionals were identified: supportive treatment, distant treatment, and empowering treatment.Women perceived both social insurance officers and health care professionals as more supportive than the men did. Contact with social insurance officers was experienced as more supportive and empowering by persons on disability pension than by those not receiving such benefits. Data collected using the health-line (i.e., self-rated health from 1985 to 1995) was correlated with data on annual mean number of sick-leave days and days on disability pension. No tendency to recall bias was noted.Conclusions: Additional research is needed to elucidate the situation of women on sick leave with low-back, neck, and shoulder diagnoses. Further testing and practical application of statistical and epidemiological models for analysing sickness absence and disability pension data should be carried out to ascertain the validity and usefulness of such models.
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11.
  • Bygren, Lars Olov, 1936-, et al. (författare)
  • Change in paternal grandmothers' early food supply influenced cardiovascular mortality of the female grandchildren
  • 2014
  • Ingår i: BMC Genetics. - : BioMed Central. - 1471-2156. ; 15, s. 12-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This study investigated whether large fluctuations in food availability during grandparents' early development influenced grandchildren's cardiovascular mortality. We reported earlier that changes in availability of food - from good to poor or from poor to good - during intrauterine development was followed by a double risk of sudden death as an adult, and that mortality rate can be associated with ancestors' childhood availability of food. We have now studied transgenerational responses (TGR) to sharp differences of harvest between two consecutive years' for ancestors of 317 people in Overkalix, Sweden. Results: The confidence intervals were very wide but we found a striking TGR. There was no response in cardiovascular mortality in the grandchild from sharp changes of early exposure, experienced by three of the four grandparents (maternal grandparents and paternal grandfathers). If, however, the paternal grandmother up to puberty lived through a sharp change in food supply from one year to next, her sons' daughters had an excess risk for cardiovascular mortality (HR 2.69, 95% confidence interval 1.05-6.92). Selection or learning and imitation are unlikely explanations. X-linked epigenetic inheritance via spermatozoa seemed to be plausible, with the transmission, limited to being through the father, possibly explained by the sex differences in meiosis. Conclusion: The shock of change in food availability seems to give specific transgenerational responses.
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12.
  • Carlsson, Britt-Marie, et al. (författare)
  • Availability of insulin pump therapy in clinical practice
  • 2012
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 29:8, s. 1055-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabet. Med. 29, 10551059 (2012) Aim To examine the availability of insulin pump therapy in patients with Type 1 diabetes. Methods Patients using insulin pumps among a cohort of 7224 patients with Type 1 diabetes were studied. Results In logistic regression, used to evaluate variables not changing over time among the total cohort, use of insulin pumps varied by outpatient clinic (P < 0.001) and sex (P < 0.001). Cox regression analysis in 5854 patients with detailed patient data prior to use of an insulin pump showed higher HbA1c (P < 0.0001), lower creatinine (P = 0.002), high and low insulin doses (P < 0.0001), younger age (P < 0.0001) and female sex (P < 0.0001) to be associated with use of an insulin pump. Women were 1.5-fold more likely to start using an insulin pump (hazard ratio 1.52, 95% confidence interval 1.291.79) and patients in the 20- to 30-years age range were more than twice as likely to begin use of an insulin pump than patients aged 4050 years (hazard ratio 8.63, 95% confidence interval 5.9112.59 and hazard ratio 3.98, 95% confidence interval 2.805.64, respectively). A 10-mu mol/l higher level of creatinine was associated with a hazard ratio of 0.56 (95% confidence interval 0.390.81) of starting use of an insulin pump. Conclusions At 10 hospital outpatient clinics in Sweden, use of insulin pumps therapy varied by clinic. A higher proportion of women began using insulin pumps. Younger patients and patients with fewer complications were also more likely to start using an insulin pump. Further research is needed to confirm these findings in other geographical regions and to understand whether the availability of insulin pumps today is optimized.
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13.
  • Carstensen, John, et al. (författare)
  • How does comorbidity influence healthcare costs? A population-based cross-sectional study of depression, back pain and osteoarthritis
  • 2012
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 2, s. e000809-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To analyse how comorbidity among patients with back pain, depression and osteoarthritis influences healthcare costs per patient. A special focus was made on the distribution of costs for primary healthcare compared with specialist care, hospital care and drugs.Design Population-based cross-sectional study.Setting The County of Östergötland, Sweden.Patients Data on diagnoses and healthcare costs for all 266 354 individuals between 20 and 75 years of age, who were residents of the County of Östergötland, Sweden, in the year 2006, were extracted from the local healthcare register and the national register of drug prescriptions.Main outcome measures The effects of comorbidity on healthcare costs were estimated as interactions in regression models that also included age, sex, number of other health conditions and education.Results The largest diagnosed group was back pain (11 178 patients) followed by depression (7412 patients) and osteoarthritis (5174 patients). The largest comorbidity subgroup was the combination of back pain and depression (772 patients), followed by the combination of back pain and osteoarthritis (527 patients) and the combination of depression and osteoarthritis (206 patients). For patients having both a depression diagnosis and a back pain diagnosis, there was a significant negative interaction effect on total healthcare costs. The average healthcare costs among patients with depression and back pain was SEK 11 806 lower for a patient with both diagnoses. In this comorbidity group, there were tendencies of a positive interaction for general practitioner visits and negative interactions for all other visits and hospital days. Small or no interactions at all were seen between depression diagnoses and osteoarthritis diagnoses.Conclusions A small increase in primary healthcare visits in comorbid back pain and depression patients was accompanied with a substantial reduction in total healthcare costs and in hospital costs. Our results can be of value in analysing the cost effects of comorbidity and how the coordination of primary and secondary care may have an impact on healthcare costs.
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14.
  • Cloern, James E., et al. (författare)
  • Human activities and climate variability drive fast-paced change across the world's estuarine-coastal ecosystems
  • 2016
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 22:2, s. 513-529
  • Forskningsöversikt (refereegranskat)abstract
    • Time series of environmental measurements are essential for detecting, measuring and understanding changes in the Earth system and its biological communities. Observational series have accumulated over the past 2-5 decades from measurements across the world's estuaries, bays, lagoons, inland seas and shelf waters influenced by runoff. We synthesize information contained in these time series to develop a global view of changes occurring in marine systems influenced by connectivity to land. Our review is organized around four themes: (i) human activities as drivers of change; (ii) variability of the climate system as a driver of change; (iii) successes, disappointments and challenges of managing change at the sea-land interface; and (iv) discoveries made from observations over time. Multidecadal time series reveal that many of the world's estuarine-coastal ecosystems are in a continuing state of change, and the pace of change is faster than we could have imagined a decade ago. Some have been transformed into novel ecosystems with habitats, biogeochemistry and biological communities outside the natural range of variability. Change takes many forms including linear and nonlinear trends, abrupt state changes and oscillations. The challenge of managing change is daunting in the coastal zone where diverse human pressures are concentrated and intersect with different responses to climate variability over land and over ocean basins. The pace of change in estuarine-coastal ecosystems will likely accelerate as the human population and economies continue to grow and as global climate change accelerates. Wise stewardship of the resources upon which we depend is critically dependent upon a continuing flow of information from observations to measure, understand and anticipate future changes along the world's coastlines.
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15.
  • Dearing, John A., et al. (författare)
  • Safe and just operating spaces for regional social-ecological systems
  • 2014
  • Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 28, s. 227-238
  • Tidskriftsartikel (refereegranskat)abstract
    • Humanity faces a major global challenge in achieving wellbeing for all, while simultaneously ensuring that the biophysical processes and ecosystem services that underpin wellbeing are exploited within scientifically informed boundaries of sustainability. We propose a framework for defining the safe and just operating space for humanity that integrates social wellbeing into the original planetary boundaries concept (Rockstrom et al., 2009a,b) for application at regional scales. We argue that such a framework can: (1) increase the policy impact of the boundaries concept as most governance takes place at the regional rather than planetary scale; (2) contribute to the understanding and dissemination of complexity thinking throughout governance and policy-making; (3) act as a powerful metaphor and communication tool for regional equity and sustainability. We demonstrate the approach in two rural Chinese localities where we define the safe and just operating space that lies between an environmental ceiling and a social foundation from analysis of time series drawn from monitored and palaeoecological data, and from social survey statistics respectively. Agricultural intensification has led to poverty reduction, though not eradicated it, but at the expense of environmental degradation. Currently, the environmental ceiling is exceeded for degraded water quality at both localities even though the least well-met social standards are for available piped water and sanitation. The conjunction of these social needs and environmental constraints around the issue of water access and quality illustrates the broader value of the safe and just operating space approach for sustainable development.
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16.
  • DeKeyser, Nicholas, et al. (författare)
  • Premature birth and low birthweight are associated with a lower rate of reproduction in adulthood: a Swedish population-based registry study
  • 2012
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP): Policy B1. - 0268-1161 .- 1460-2350. ; 27:4, s. 1170-1178
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate if individuals born with sub-optimal birth characteristics have reduced probability of reproducing in adulthood. less thanbrgreater than less thanbrgreater thanUsing population-based registries, the authors included 522 216 males and 494 692 females born between 1973 and 1983 and examined their reproductive status as of 2006. Outcome measure was the hazard ratio (HR) of reproducing. Adjustments were made for socio-economic factors. less thanbrgreater than less thanbrgreater thanMales and females born very premature displayed a reduced probability of reproducing [HR 0.78, 95 confidence interval (CI): 0.700.86 for males; HR 0.81, CI: 0.750.88 for females]. Likewise for very low birthweight (HR 0.83, CI: 0.710.95 for males; HR 0.80, 95 CI: 0.720.89 for females). Individuals born large for gestational age (LGA) displayed no significant changes. Males born small for gestational age (SGA) had a 9 lower reproductive rate (CI: 0.890.94) and that reduction increased as the individuals aged. Women born SGA tended to start reproducing at an earlier age. less thanbrgreater than less thanbrgreater thanThe results suggest that being born with low birthweight, premature or SGA (for males) is associated with a reduced probability of reproducing as an adult. LGA shows no statistically significant relationship with future reproduction.
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17.
  • Edell-Gustafsson, Ulla, 1947-, et al. (författare)
  • Hyperarousal, depression and quality of life - Validity and reliability of the Swedish version of the Hyperarousal Scale
  • 2006
  • Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 20:1, s. 58-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Research focusing on hyperarousability in association with general sensitivity to stress has increased. This study aimed to: (i) describe values for self-reported hyperarousal behaviour traits, depression, sleeplessness behaviour and health-related quality of life [The Short Form 36 Health Survey Questionnaire (SF-36)] in a gender-stratified random sample from the Swedish population, and (ii) test the validity and reliability of the Swedish version of the Hyperarousal Behavioural Trait Scale (H-scale). Methods: In this study, 402 women and 391 men from Sweden were included. A test-retest study was performed on 297 subjects. Results: The total mean score on the H-scale was 29.5 (SD 10.0, 95% CI 28.8-30.2). Compared to men, women scored higher on the H-scale (total score, sub-scales and many items), whereas no evidence of an age trend was seen. The H-scale has proven to be a valid and reliable scale. Pearson's correlation coefficient showed similar magnitude and direction between the H-scale and the Zung's Self-rating Depression Scale, as between the H-scale and the Vicious Cycle of Sleeplessness Behaviour Scale, Vitality, Mental Health and the Mental Component Summary index on the SF-36 respectively. The Cronbach's alpha for the H-scale was 0.84 and estimated stability test-retest point of time varies between 0.73 and 0.80. Conclusions: This study indicates gender differences in response style in association with altered health-related quality of life. The H-scale is a valid and reliable self-reported scale for measuring hyperarousal behavioural trait research outcome in clinical practice. © 2006 Nordic College of Caring Science.
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18.
  • Ekholm Selling, Katarina, 1976- (författare)
  • Birth-characteristics, hospitalisations, and childbearing : Epidemiological studies based on Swedish register data
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In the past decades there has been an improvement in the medical treatment of children born preterm or with reduced foetal growth. This has resulted in a much higher survival rate of these children, but also in a higher number of surviving children with chronic conditions. These changes have, in turn, increased interest in investigating the connection between birth-characteristics and outcomes in later life. The overall aim of the present thesis was to study the relations between birth-characteristics, subsequent hospitalisations, and childbearing by means of data available in Swedish population-based registries.The study population in this thesis consisted of women (and men in Paper III) born in 1973-75 according to the Medical Birth Register and the Total Population Register. Information available in other registries, such as the Hospital Discharge Register, was obtained by individual record linkage.In Paper I, 148,281 women, alive and living in Sweden at 13 years of age, were included. Of the women, 4.1% were born preterm and 5.4% were born small for gestational age, and approximately 30% of all women had given birth between 13 and 27 years of age. We found that reduced foetal growth and possibly preterm birth were related to the likelihood of giving birth during the study period. The intergenerational effects of preterm birth and reduced foetal growth were investigated in Paper II and the study population consisted of 38,720 mother-offspring pairs. An intergenerational effect of reduced foetal growth was found, and reduced foetal growth in the mother also increased the risk for preterm birth in the child.Paper III was concerned with 304,275 men and women living in Sweden at 13 years of age. Of these men and women, 30% were hospitalised during adolescence and early adulthood (i.e. between 12 and 23 years of age). We found that men and women born small for gestational age or preterm were more likely to be hospitalised, and that those born small for gestational age seemed to be more at risk compared to those born preterm. Finally, in Paper IV, the relation between hospitalisations during adolescence and the likelihood of giving birth was studied in 142,998 women living in Sweden at 20 years of age. We found that a majority of the causes of hospitalisation during adolescence were positively connected to the likelihood of giving birth between 20 and 27 years of age. The relations presented in Papers I-IV were evident although socio-economic characteristics were adjusted for.
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19.
  • Ekholm Selling, Katarina, et al. (författare)
  • Hospitalization in adolescence affects the likelihood of giving birth : a Swedish population-based register study.
  • 2009
  • Ingår i: Acta paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 98:3, s. 561-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To examine the effect of hospitalization during adolescence on the likelihood of giving birth.Methods: 142 998 women born in 1973-75 were followed with the help of the Swedish Medical Birth Register (MBR) and the Swedish Total Population Register (TPR) up until the end of 2000 with respect to their likelihood of giving birth. All analyses were adjusted for parental socio-economic characteristics and factors related to the studied women's own birth.Results: The likelihood of giving birth between 20 and 27 years of age was positively affected by hospitalization at least once during adolescence according to the Swedish Hospital Discharge Register (HDR); adjusted hazard ratio (HR) = 1.32, 95% confidence interval: 1.29-1.35. Women hospitalized due to genitourinary diseases, respiratory diseases, abdominal problems and abuse of alcohol and drugs were more likely to have given birth during the study period, while hospitalizations according to cerebral palsy and congenital malformations tended to decrease childbearing. Women hospitalized due to psychiatric diseases had an increase likelihood of given birth at 20-24 years but a reduced thereafter.Conclusion: A majority of the causes of hospitalization during adolescence increased the likelihood of giving birth between ages 20 to 27.
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20.
  • Ekholm Selling, Katarina, et al. (författare)
  • Hospitalizations in adolescence and early adulthood among Swedish men and women born preterm or small for gestational age
  • 2008
  • Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 19:1, s. 63-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm birth and reduced intrauterine growth appear to be related to morbidity in childhood and later adulthood. We studied whether the risk of all-cause hospitalization in adolescence and early adulthood differed between individuals who were born preterm or small for gestational age (SGA) compared with those bom at term and appropriate for gestational age. Methods: Using Swedish registries, we followed 304,275 men and women born in 1973-1975 for any hospitalizations occurring in 1987-1996. Preterm birth was defined as <37 weeks of gestation and SGA as babies smaller than 2 standard deviations below the mean weight for gestational length, according to Swedish standards. We created 3 mutually exclusive categories: "preterm" (<37 weeks and not SGA), "SGA" (SGA and not preterm), and "both preterm and SGA." The comparison group was all term births not SGA. Childhood socioeconomic characteristics were accounted for in the analyses. Results: The overall risk of hospitalization was higher for men and women bom SGA (adjusted odds ratio = 1.16; 95% confidence interval = 1.12-1.21), for those born preterm (1.06; 1.02-1.10), and for those born both preterm and SGA (1.42; 1.26-1.59). In addition to higher risks for previously reported adverse health outcomes, such as neurodevelopment sequelae and congenital anomalies, men and women born SGA or preterm were more likely to be hospitalized due to unspecified symptoms. SGA also appeared to be associated with genitourinary diseases and drug use. Conclusions: Men and women born SGA or preterm were at higher risk for hospitalization during adolescence and early adulthood, with men and women born SGA more at risk than those bom preterm.
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21.
  • Ekholm Selling, Katarina, et al. (författare)
  • Intergenerational effects of preterm birth and reduced intrauterine growth: A population-based study of Swedish mother-offspring pairs
  • 2006
  • Ingår i: British Journal of Obstetrics and Gynaecology. - : Wiley. - 0306-5456 .- 1365-215X .- 1470-0328 .- 1471-0528. ; 113:4, s. 430-440
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To estimate the intergenerational effects of preterm birth and reduced intrauterine growth. Design Population-based cohort study. Settings Mother–first-born offspring pairs recorded in the Swedish Medical Birth Registry. Population Children born before 2001 to 38 720 women born in 1973–75. Methods The relationships between the mother's and the child's birth characteristics were estimated using logistic regression analysis. Adjustments were made for smoking habits, body mass index (BMI), and current and childhood socio-economic conditions. Analyses were performed on all mother–offspring pairs and on the pairs for which information on neither of the included background variables was missing (n= 24 520). Main outcome measures Preterm birth (<37 weeks of gestation) and small for gestational age (SGA) (<−2 SD of the Swedish standard). Results Mothers who themselves had been born preterm were not significantly more likely to deliver their own children preterm, compared with those who had been born at term (adjusted OR 1.24, 95% CI 0.95–1.62). Also, preterm birth in the mothers did not influence the occurrence of SGA in the children. However, the odds ratio for giving birth to SGA and preterm children, respectively, was higher among SGA mothers (OR 2.68, 95% CI 2.11–3.41 and OR 1.30, 95% CI 1.05–1.61). Mothers whose intrauterine growth was moderately reduced but who did not meet the criterion of being born SGA were also at higher risk of giving birth to both preterm and SGA children, respectively. Conclusions The present study showed evidence of intergenerational effects of reduced intrauterine growth even when socio-economic factors as well as BMI and smoking were adjusted for. There was, however, no consistent intergenerational effect of preterm birth.
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22.
  • Ekholm (Selling), Katarina, et al. (författare)
  • The probability of giving birth among women who were born preterm or with impaired fetal growth: A Swedish population-based registry study
  • 2005
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 161:8, s. 725-733
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary aim of this study was to investigate whether women born prematurely or with impaired fetal growth have a reduced probability of giving birth. Using Swedish population-based registries, the authors identified 148,281 women born in 1973–1975 for follow-up until 2001. Of these women, 4.1% were born preterm and 0.32% very preterm, 0.29% were born with a very low birth weight, and 5.4% were small for gestational age. Outcome measures were the hazard ratios for giving birth during the study period. Adjustments were made for socioeconomic factors. Very-low-birth-weight women displayed a reduced probability of giving birth (hazard ratio = 0.74, 95% confidence interval: 0.60, 0.91), most apparent among women aged 25 or more years. There were also tendencies of reduced hazard ratios of giving birth among women born preterm or very preterm in this age interval. Women born small for gestational age (below –2 standard deviations) seemed to be more likely to have given birth (hazard ratio = 1.09, 95% confidence interval: 1.04, 1.14), but when a more extreme group of small-for-gestational-age women (below –3 standard deviations) was defined, the association was less evident (hazard ratio = 1.04, 95% confidence interval: 0.94, 1.16). The results suggest that very-low-birth-weight women and, possibly, women born preterm or very preterm have a reduced probability of giving birth, while the results regarding small for gestational age are less clear.
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23.
  • Emterling, Anna, et al. (författare)
  • Clinicopathological significance of Nup88 expression in patients with colorectal cancer
  • 2003
  • Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 64:4, s. 361-369
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The nucleoporin Nup88 is overexpressed in a series of human malignancies, however, its clinicopathological significance has not been studied. Our aims were to analyze Nup88 expression in normal mucosa, primary tumors and metastases from colorectal cancer patients and further to identify relationships of Nup88 expression with clinicopathological and other factors.Materials and Methods: Using immunohistochemistry, we investigated Nup88 expression in 198 primary colorectal tumors, 96 normal mucosa samples and 35 lymph node metastases.Results: The results showed that the intensity of Nup88 expression increased from the normal mucosa to the primary tumors (p < 0.0001) and tended to increase from the primary tumors to the metastases (p = 0.15). Both primary tumors and metastases presented stronger expression in the invasive margin and vascular-invaded areas. Nup88 expression was positively related to distal tumor location (p = 0.01), infiltrative growth pattern (p = 0.04) and higher proliferative activity (p = 0.04) and reversely to the grade of differentiation (p = 0.02) and apoptosis (p = 0.049). Strong expression of Nup88 predicted a worse outcome in the patients with distal tumors during the follow-up period of up to 3 years (p = 0.02).Conclusions: It seems that overexpression of Nup88 was involved in the tumorigenesis and aggressiveness of colorectal cancers, and Nup88 may be used as a prognostic factor in patients with distal tumors.
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24.
  • Enthoven, Paul, 1955-, et al. (författare)
  • Predictive factors for 1-year and 5-year outcome for disability in a working population of patients with low back pain treated in primary care
  • 2006
  • Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 122:1-2, s. 137-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Many patients seeking primary care for low back pain continue to report disability several years after their initial visit. The aims of this study were to assess the independent predictive value of a number of potential predictive factors for disability at the 1-year and 5-year follow-ups, and to examine whether prediction models were improved by replacing baseline health-state-related variables with corresponding variables after treatment. A further aim was to describe possible differences between those on sick leave, early retirement or disability pension, and those who were not. Baseline factors were age, gender, self-reported physical-activity-related and work-related factors, expectations of treatment, similar problems previously, duration of episode, more than one localization, sick leave, pain frequency, disability, and well-being. The study sample comprised 148 participants in a previous randomized trial who were eligible for sick-leave benefits. Multiple logistic regression was used to identify predictive factors. At the 5-year follow-up, 37% (n = 19/52) of the patients with disability were on sick leave or were receiving early retirement or disability pension. For those without disability the corresponding figure was 9% (n = 8/92). Being a woman, duration of the current episode, similar problems during the previous 5 years, exercise level before the current episode, pain frequency at baseline, and disability after treatment emerged as predictive factors for disability at the 5-year follow-up. Replacing baseline health-state-related measures with corresponding measures after the treatment period, and adding physical-activity-related and possibly work-related factors might improve the likelihood of predicting future disability.
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25.
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26.
  • Eriksson, Hanna, et al. (författare)
  • Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma : A nationwide population-based study in Sweden
  • 2013
  • Ingår i: European Journal of Cancer. - Oxford : Elsevier. - 0959-8049 .- 1879-0852. ; 49:12, s. 2705-2716
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.METHODS:We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.RESULTS:The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55years, patients with truncal tumours and during the first 5years after diagnosis.CONCLUSION:Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.
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27.
  • Felix, Janine F, et al. (författare)
  • Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
  • 2016
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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28.
  • Fenner, Merle Friederike, et al. (författare)
  • Effect of selective IK,ACh inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation
  • 2020
  • Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:16, s. 3778-3794
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction. Key Results: XAF-1407 potently and selectively inhibited Kir3.1/3.4 and Kir3.4/3.4, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia. Conclusion and Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.
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29.
  • Fohlin, Helena, et al. (författare)
  • Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer
  • 2013
  • Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:6, s. 1196-1204
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionAkt is a signalling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of v-akt murine thymoma viral oncogene homologue 1 (Akt1) and v-akt murine thymoma viral oncogene homologue 2 (Akt2) in oestrogen receptor positive (ER+) and oestrogen receptor negative (ER–) breast cancer with long-term follow-up.Material and methodsThe expression of Akt in tumour tissue was analysed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. The median follow-up time was 19 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox’s proportional hazards model.ResultsThe risk of distant recurrence was reduced for patients with ER+ tumours expressing Akt2 compared to patients with no Akt2 expression (HR = 0.49, 95% CI 0.29–0.82, p = 0.007). When adjusting for important clinical tumour characteristics and treatment, Akt2 was still an independent prognostic factor (HR = 0.38, 95% CI 0.21–0.68, p = 0.001) and the association remained long-term. The prognostic value of Akt2 increased with higher oestrogen receptor levels from no effect among patients with ER– tumours to 68% risk reduction for the group with high ER-levels (P for trend = 0.042). Akt1 showed no significant prognostic information.ConclusionOur results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumours and that this association remains long-term. The prognostic value of Akt2 increases with higher oestrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer.
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30.
  • Fohlin, Helena, 1979- (författare)
  • Long-term prognostic and predictive factors in hormone receptor positive breast cancer
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The breast cancer survival in Sweden is good (almost 90 % 5-year relative survival) and has increased over time. For women with hormone receptor negative tumors, most relapses occur within the first 5 years after diagnosis. Thereafter the recurrence risk decreases rapidly. For women with estrogen receptor positive (ER+) tumors the annual risk for late recurrences is 1 – 2 %, even after 5 years of endocrine therapy. This risk accumulates so that approximately 25 % of the patients that are recurrence-free after five years from diagnosis may experience a relapse within further 15 years of follow-up. The relatively high long-term risk calls for identification of prognostic and predictive markers with long-term effect. Though, the number of such markers with proven significance is limited. Of the clinical characteristics, only nodal status and to some extent tumor size and tumor grade have been shown to have long-term prognostic value. In this thesis, we propose long-term prognostic and predictive markers for breast cancer.In paper I, we suggest the protein v-akt murine thymoma viral oncogene homologue 2 (AKT2) as a long-term prognostic marker among patients with ER+ tumors. In our study, besides nodal status, AKT2 was the only factor with long-term prognostic value. This is in accordance with some other studies, though we also showed that the significance of AKT2 was limited to ER+ tumors and that the impact increased with higher ER expression.Approximately 75 – 85 % of the ER+ tumors are also progesterone receptor positive (PR+). ER+/progesterone receptor negative (PR-) tumors are considered to be more aggressive and patients with such tumors are often treated with chemotherapy. In this group, more specific subgroups for targeted therapy are needed.Whereas ER has long been established as a predictive factor regarding tamoxifen benefit, the role of PR has not been clarified to date. In paper II, we showed that PR status adds predictive value to ER considering the long-term benefit from tamoxifen.In paper III, we aimed to identify new prognostic markers among patients with ER+ tumors. Systemically untreated patients with ER+/PR- tumors and high expression of the Ras-related protein RAB6C (RAB6C) had reduced distant recurrence rate. Therefore, we suggest RAB6C as a candidate marker for subgroup division among patients with ER+/PR- tumors.According to the results from paper II, there might be subgroups of patients with ER+/PRtumors that do benefit from tamoxifen. The aim of paper IV was to identify such subgroups. Here, we suggest that patients with ER+/PR- tumors and low RAB6C expression do benefit from tamoxifen.The results from this thesis may encourage further studies for more specific subgroup divisions. Such studies may lead to changes in the management program, where some patients with ER+ tumors should receive prolonged or more intense treatment and others reduced treatment based on the pathological markers AKT2, PR and RAB6C. 
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31.
  • Fohlin, Helena, 1979-, et al. (författare)
  • Low RAB6C expression is a predictor of tamoxifen benefit in estrogen receptor-positive/progesterone receptor-negative breast cancer
  • 2020
  • Ingår i: Molecular and clinical oncology. - : SPANDIDOS PUBL LTD. - 2049-9450 .- 2049-9469. ; 12:5, s. 415-420
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the last few decades, improved and more individualized treatment has contributed to the increased survival rate of patients with breast cancer. However, certain patients may receive excessive treatment resulting in undesired side effects. In a previous study, it was demonstrated that systemically untreated patients with estrogen receptor (ER)-positive/progesterone receptor (PR)-negative tumors with high Ras-related protein Rab-6C (RAB6C) expression levels (RAB6C(+)) had prolonged distant recurrence-free survival compared with that of patients exhibiting low RAB6C (RAB6C(-))-expressing tumors. The aim of the present study was to investigate whether RAB6C predicts the effectiveness of tamoxifen treatment. The present study used a dataset comprising 486 female patients with ER+ tumors from a randomized study conducted by the Stockholm Breast Cancer Study Group between November 1976 and August 1990. The patients were considered as low-risk if their tumor size was <= 30 mm and their lymph node status was negative. Patients were followed up until distant recurrence, mortality or when 25 years after randomization was achieved, whichever occurred first. For patients with ER+/PR-/RAB6C(+) tumors, prolonged distant recurrence-free survival could not be observed if the patients were treated with tamoxifen [hazard ratio (HR), 1.82; 95% confidence interval (CI), 0.69-4.79; P=0.23], whereas patients with ER+/PR-/RAB6C(-) tumors had 75% reduced distant recurrence risk (HR, 0.25; 95% CI, 0.09-0.70; P=0.008). In the ER+/PR+ subgroup, patients with RAB6C(-) and RAB6C(+) tumors benefited from tamoxifen treatment, though it was most evident in the RAB6C(+) group (HR, 0.27; 95% CI, 0.13-0.58; P=0.001). The results of the present study indicated that, for patients with ER+/PR- tumors, those with low RAB6C expression benefited from tamoxifen treatment, whereas no benefit was observed in patients with high RAB6C levels.
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32.
  • Fohlin, Helena, 1979-, et al. (författare)
  • RAB6C is an independent prognostic factor of estrogen receptor-positive/progesterone receptor-negative breast cancer
  • 2020
  • Ingår i: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 19:1, s. 52-60
  • Tidskriftsartikel (refereegranskat)abstract
    • The majority of breast cancer tumors are estrogen receptor-positive (ER+) and can be treated with endocrine therapy. However, certain patients may exhibit a good prognosis without systemic treatment. The aim of the present study was to identify novel prognostic factors for patients with ER breast cancer tumors using gene copy data, and to investigate if these factors have prognostic value in subgroups categorized by progesterone receptor status (PR). Public data, including the whole genome gene copy data of 199 systemically untreated patients with ER+ tumors, were utilized in the present study. To assess prognostic value, patients were divided into two groups using the median gene copy number as a cut-off for the SNPs that were the most variable. One SNP was identified, which indicated that the Ras-related protein Rab-6C (RAB6C) gene may exhibit prognostic significance. Therefore, RAB6C protein expression was subsequently investigated in a second independent cohort, consisting of 469 systematically untreated patients (of which 310 were ER+) who received long term follow-up. In the public data set, a distant recurrence risk reduction of 55% was determined for copy numbers above the median value of RAB6C compared with numbers below [multivariable adjusted hazard ratio (HR), 0.45; 95% CI 0.28-0.72; P=0.001)]. It was also more pronounced in the ER+/PR- subgroup (HR, 0.15; 95% CI, 0.05-0.46; P=0.001). In the second cohort, patients of the ER+/PR- subgroup who exhibited high RAB6C expression had a reduced distant recurrence risk (HR, 0.17; 95% CI, 0.05-0.60; P=0.006). However, this was not identified among ER+/PR- tumors (HR, 1.31; 95% CI, 0.69-2.48; P=0.41). The results of the present study indicated that RAB6C serves as an independent prognostic factor of distant recurrence risk in systemically untreated patients with an ER+/PR- tumor.
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33.
  • Gao, Jingfang, 1966-, et al. (författare)
  • Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations
  • 2007
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 42:3, s. 345-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The inhibitory proteins, IκBs, regulate the activity of nuclear factor kappa-beta (NF-κB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IκBs may be involved in cancer development through the activation of NF-κB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3′ UTR of NFKBIA (encoding IκBα) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients. Material and methods. A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR-restriction fragment length polymorphism. Results. The frequency of the AG genotype was increased in the Chinese patients ≥50 years of age compared with the Chinese controls (odds ratio (OR) = 3.06, 95% confidence interval (CI) = 1.55-6.02, p=0.001), even when adjusted for age (OR = 3.20, 95% CI = 1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl = 1.28-7.60, p=0.01). Conclusions. Chinese individuals ≥50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients. © 2007 Taylor & Francis.
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34.
  • Gao, Jingfang, et al. (författare)
  • Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer
  • 2009
  • Ingår i: DIGESTIVE AND LIVER DISEASE. - : Elsevier BV. - 1590-8658. ; 41:2, s. 116-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose. The aim of this study was to get a deeper understanding into how adults with cerebral palsy (CP) experience physiotherapy and physical activity in a perspective from childhood to adulthood; and how personal and environmental factors influence possibilities for physiotherapy and physical activity. Method. Data was collected through interviews with 22 community-living adults (35-68 years) with CP, from five counties in Sweden. The questions were open-ended and the interviews were taped and transcribed to written language. The material was analysed through qualitative content analysis, a classification process resulting in different themes. Results. The narratives from the 22 informants, based on experiences from childhood to adulthood, resulted in a description of prerequisites for carrying out physiotherapy and physical activity. Five different themes were identified: (i) Being enjoyable, (ii) Giving effects, (iii) Being comprehensible, (iv) Being integrated in daily life, and (v) Supportive healthcare with competent professionals. Conclusion. The information from the interviews elucidates the importance of a lifelong support from healthcare professionals. Physiotherapists with attentiveness to different life situations in combination with good understanding and knowledge in CP could facilitate continuous physical activity in people growing up and ageing with CP.
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35.
  • Garvin, Peter, 1976-, et al. (författare)
  • Association between ambulatory saliva cortisol levels and plasma levels of matrix metalloproteinase-9 in a normal population
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Psychosocial strain has been demonstrated to be a risk factor for coronary artery disease (CAD) and also to be associated with a dysfunctional HPA-axis. Based on a proposal on cortisol resistance in maladaptive monocytes as a potential mechanism linking psychosocial strain with CAD, this study aimed at testing the association between levels of salivary cortisol and matrix metalloproteinase-9 (MMP-9) in a normal population. Methods: 359 participants (50 % women) aged 45-69 were enrolled to this study, randomly drawn from a normal population in Sweden. Saliva samples were collected thrice per day (at awakening, 30 minutes after awakening, and just before going to bed) during three consecutive days. Cortisol levels at awakening and 30 minutes after awakening were used to estimate the diurnal peak. Cortisol was analyzed using a radioimmunoassay method. MMP-9 was measured in plasma using an ELISA-method. Results: After adjustment for age and sex, significant trends regarding MMP-9 were found both for cortisol peak quintiles (beta +1.9 ng/mL per quintile, p=0.029) and cortisol evening values (beta +2.1 ng/ml per quintile, p=0.017). These findings were consistent in regressions either excluding participants with known diagnoses of myocardial infarction, angina pectoris, rheumatoid arthritis, diabetes, cancer with ongoing treatment, chronic obstructive lung disease, osteoporosis and hypothyroidism, or adjusting for these diseases, also after adjustment for cardiovascular risk factors. Conclusions: The associations found between cortisol levels and MMP-9 in a normal population hint at a potential pathway linking prolonged psychosocial strain with cardiovascular events.
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36.
  • Garvin, Peter, 1976-, et al. (författare)
  • Circulating Matrix Metalloproteinase-9 Is Associated with Cardiovascular Risk Factors in a Middle-Aged Normal Population
  • 2008
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:3, s. e1774-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9) have been demonstrated in patients with established coronary artery disease (CAD). The aim of this study was to analyse levels of MMP-9 in a population free from symptomatic CAD and investigate their associations with cardiovascular (CV) risk factors, including C-reactive protein (CRP). Methods: A cross-sectional study was performed in a population based random sample aged 45–69 (n = 345, 50% women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk factors were measured using questionnaires and standard laboratory methods.Results: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD 22.1 ng/mL). Among individuals without reported symptomatic CAD a positive association (p<0.001) was seen, for both men and women, of MMP-9 levels regarding total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia, diabetes, obesity, smoking, alcohol intake, physical activity and fruit and vegetable intake. The association was significant also after adjustment for CRP, and was not driven by a single risk factor alone. In regression models adjusted for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were independently positively associated with systolic blood pressure (p = 0.037), smoking (p<0.001), alcohol intake (p = 0.003) and CRP (p<0.001). The correlation coefficient between MMP-9 and CRP was r = 0.24 (p<0.001). Conclusions: In a population without reported symptomatic CAD, MMP-9 levels were associated with total CV risk load as well as with single risk factors. This was found also after adjustment for CRP 
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37.
  •  
38.
  • Garvin, Peter, et al. (författare)
  • Plasma Levels of Matrix Metalloproteinase-9 are Independently Associated With Psychosocial Factors in a Middle-Aged Normal Population
  • 2009
  • Ingår i: PSYCHOSOMATIC MEDICINE. - 0033-3174. ; 71:3, s. 292-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To test the association between psychosocial factors and circulating levels of matrix metalloproteinase-9 (MMP-9) in a normal population sample. Psychosocial factors have been associated with inflammatory markers and are of prognostic significance for coronary artery disease (CAD). The degrading enzyme MMP-9 is upregulated in inflammatory processes and hypothesized to play a role in the rupture of atherosclerotic plaques. Methods: A total of 402 participants (50% women), aged 45 to 69 years, were drawn randomly from a normal population. Psychosocial instruments covered depression (Center for Epidemiological Studies Depression Questionnaire, CES-D), vital exhaustion, hostile affect, cynicism, mastery, self-esteem, sense of coherence (SOC), emotional support, and social integration. Plasma MMP-9 was measured by an enzyme-linked immunosorbent assay method. Linear regression models were adjusted for age, sex, known CAD, rheumatoid arthritis, cancer, cardiovascular risk factors including C-reactive protein and ongoing medication. Results: After full adjustment, there were independent associations of elevated MMP-9 levels with CES-D (+2.9 ng/ml per SD, p=.02), hostile affect (+3.0 ng/ml per SD, p=.02), cynicism (+3.5 ng/ml per SD, p=.006), and SOC (-2.5 ng/ml per SD, p=.046). A principal component analysis extracted three components. The first was mainly extracted from CES-D, vital exhaustion, self-esteem, mastery, and SOC; the second was mainly extracted from hostile affect and cynicism. Both were independently associated with MMP-9 (p=.02, p=.04) when run in the same model. Conclusions: MMP-9 levels were associated with psychosocial factors in a middle-aged normal population sample, independently of traditional risk factors. The findings may constitute a possible link between psychosocial factors and cardiovascular risk.
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39.
  • Garvin, Peter, 1976- (författare)
  • Plasma levels of matrix metalloproteinase‐9 in a normal population : a psychoneuroendocrinological approach
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Several large‐scale epidemiological studies have demonstrated the prognostic significance of psychosocial factors and stress for coronary artery disease (CAD). Observations of sudden changes in CAD incidence have led to the proposal of mechanisms regarding atherosclerotic plaque vulnerability. The collagen‐degrading enzyme matrix metalloproteinase-9 (MMP-9) is increased in rupture‐prone plaques with high inflammatory activity, and circulating levels of MMP-9 are raised in patients with acute coronary syndrome. However, the distribution of MMP‐9 levels and its relations to psychosocial factors and the stress hormone cortisol have not been previously explored in a normal population.The aim of this dissertation was to examine in a normal population the association of circulating levels of MMP-9 with traditional cardiovascular risk factors including levels of C-reactive protein (CRP), with psychosocial factors, and with saliva levels of cortisol. In addition, the reliability of a new method of ambulatory saliva sampling for assessment of cortisol levels was evaluated. A sub‐sample of the Life conditions, Stress, and Health (LSH)-study, a population based study exploring psychoneuroendocrinological pathways mediating the differences in CAD incidence over socioeconomic status, was used. Plasma levels of MMP-9 were examined in a sample randomly drawn from the LSH‐study (n=400), aged 45 to 69 years at enrollment.The main findings were: 1) there was a positive association between plasma MMP-9 levels and total risk load of cardiovascular risk factors. The findings were persistent after adjusting for CRP and could not be attributed to a single risk factor. 2) After adjusting for traditional cardiovascular risk factors and CRP, MMP-9 levels were positively associated with psychosocial risk factors and negatively associated with psychosocial resources. 3) Pooling saliva samples prior to laboratory analysis were as reliable as arithmetic means for assessment of diurnal cortisol variation in a field research setting. 4) There was a positive association between circulating levels of MMP‐9 and saliva levels of cortisol, both diurnal peak level and evening level of cortisol. The observed associations between MMP‐9 and traditional cardiovascular risk factors, psychosocial factors, and saliva cortisol levels suggest a psychoneuroendocrinological pathway linking stress to plaque vulnerability and provide increased understanding of the association between psychosocial factors and CAD.
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40.
  • Garvin, Peter, 1976-, et al. (författare)
  • Pooling ambulatory saliva cortisol samples over consecutive days – as reliable as arithmetic means
  • 2008
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 68:6, s. 508-512
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: When cortisol measurements are to be studied in large populations, cost-effective analyses are needed. This study aimed at testing whether one pooled cortisol value over three consecutive days is as reliable as using the arithmetic mean of the samples from the same measure points. Material and methods: Thirty participants aged between 45 and 69 collected saliva in salivettes immediately after awakening (t1), 30 min after awakening (t2) and in the evening (t3) during 3 consecutive days. A fixed volume from each of the samples (t1, t2 and t3) was pooled prior to laboratory analysis. Mean levels over 3 days for t1, t2 and t3 were compared to corresponding levels of pooled vials. Cortisol levels were analysed using a radio immunoassay.Results: All measures tested had high correlations between mean values and pooled samples, exemplified with diurnal deviation rdif t2–t350.974 (CI 0.946;0.987), and awakening response rdif t2–t150.982 (CI 0.963;0.991). There were no statistical differences between the pooled values and the arithmetic means.Conclusion: Pooling samples gave as reliable results as arithmetic means did. Pooling samples prior to laboratory analysis is a cost-effective method for measuring general diurnal cortisol variation in field research projects.
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41.
  • Gnosa, Sebastian, et al. (författare)
  • AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy : a study in a Swedish clinical trial
  • 2014
  • Ingår i: British Journal of Cancer. - London, United Kingdom : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 111:1, s. 166-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.Methods: The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay. Results: The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P = 0.009) and worse disease-free survival (P = 0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.Conclusions: The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.
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42.
  • Gnosa, Sebastian, 1984- (författare)
  • Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The incidence and death rate for colorectal cancer (CRC) decreased during the last decades as a result of improved diagnosis and treatment. However, CRC is still the third most common cancer in the world, and is responsible for about 700 000 deaths per year worldwide. Therefore, it is important to understand the mechanisms of the disease, and to find molecular markers in order to further improve prognosis, and to develop new treatment strategies. Astrocyte elevated gene-1 (AEG-1), encoded by the MTDH gene, is upregulated in a variety of cancers. AEG-1 is involved in cell survival, proliferation, migration, invasion, metastasis,  angiogenesis, and apoptosis.The aim of this thesis was to investigate the role of AEG-1 in CRC development and the impact of AEG-1 on the response of radiation treatment. The AEG-1 expression, analysed in different CRC patient cohorts in paper I and III, was increased in the tumour tissue compared with the normal mucosa, and higher in the lymph node and liver metastases. Expression analyses in normal and cancer cell lines confirmed these results. In paper II, sequencing of the complete coding sequence of the MTDH gene in 356 patients revealed 50 single nucleotide variants of which 29 were novel. Eight exonic variants were detected, including three frameshift variants which were probably pathogenic, and two missense variants located in functional protein regions. There was no correlation of the MTDH variants or AEG-1 expression with the patient survival. In paper III, we also investigated the impact of AEG-1 on the response to radiation treatment. AEG-1 knockdown decreased the cellular survival upon radiation in several colon cancer cell lines. The AEG-1 expression was furthermore analysed in patients, which were randomised to either surgery alone or preoperative radiotherapy (RT), followed by surgery. The rectal cancer patients with high AEG-1 expression treated with RT had a significantly higher risk of developing distant recurrence and had a worse disease free survival, likely due to the metastasis promoting properties of AEG-1. In paper IV, the impact of AEG-1 knockdown and radiation on migration and invasion was analysed in colon cancer cell lines in vitro  and in a novel zebrafish model in vivo. AEG-1 knockdown decreased migration and invasion, and radiation-enhanced migration and invasion in the cell lines tested.In conclusion, our data suggest that AEG-1 is involved in CRC development, while MTDH gene variants probably not have a high clinical importance in CRC. Furthermore, AEG-1 is a promising radiosensitising target and a valuable prognostic marker in CRC. We further showed that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced cell migration and invasion.
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43.
  • Gustafsson, Britt, et al. (författare)
  • Evidence of space-time clustering of childhood acute lymphoblastic leukaemia in Sweden
  • 1999
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 79:3/4, s. 655-657
  • Tidskriftsartikel (refereegranskat)abstract
    • We have examined 645 recorded cases of childhood acute lymphatic leukaemia (ALL) in Sweden during 1973–89 to identify space–time clustering by using the close-pair method of Knox. The records included date of birth and of diagnosis as well as addresses at birth and at diagnosis. There was a significant excess of case pairs close in date of birth and place of birth in the 5- to 15-year age group.
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44.
  • Gustafsson, Britt, et al. (författare)
  • Space-time clustering of childhood lymphatic leukaemias and non-Hodgkin's lymphomas in Sweden
  • 2000
  • Ingår i: European Journal of Epidemiology. - 0393-2990 .- 1573-7284. ; 16:12, s. 1111-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The discussion concerning clusters of childhood leukaemia has mainly been focused on their relation to the time and place of diagnosis. Recently some studies have indicated clustering not only at diagnosis, but also around time and place of birth. Space-time clustering at time of birth could be of special interest if the aetiological agent is of infectious origin and the induction of leukaemia either occurs pre- or perinatally or an infection at that time favours a poor subsequent immune response to the agent. Methods: To identify possible space-time clustering we have used the close-pair method of Knox. One-thousand-twenty recorded cases (0-14 years) of childhood acute lymphatic leukaemia and 293 cases (0-14 years) of malignant non-Hodgkin's lymphoma from Sweden between 1973-1996 were analysed. The records include date of birth and of diagnosis as well as addresses at birth and at diagnosis. Results: A significant excess of case-pairs (25 observed, 14.9 expected, p = 0.01) was observed close in date and place of birth in the 4-14 year age group with acute lymphatic leukaemia (ALL). However there was no statistically significant clustering found around time of diagnosis. When the cases of leukaemia and the non-Hodgkin's lymphomas were combined no statistically significant clustering was obtained neither at birth nor at diagnosis. Conclusions: This study strengthens the evidence of space-time clustering around the birth date in children whom later developed ALL. This observation is in support of the hypothesis that pre- or perinatal infections can induce a process leading to ALL.
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45.
  • Hatschek, T, et al. (författare)
  • Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial
  • 2012
  • Ingår i: Breast Cancer Research and Treatment. - New York, USA : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 131:3, s. 939-947
  • Tidskriftsartikel (refereegranskat)abstract
    • Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(A (R))) and paclitaxel (Taxol(A (R))) alone (ET) or in combination with capecitabine (Xeloda(A (R)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.
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46.
  • Holmqvist, A, et al. (författare)
  • The location of lymphangiogenesis is an independent prognostic factor in rectal cancers with or without preoperative radiotherapy
  • 2010
  • Ingår i: ANNALS OF ONCOLOGY. - : Elsevier BV. - 0923-7534. ; 21:3, s. 512-517
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lymphangiogenesis and angiogenesis are essential for tumour development and progression. The lymphatic vessel density (LVD) and blood vessel density (BVD) and their relationship to outcome have been studied extensively, however the clinical significance of the location of LVD/BVD in tumour is not known. In the present study, the location and degree of LVD/BVD and their relationship to preoperative radiotherapy (RT), clinicopathological, histopathological and biological factors were studied in rectal cancer patients participating in a Swedish clinical trial of preoperative RT. Patients and methods: The location and degree of LVD/BVD were analysed in primary tumours (n = 138/140) and in their subgroups of non-RT (n = 74) and RT (n = 64/66). Further, the degree of LVD/BVD was examined in the corresponding distant normal mucosa (n = 35/31) and adjacent normal mucosa (n = 72/91). All sections were immunohistochemically examined by using D2-40 and CD34 antibodies. Results: In the whole series of the patients, a higher LVD at the periphery was related to negative p53 expression (P = 0.03) and favourable survival independent of tumour-node-metastasis stage, differentiation and p53 expression (P = 0.03). LVD was increased in p53-negative tumours after RT (P = 0.01). Conclusion: LVD at the periphery of the tumour was an independent prognostic factor in rectal cancer patients.
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47.
  • Holmqvist Knutsen, Annica, 1974-, et al. (författare)
  • PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy : A study in a Swedish rectal cancer trial of preoperative radiotherapy
  • 2012
  • Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 12:65
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients. Material and Methods: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by Western blot. Results: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (p = 0.03). No survival relationship in patients with RT was observed (p = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (p = 0.68)/inner tumour area (p = 0.49). Conclusions: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.  
  •  
48.
  • Jacobsson, Fredric, 1960-, et al. (författare)
  • Caring externalities in health economic evaluation : How are they related to severity of illness?
  • 2005
  • Ingår i: Health Policy. - : Elsevier BV. - 0168-8510 .- 1872-6054. ; 73:2, s. 172-182
  • Tidskriftsartikel (refereegranskat)abstract
    • In health economic evaluations, altruistic preferences in the form of caring externalities, i.e. that people care about others' health, is usually not taken into account. In this study we examined how people value their own and others' health. This pilot study was carried out by letting people answer willingness to pay (WTP) questionnaires where internal WTP (own health) and altruistic WTP (others' health) were isolated and examined. A common method used in health economic evaluations is cost-utility analysis, which is based on the maximisation of QALYs. QALY maximisation may be appropriate if altruistic preferences are non-existent or if they are linear in relation to internal preferences (QALYs gained). We found evidence for the existence of altruistic preferences and that these preferences were relatively higher for severe health states (and lower for mild states of health) compared to internal preferences, i.e. when severity of illness increased, the relative increase in caring was higher concerning others than oneself. The difference was statistically significant (P < 0.001). Our results indicate that more attention and resources should be directed to severe health states, as compared to mild health states, than advocated by internal preferences in order to obtain more efficient resource allocation in the health care sector. © 2004 Elsevier Ireland Ltd. All rights reserved.
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49.
  • Johansson, Yvonne, et al. (författare)
  • Malnutrition in a home-living older population : prevalence, incidence and risk factors. A prospective study
  • 2009
  • Ingår i: JOURNAL OF CLINICAL NURSING. - : Wiley. - 0962-1067 .- 1365-2702. ; 18:9, s. 1354-1364
  • Tidskriftsartikel (refereegranskat)abstract
    • To prospectively investigate and describe the prevalence and incidence of malnutrition among home-living older people, related to demographic and medical factors, self-perceived health and health-related quality of life. Another aim was to find predictors for developing risk of malnutrition. Risk factors for malnutrition have previously been identified as diseases, several medications, low functional status, symptoms of depression and inadequate nutrient intake. Most studies are cross-sectionally performed at hospitals or in nursing care settings. A prospective study with a sample of 579 home-living older people, randomly selected from a local national register. Examinations were performed at baseline and yearly follow-ups two to four times. Questionnaires validated and tested for reliability, to detect risk of malnutrition (Mini Nutritional Assessment), symptoms of depression (Geriatric Depression Scale-20), cognitive function (Mini Mental State Examination), health-related quality of life (Nottingham Health Profile), well-being (Philadelphia Geriatric Center Multilevel Assessment Instrument) self-perceived health, demographic factors, anthropometry and biochemical examinations. Predictors were searched for through multiple logistic regression analysis with the MNA as dependent factor. The prevalence of risk for malnutrition was 14.5%, according to the MNA. Two risk factors for malnutrition were lower handgrip strength and lower self-perceived health. The incidence of risk for malnutrition at follow-ups was between 7.6% and 16.2%. Predictors for developing malnutrition were higher age, lower self-perceived health and more symptoms of depression. Men with symptoms of depression had a higher risk of developing malnutrition. Lower self-perceived health had the highest power to predict risk for malnutrition, with increased number of depression symptoms and higher age as second and third predictors. A regular and combined assessment using the Mini Nutrition Assessment, Geriatric Depression Scale-20 and self-perceived health as a base for identifying people in need, is one way to prevent the development of malnutrition.
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50.
  • Johansson, Yvonne, et al. (författare)
  • Self-perceived health among older men living in their own residence : a four year follow-up study
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • This study characterize older men, who perceived themselves as healthy, with focus on demographical, social, medical and functional factors, and describe changes within the healthy group over time and find predictors of self-perceived health. The study has a prospective design and included 303 men, 75 and 80 years old, living in a municipality in the south of Sweden. Data collection took place 2001-2006 in a total of three – five examinations at an interval of one year. The examinations included questionnaires validated and tested for reliability, assessing the nutritional status, (Mini Nutritional Assessment), symptoms of depression (Geriatric Depression Scale-20), cognitive function (Mini Mental State Examination), health-related quality of life (Nottingham Health Profile), wellbeing (Philadelphia Geriatric Centre Multilevel Assessment Instrument), demographic factors, physical- and biochemical assessments. The men were divided into two groups according to their self-perceived health, 58% (n=175) perceived themselves as healthy and 42% n=128) as less healthy. Good physical health, the ability to walk a distance outdoors, an ability to maintain a social network and having energy were factors important to feeling healthy among men at baseline. Analyses at the follow-ups included men whom still perceived themselves as healthy and men who perceived their health as being impaired. Seventy five percent (n=132) of the healthy group at baseline still perceived themselves as healthy at the first follow-up. Important factors for a self perceived good health when growing older were feeling mentally well and being able to walk up and downstairs. These results indicated that areas representing the individuals own perception and ability are important to feel healthy.
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