| 1. |
- Ahlin, Cecilia, et al.
(författare)
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Cyclin A is a proliferative marker with good prognostic value in node-negative breast cancer
- 2009
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 18:9, s. 2501-2506
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proliferative markers are not recommended as prognostic factors for clinical use in breast cancer due to lack of standardization in methodology. However, proliferation is driving several gene expression signatures emphasizing the need for a reliable proliferative marker IF or clinical use. Studies suggest that cyclin A is a prognostic marker with satisfying reproducibility. We investigated cyclin A as a prognostic marker in node-negative breast cancer using previously defined cutoff values. Patients and Methods: In a case-control study, we defined 190 women who died from breast cancer as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size <= 50 mm, no lymph node metastases and no adjuvant chemotherapy. Tumor tissues were immunostained for cyclin A using commercially available antibodies. Results: We found a statistically significant association between expression of cyclin A and breast cancer death in a univariate model: odds ratio for cyclin A(ave) 2.7 [95% confidence interval (CI), 1.7-4.3] and cyclin A(max) 3.4 (CI, 2.1-5.5). Corresponding odds ratio for Ki67 were Ki67(ave) 1.9 (CI, 1.2-3.1) and Ki67(max) 1.7 (CI, 1.1-2.7) and for grade 3.1 (CI, 1.8-5.1). Cyclin A was strongly correlated to Ki67 and grade why a model including all was not appropriate. Conclusions: Cyclin A is a prognostic factor for breast cancer death in node-negative patients using standardized methodology regarding scoring and cutoff values. Adding cyclin A as a proliferative marker to established clinicopathologic factors will improve the separation of low and high risk breast cancer.
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| 2. |
- Lymeus, Freddie, et al.
(författare)
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Mindfulness-Based Restoration Skills Training (ReST) in a Natural Setting Compared to Conventional Mindfulness Training : Psychological Functioning After a Five-Week Course
- 2020
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Restoration skills training (ReST) is a mindfulness-based course that draws on restorative nature experience to facilitate the meditation practice and teach widely applicable adaptation skills. Previous studies comparing ReST to conventional mindfulness training (CMT) showed that ReST has important advantages: it supports beginning meditators in connecting with restorative environmental qualities and in meditating with less effort; it restores their attention regulation capabilities; and it helps them complete the course and establish a regular meditation habit. However, mindfulness theory indicates that effortful training may be necessary to achieve generalized improvements in psychological functioning. Therefore, this study tests whether the less effortful and more acceptable ReST approach is attended by any meaningful disadvantage compared to CMT in terms of its effects on central aspects psychological functioning. We analyze data from four rounds of development of the ReST course, in each of which we compared it to a parallel and formally matched CMT course. Randomly assigned participants (total course starters = 152) provided ratings of dispositional mindfulness, cognitive functioning, and chronic stress before and after the 5-week ReST and CMT courses. Round 4 also included a separately recruited passive control condition. ReST and CMT were attended by similar average improvements in the three outcomes, although the effects on chronic stress were inconsistent. Moderate to large improvements in the three outcomes could also be affirmed in contrasts with the passive controls. Using a reliable change index, we saw that over one third of the ReST and CMT participants enjoyed reliably improved psychological functioning. The risk of experiencing deteriorated functioning was no greater with either ReST or CMT than for passive control group participants. None of the contrasts exceeded our stringent criterion for inferiority of ReST compared with CMT. We conclude that ReST is a promising alternative for otherwise healthy people with stress or concentration problems who would be less likely to complete more effortful CMT. By adapting the meditation practices to draw on restorative setting characteristics, ReST can mitigate the demands otherwise incurred in early stages of mindfulness training without compromising the acquisition of widely applicable mindfulness skills.
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| 3. |
- Nilsson, Cecilia, et al.
(författare)
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High proliferation is associated with inferior Outcome in male breast cancer patients
- 2013
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 26:1, s. 87-94
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. Modern Pathology (2013) 26, 87-94; doi:10.1038/modpathol.2012.145; published online 24 August 2012
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| 4. |
- Nilsson, Cecilia, et al.
(författare)
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Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:1, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Background. Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters. Material and methods. In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. Results. Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size andgt;20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. Conclusion. MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.
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| 5. |
- Alerstam, Thomas, et al.
(författare)
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Convergent patterns of long-distance nocturnal migration in noctuid moths and passerine birds.
- 2011
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 278, s. 3074-3080
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Tidskriftsartikel (refereegranskat)abstract
- Vast numbers of insects and passerines achieve long-distance migrations between summer and winter locations by undertaking high-altitude nocturnal flights. Insects such as noctuid moths fly relatively slowly in relation to the surrounding air, with airspeeds approximately one-third of that of passerines. Thus, it has been widely assumed that windborne insect migrants will have comparatively little control over their migration speed and direction compared with migrant birds. We used radar to carry out the first comparative analyses of the flight behaviour and migratory strategies of insects and birds under nearly equivalent natural conditions. Contrary to expectations, noctuid moths attained almost identical ground speeds and travel directions compared with passerines, despite their very different flight powers and sensory capacities. Moths achieved fast travel speeds in seasonally appropriate migration directions by exploiting favourably directed winds and selecting flight altitudes that coincided with the fastest air streams. By contrast, passerines were less selective of wind conditions, relying on self-powered flight in their seasonally preferred direction, often with little or no tailwind assistance. Our results demonstrate that noctuid moths and passerines show contrasting risk-prone and risk-averse migratory strategies in relation to wind. Comparative studies of the flight behaviours of distantly related taxa are critically important for understanding the evolution of animal migration strategies.
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| 6. |
- Bauer, Silke, et al.
(författare)
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The grand challenges of migration ecology that radar aeroecology can help answer
- 2019
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Ingår i: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 42:5, s. 861-875
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Tidskriftsartikel (refereegranskat)abstract
- Many migratory species have experienced substantial declines that resulted from rapid and massive expansions of human structures and activities, habitat alterations and climate change. Migrants are also recognized as an integral component of biodiversity and provide a multitude of services and disservices that are relevant to human agriculture, economy and health. The plethora of recently published studies reflects the need for better fundamental knowledge on migrations and for better management of their ecological and human-relevant effects. Yet, where are we in providing answers to fundamental questions and societal challenges?. Engaging a broad network of researchers worldwide, we used a horizon-scan approach to identify the most important challenges which need to be overcome in order to gain a fuller understanding of migration ecology, and which could be addressed using radar aeroecological and macroecological approaches. The top challenges include both long-standing and novel topics, ranging from fundamental information on migration routes and phenology, orientation and navigation strategies, and the multitude of effects migrants may have on resident communities, to societal challenges, such as protecting or preventing migrant services and disservices, and the conservation of migrants in the face of environmental changes. We outline these challenges, identify the urgency of addressing them and the primary stakeholders – researchers, policy makers and practitioners, or funders of research.
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| 7. |
- Bayani, Jane, et al.
(författare)
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Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- 2021
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Ingår i: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
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| 8. |
- Chapman, Jason W, et al.
(författare)
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Adaptive strategies in nocturnally migrating insects and songbirds: contrasting responses to wind.
- 2016
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Ingår i: Journal of Animal Ecology. - : Wiley. - 1365-2656 .- 0021-8790. ; 85:1, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- 1. Animals that use flight as their mode of transportation must cope with the fact that their migration and orientation performance is strongly affected by the flow of the medium they are moving in, i.e. by the winds. Different strategies can be used to mitigate the negative effects and benefit from the positive effects of a moving flow. The strategies an animal can use will be constrained by the relationship between the speed of the flow and the speed of the animal's own propulsion in relation to the surrounding air. 2. Here we analyse entomological and ornithological radar data from north-western Europe to investigate how two different nocturnal migrant taxa, the noctuid moth Autographa gamma and songbirds, deal with wind by analysing variation in resulting flight directions in relation to the wind-dependent angle between the animal's heading and track direction. 3. Our results, from fixed locations along the migratory journey, reveal different global strategies used by moths and songbirds during their migratory journeys. As expected, nocturnally migrating moths experienced a greater degree of wind drift than nocturnally migrating songbirds, but both groups were more affected by wind in autumn than in spring. 4. The songbirds' strategies involve elements of both drift and compensation, providing some benefits from wind in combination with destination and time control. In contrast, moths expose themselves to a significantly higher degree of drift in order to obtain strong wind assistance, surpassing the songbirds in mean ground speed, at the cost of a comparatively lower spatiotemporal migratory precision. 5. Moths and songbirds show contrasting but adaptive responses to migrating through a moving flow, which are fine-tuned to the respective flight capabilities of each group in relation to the wind currents they travel within. This article is protected by copyright. All rights reserved.
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| 9. |
- Chapman, Jason W., et al.
(författare)
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Detection of flow direction in high-flying insect and songbird migrants
- 2015
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 25:17, s. 751-752
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Tidskriftsartikel (refereegranskat)abstract
- Goal-oriented migrants travelling through the sea or air must cope with the effect of cross-flows during their journeys if they are to reach their destination [1–3] . In order to counteract flow-induced drift from their preferred course, migrants must detect the mean flow direction, and integrate this information with output from their internal compass, to compensate for the deflection. Animals can potentially sense flow direction by two nonexclusive mechanisms: either indirectly, by visually assessing the effect of the current on their movement direction relative to the ground; or directly, via intrinsic properties of the current [4] . Here, we report the first evidence that nocturnal compass-guided insect migrants use a turbulence-mediated mechanism for directly assessing the wind direction hundreds of metres above the ground. By comparison, we find that nocturnally-migrating songbirds do not use turbulence to detect the flow; instead they rely on visual assessment of wind-induced drift to indirectly infer the flow direction.
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| 10. |
- Dahlgren, Jovanna, 1964, et al.
(författare)
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Prenatal cytokine exposure results in obesity and gender-specific programming.
- 2001
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Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 281:2, s. E326-34
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.
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