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| 2. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 9. |
- Rabaglio, M, et al.
(författare)
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Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.
- 2009
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 20:9, s. 1489-98
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.
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| 10. |
- Ravaioli, A, et al.
(författare)
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p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.
- 2008
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Ingår i: Annals of oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 19:4, s. 660-668
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.
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| 11. |
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| 12. |
- Einbeigi, Z., et al.
(författare)
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A founder mutation of the BRCA1 gene in Western Sweden associated with a high incidence of breast and ovarian cancer
- 2001
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 37:15, s. 1904-1909
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe and characterise a founder mutation of the BRCA1 gene in western Sweden. Of 62 families screened for BRCA mutations, 24 had BRCA1 mutations and two had BRCA2 mutations. Tumours that occurred in family members were histologically reviewed and mutational status was analysed using archival paraffin-embedded tissues. The same BRCA1 mutation, 3171ins5, was found in 16 families who were clustered along the western coast of Sweden. Mutation analysis revealed a maternal linkage in 13 families and a paternal linkage in 3. There was complete agreement between mutation analysis results obtained from blood and archival tissues. The penetrance of breast or ovarian cancer by age 70 years was estimated to be between 59 and 93%. There were no differences in survivals between breast or ovarian cancer patients with the mutation and age-matched controls. Thus, a predominant BRCA1 gene founder mutation associated with a high risk of breast and ovarian cancer has been identified and found to occur in a restricted geographical area, thereby allowing timely and cost-effective mutation screening using blood samples or archival histological material.
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| 14. |
- Wallgren, Arne, 1940, et al.
(författare)
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Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.
- 2003
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 21:7, s. 1205-13
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.
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| 15. |
- Gustafsdottir, Sigrun M., et al.
(författare)
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Detection of individual microbial pathogens by proximity ligation
- 2006
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 52:6, s. 1152-1160
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Nucleic acid amplification allows the detection of single infectious agents. Protein-based assays, although they provide information on ongoing infections, have substantially less detection sensitivity.METHODS: We used proximity ligation reactions to detect proteins on bacteria and virus particles via nucleic acid amplification. Antibodies recognizing viral or bacterial surface proteins were equipped with DNA strands that could be joined by ligation when several antibodies were bound in proximity to surface proteins of individual infectious agents.RESULTS: Detection sensitivities similar to those of nucleic acid-based detection reactions were achieved directly in infected samples for a parvovirus and an intracellular bacterium.CONCLUSIONS: This method enables detection of ligated DNA strands with good sensitivity by real-time PCR and could be of value for early diagnosis of infectious disease and in biodefense.
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| 16. |
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| 17. |
- Pena, FJ, et al.
(författare)
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Identification of sperm morphometric subpopulations in two different portions of the boar ejaculate and its relation to postthaw quality
- 2005
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Ingår i: Journal of Andrology. - : American Society of Andrology. - 0196-3635 .- 1939-4640. ; 26:6, s. 716-723
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Tidskriftsartikel (refereegranskat)abstract
- A statistical approach using sequentially principal component analysis (PCA), clustering, and discriminant analyses was. developed to identify sperm morphometric subpopulations in well-defined portions of the fresh boar ejaculate. Semen was obtained as 2 portions (the first 10 mL of the sperm-rich fraction and the rest of. the ejaculate, respectively) and frozen using a conventional protocol. Before freezing, an aliquot was Used for computer-assisted. sperm morphometry analysis (ASMA). Postthaw quality was evaluated using computer-assisted sperm analysis (CASA), and an annexin-V/PI assay evaluated sperm membranes. The PCA revealed that 3 variables represented more than 78% of the cumulative variance in sperm subpopulations. The clustering and discriminant analyses, based on 5780 individual spermatozoa, revealed the existence of 4 sperm subpopulations. The relative percentage of these subpopulations Varied between boar and ejaculate portions. Linear regression models based on measured morphometric characteristics could account for up to 36% of the percentage of intact sperm membranes postthaw. The ASMA protocol used in our study was useful to detect subtle morphometric differences between spermatozoa, and the combination of this analysis with a multivariate statistical procedure gave hew information on the biological characteristics of boar ejaculates that is not given by conventional sperm analysis.
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| 18. |
- Saravia, F., et al.
(författare)
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Controlled cooling during semen cryopreservation does not induce capacitation of spermatozoa from two portions of the boar ejaculate
- 2007
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Ingår i: International Journal of Andrology. - : Wiley-Blackwell. - 0105-6263 .- 1365-2605. ; 30:6, s. 485-499
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Tidskriftsartikel (refereegranskat)abstract
- Cryopreservation imposes dramatic changes in boar sperm survivability but it is as yet unclear which part of the process affects the spermatozoa the most. The present study monitored, along the entire process of cryopreservation, the stability (PMS) of the architecture of the lipid plasma membrane and its integrity (PMI), as well as the kinetics of the processed spermatozoa using two portions from the boar ejaculate (P1 = the first 10 mL of the sperm-rich fraction, SRF; P2 = the rest of the ejaculate), frozen in a recently developed package, the MiniFlatPack (MFPs, 0.5 x 10(9) sperm/dose). Evaluation was made at four specific stages, viz. S1 = after collection (suspended in Beltsville thawing solution, BTS); S2 = at 15 degrees C (suspended in lactose-egg yolk, LEY); S3 = at 5 degrees C (suspended in LEY plus glycerol); and S4 = post-thaw. Both sperm kinetics (using computer-assisted sperm analysis, CASA) and PMS [i.e. the degree of lipid disorder and of the exteriorization of phosphatidylserine (PS) in the plasma membrane, measured by flow cytometry using Merocyanine-540 (M-540), and Annexin-V (AV) respectively], as well as plasma membrane integrity [PMI, i.e. the degree of membrane damage, measured using Yo-Pro-1 or propidium iodide (PI)] were assessed after incubation in BTS at 38 degrees C. Moreover, spermatozoa were challenged by incubation in modified Brackett-Oliphant medium (mBO+) with 37 mM of bicarbonate at 38 degrees C for 30 min, and their PMS and PMI further explored. Total sperm motility was significantly higher in P1 than in P2 along the entire process (S1-S4; p less than 0.01), decreasing significantly at S4 for both fractions (p less than 0.0001). The proportion of spermatozoa showing linear motility (LinM) was similar between ejaculate portions (P1 and P2), with a significant increase post-thaw (S4; p less than 0.0001). During cooling (S1-S3) but not post-thaw (S4), lateral head displacement (LHD) differed between portions and changed along the stages (p less than 0.01). Sperm velocity differed between portions in S1 (p less than 0.01), but remained similar, independently of the portion, thereafter (S2-S4). Both PMS and the total number of live spermatozoa remained similar between S1 and S3 while incubated in BTS for both ejaculate portions. Sperm mortality increased post-thaw (S4) in both portions but the degree of lipid disorder remained low in the live cells (1.28% for P1; 1.55% for P2). Exposure to mBO+, on the other hand, significantly increased membrane lipid disorder along cooling (S1-S3; p less than 0.0001), increasing the percentages of dead spermatozoa, especially post-thaw (around 70%, both portions). PS-exteriorization (AV) was not evident along the cryopreservation process in control (BTS) samples and exposure to mBO+ only induced minor variations. The data showed that kinetics, PMS and PMI of boar spermatozoa suspended in BTS (S1), LEY (S2) or LEY plus glycerol (S3) were maintained during controlled cooling but were altered by thawing, showing more characteristics of cell injury than of sperm capacitation. The spermatozoa were able to capacitate but the bicarbonate challenge destabilized the plasma membrane during initial cooling and accelerated membrane changes post-thaw. We conclude that capacitation of boar spermatozoa does not occur during controlled cooling.
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| 19. |
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| 20. |
- Al-Essawe, Essraa M, et al.
(författare)
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Seminal plasma influences the fertilizing potential of cryopreserved stallion sperm
- 2018
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Ingår i: Theriogenology. - : Elsevier BV. - 0093-691X .- 1879-3231. ; 115, s. 99-107
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Tidskriftsartikel (refereegranskat)abstract
- Seminal plasma (SP) contains proteins that may influence cryosurvival and prevent capacitation-like changes due to freezing and thawing. The objective of this study was to investigate the effect of adding pooled SP from "good" (GF) or "bad" (BF) freezer stallions on sperm cells' fertilizing ability. "Good freezers" refers to stallions that usually produce ejaculates which can withstand cryopreservation, whilst "bad freezer" stallions produce ejaculates which cannot tolerate the freezing process. A heterologous zona binding assay with in vitro matured bovine oocytes was used to assess the binding ability of equine sperm cells as a possible alternative to artificial insemination trials. The effect of adding SP i) prior to cryopreservation; ii) after thawing of sperm cells selected by single layer centrifugation (SLC); iii) to capacitation medium, was evaluated. Adding SP from GE stallions prior to cryopreservation reduced the mean number of sperm cells bound to the zona pellucida (ZP) compared to control (P = 0.0003), SP-free sperm cells and group received SP from BF stallions (P < 0.0001 for both). After thawing SLC-selected sperm cells treated with 5% SP showed a decrease in binding ability compared with SP-free sperm cells (P < 0.0001). The binding affinity of sperm cells was higher in the group treated with SP from GF than with SP from BF stallions (P < 0.05). Prolonged exposure to SP impaired the ability of stallion sperm cells to undergo capacitation and bind to ZP, regardless of the source of SP (P < 0.0001). The response of equine sperm cells to SP is influenced by the ability of the sperm cells to withstand cryopreservation and is affected by the timing of exposure and the origin of SP. Customization of the protocol for individual stallions is recommended to optimize the effect. (C) 2018 Elsevier Inc. All rights reserved.
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| 21. |
- Aleman, Dionne M., et al.
(författare)
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A fluence map optimization model for restoring traditional fractionation in IMRT treatment planning
- 2014
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Ingår i: Optimization Letters. - : Springer Science and Business Media LLC. - 1862-4472 .- 1862-4480. ; 8:4, s. 1453-1473
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Tidskriftsartikel (refereegranskat)abstract
- One of the core problems in intensity modulated radiation therapy (IMRT) treatment planning is the fluence map optimization (FMO) problem, which determines a fluence map (or profile) for each beam used in the delivery of treatment. Radiation therapy is administered in multiple so-called daily fractions to allow for healthy tissue to recover from damage caused by the treatment. Before the advent of IMRT, the treatment was designed to ensure a constant dose to cells in the target (the areas in the patient where cancerous cells are present or suspected). In the presence of multiple targets with different prescribed doses, this design meant that treatment had to be delivered in a sequence of unequal fractions, one per prescription dose level. For example, in case of two targets treatment would consist of an initial plan aimed at treating both targets to a lower total dose, followed by a so-called boost plan aimed at delivering the additional dose at the target with higher prescribed dose. In contrast, IMRT treatment plans are often delivered with equal treatment plan for each fraction, which means that the dose per fraction cannot be the same for all targets. The important problem of restoring traditional fractionation to IMRT treatments has not yet received much attention in the literature. In this paper we propose a new optimization model that explicitly restores fractionation into the FMO problem, yielding an optimal set of fluence maps for each fraction. We illustrate the capabilities of our approach on clinical head-and-neck cancer cases.
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| 22. |
- Fagerholm, F., et al.
(författare)
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Cognition in Software Engineering: A Taxonomy and Survey of a Half-Century of Research
- 2022
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Ingår i: Acm Computing Surveys. - : Association for Computing Machinery (ACM). - 0360-0300 .- 1557-7341. ; 54:11
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Tidskriftsartikel (refereegranskat)abstract
- Cognition plays a fundamental role in most software engineering activities. This article provides a taxonomy of cognitive concepts and a survey of the literature since the beginning of the Software Engineering discipline. The taxonomy comprises the top-level concepts of perception, attention, memory, cognitive load, reasoning, cognitive biases, knowledge, social cognition, cognitive control, and errors, and procedures to assess them both qualitatively and quantitatively. The taxonomy provides a useful tool to filter existing studies, classify new studies, and support researchers in getting familiar with a (sub) area. In the literature survey, we systematically collected and analysed 311 scientific papers spanning five decades and classified them using the cognitive concepts from the taxonomy. Our analysis shows that the most developed areas of research correspond to the four life-cycle stages, software requirements, design, construction, and maintenance. Most research is quantitative and focuses on knowledge, cognitive load, memory, and reasoning. Overall, the state of the art appears fragmented when viewed from the perspective of cognition. There is a lack of use of cognitive concepts that would represent a coherent picture of the cognitive processes active in specific tasks. Accordingly, we discuss the research gap in each cognitive concept and provide recommendations for future research.
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| 23. |
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| 24. |
- Gunnarsdottir, Frida Björk, et al.
(författare)
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Breast cancer associated CD169(+) macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells
- 2023
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Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- CD169(+) resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169(+) macrophages present in primary breast tumors (CD169(+) TAMs), that correlate with a worse prognosis. We recently showed that these CD169(+) TAMs were associated with tertiary lymphoid structures (TLSs) and T-regs in breast cancer. Here, we show that CD169(+) TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE(2) and inhibitory co-receptor expression pattern. The CD169(+) monocyte-derived macrophages (CD169(+) Mo-M) possessed an immunosuppressive function in vitro inhibiting NK, T and B cell proliferation, but enhanced antibody and IL6 secretion in activated B cells. Our findings indicate that CD169(+) Mo-M in the primary breast tumor microenvironment are linked to both immunosuppression and TLS functions, with implications for future targeted Mo-M therapy.
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| 26. |
- Hultborn, Ragnar, 1946, et al.
(författare)
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Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study
- 1999
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Ingår i: Anticancer Res. - 0250-7005. ; 19:4C, s. 3383-92
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.
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| 30. |
- Karlsson, Adam, et al.
(författare)
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Predicting mortality among septic patients presenting to the emergency department-a cross sectional analysis using machine learning
- 2021
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Ingår i: BMC Emergency Medicine. - : BioMed Central. - 1471-227X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sepsis is a life-threatening condition, causing almost one fifth of all deaths worldwide. The aim of the current study was to identify variables predictive of 7- and 30-day mortality among variables reflective of the presentation of septic patients arriving to the emergency department (ED) using machine learning.Methods: Retrospective cross-sectional design, including all patients arriving to the ED at Sodersjukhuset in Sweden during 2013 and discharged with an International Classification of Diseases (ICD)-10 code corresponding to sepsis. All predictions were made using a Balanced Random Forest Classifier and 91 variables reflecting ED presentation. An exhaustive search was used to remove unnecessary variables in the final model. A 10-fold cross validation was performed and the accuracy was described using the mean value of the following: AUC, sensitivity, specificity, PPV, NPV, positive LR and negative LR.Results: The study population included 445 septic patients, randomised to a training (n = 356, 80%) and a validation set (n = 89, 20%). The six most important variables for predicting 7-day mortality were: "fever", "abnormal verbal response", "low saturation", "arrival by emergency medical services (EMS)", "abnormal behaviour or level of consciousness" and "chills". The model including these variables had an AUC of 0.83 (95% CI: 0.80-0.86). The final model predicting 30-day mortality used similar six variables, however, including "breathing difficulties" instead of "abnormal behaviour or level of consciousness". This model achieved an AUC = 0.80 (CI 95%, 0.78-0.82).Conclusions: The results suggest that six specific variables were predictive of 7- and 30-day mortality with good accuracy which suggests that these symptoms, observations and mode of arrival may be important components to include along with vital signs in a future prediction tool of mortality among septic patients presenting to the ED. In addition, the Random Forests appears to be a suitable machine learning method on which to build future studies.
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| 36. |
- Kumaresan, A., et al.
(författare)
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Quantification of kinetic changes in protein tyrosine phosphorylation and cytosolic Ca2+ concentration in boar spermatozoa during cryopreservation
- 2012
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Ingår i: Reproduction, Fertility and Development. - 1031-3613 .- 1448-5990. ; 24:4, s. 531-542
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Tidskriftsartikel (refereegranskat)abstract
- Protein tyrosine phosphorylation in sperm is associated with capacitation in several mammalian species. Although tyrosine phosphorylated proteins have been demonstrated in cryopreserved sperm, indicating capacitation-like changes during cryopreservation, these changes have not yet been quantified objectively. We monitored tyrosine phosphorylation, intracellular calcium and sperm kinematics throughout the cryopreservation process, and studied the relationships among them in boar spermatozoa. Sperm kinetics changed significantly during cryopreservation: curvilinear velocity, average path velocity and straight line velocity all decreased significantly (P < 0.05). While the percentage of sperm with high intracellular calcium declined (P < 0.05), global phosphorylation increased significantly (P < 0.01). Specifically, cooling to 5 degrees C induced phosphorylation in the spermatozoa. After cooling, a 32-kDa protein not observed in fresh semen appeared and was consistently present throughout the cryopreservation process. While the level of expression of this phosphoprotein decreased after addition of the second extender, frozen-thawed spermatozoa showed an increased expression. The proportion of sperm cells with phosphorylation in the acrosomal area also increased significantly (P < 0.05) during cryopreservation, indicating that phosphorylation might be associated with capacitation-like changes. These results provide the first quantitative evidence of dynamic changes in the subpopulation of boar spermatozoa undergoing tyrosine phosphorylation during cryopreservation.
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| 37. |
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| 38. |
- Larsson, Eric A., et al.
(författare)
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Presentation of the septic patient to the emergency department with respect to age and sex : a retrospective cross-sectional study
- 2022
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Ingår i: BMC Emergency Medicine. - : BioMed Central (BMC). - 1471-227X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: It is challenging to identify sepsis in the emergency department, in part due to the non-specific presentation of septic patients. Current clinical sepsis screening tools rely on vital signs but many patients present with near normal vital signs and are therefore not identified as septic. This suggests that variables, e.g. signs and symptoms, need to be included to improve sepsis detection in the emergency department. Our hypothesis was that the presentation of sepsis differs based age and sex. The potential differences in presentation could be used to apply to future sepsis screening tools. The aim was to analyze the prevalence of keywords reflecting the presentation of septic patients in the emergency department in relation to age and sex.METHOD: Retrospective cross-sectional study. Keywords reflecting sepsis presentation to the emergency department were quantified and compared between age categories and the sex. 479 patients admitted to the emergency department of Södersjukhuset, Stockholm during 2013 and discharged with an ICD-10 code consistent with sepsis were included. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons.RESULT: "Pain" and "risk factors for sepsis" were significantly more common among patients younger than 65 years as compared with those 75 years and older: (n = 87/137; 63.5% vs n = 99/240; 41.3%, P-value < 0.000) and (n = 74/137; 54.0% vs 55/240; 22.9%, P-value < 0.000) respectively. "Risk factors for sepsis" was also significantly more common among patients between 65 and 74 years as compared with those 75 years and older: (n = 43/102; 42.2% vs 55/240; 22.9%, P-value < 0.000). "Pain" and "gastrointestinal symptoms" were significantly more common among women as compared with men: (n = 128/224; 57.1% vs n = 102/255; 40.0%, P-value < 0.000) and (n = 82/244; 36.6% vs n = 55/255; 21.6%, P-value < 0.000) respectively.CONCLUSION: The keywords "pain" and "risk factors for sepsis" were more common among younger patients and "pain" and "gastrointestinal symptoms" were more common among women. However, most keywords had a similar prevalence irrespective of age and sex. The results could potentially be used to augment sepsis screening tools or clinical decision tools.
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| 39. |
- Ljung Aust, Mikael, 1973, et al.
(författare)
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Final measures (Deliverable 5.5)
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The main objective of WP5 has been to run a set of field trials with naïve users (i.e. not experts involved in the development of the measures) for all nudging and coaching measures developed in WP2-4. Then, given the outcome of the field trials, the task has been to analyse which impacts these measures may have on road safety along with the cost of implementing them in vehicle fleets and/or infrastructure. All these activities have taken place in Tasks 5.4 (Data collection) and 5.6 (Data analysis).
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| 40. |
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| 41. |
- Morrell, Jane M., et al.
(författare)
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Selection of Boar Spermatozoa Using Centrifugation on a Glycidoxypropyltrimethoxysilane-Coated Silica Colloid
- 2009
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Ingår i: Journal of reproduction and development. - : Society for Reproduction and Development. - 0916-8818 .- 1348-4400. ; 55:5, s. 547-552
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Tidskriftsartikel (refereegranskat)abstract
- Use of sperm separation methods such as density gradient centrifugation for selecting the best spermatozoa for animal breeding is constrained by the problem of dealing with the large volumes of ejaculate produced by the males of some species, such as boars. The purpose Of this Study was to compare density gradient centrifugation (DGC) with centrifugation on a single layer of colloid (SLC) for the preparation of ejaculated boar spermatozoa using Androcoll (TM)-P. There was no difference between the two techniques in terms of sperm motility or duration of motility after selection, and sperm motility was retained for at least 24 h longer in the centrifuged sperm preparations than in controls (uncentrifuged aliquots). Sperm motility was significantly better (Pless than0.001) in the centrifuged sperm preparations (means +/- sd: SLC 79.6 +/- 8.1% and DGC 74.2 +/- 12.0%) than in the uncentrifuged controls (62.9 +/- 12.7%). The mean yield of motile spermatozoa for SLC was 67.5 +/- 25.6%, and for DGC it was 59.6% +/- 22.3%, (not significant, ns). Sperm survival was significantly increased by colloid centrifugation (control 3.1 +/- 0.3 days, SLC 5.5 +/- 0.79 days, DGC 5.75 +/- 0.62 days; Pless than0.001 for uncentrifuged versus centrifuged, SLC vs. DGC, ns). Moreover, boar spermatozoa could be stored for 24 h before centrifugation without: any detrimental effect on sperm motility or duration of motility. In a further experiment, larger volumes of ejaculate were processed easily on a modified SLC, indicating that this method may be practical for processing large volumes of boar ejaculates.
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| 42. |
- Nicot, A. S., et al.
(författare)
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Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy
- 2007
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Ingår i: Nat Genet. - : Springer Science and Business Media LLC. ; 39:9, s. 1134-1139
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathies are characterized by muscle weakness and abnormal centralization of nuclei in muscle fibers not secondary to regeneration. The severe neonatal X-linked form (myotubular myopathy) is due to mutations in the phosphoinositide phosphatase myotubularin (MTM1), whereas mutations in dynamin 2 (DNM2) have been found in some autosomal dominant cases. By direct sequencing of functional candidate genes, we identified homozygous mutations in amphiphysin 2 (BIN1) in three families with autosomal recessive inheritance. Two missense mutations affecting the BAR (Bin1/amphiphysin/RVS167) domain disrupt its membrane tubulation properties in transfected cells, and a partial truncation of the C-terminal SH3 domain abrogates the interaction with DNM2 and its recruitment to the membrane tubules. Our results suggest that mutations in BIN1 cause centronuclear myopathy by interfering with remodeling of T tubules and/or endocytic membranes, and that the functional interaction between BIN1 and DNM2 is necessary for normal muscle function and positioning of nuclei.
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| 43. |
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| 44. |
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| 45. |
- Pena, F.J., et al.
(författare)
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Detection of early changes in sperm membrane integrity pre-freezing can estimate post-thaw quality of boar spermatozoa
- 2007
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Ingår i: Animal Reproduction Science. - : Elsevier Masson. - 0378-4320 .- 1873-2232. ; 97:1-2, s. 74-83
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Tidskriftsartikel (refereegranskat)abstract
- A recently developed triple staining (SNARF-1/YO-PRO-1/ethidium homodimer) was used to assess early changes in boar sperm membrane integrity (MI) with the results of cryopreservation procedures and to seek for correlations among MI-spermatozoa in pre-freeze semen and its freezeability. Ejaculates from five boars were evaluated in the fresh and frozen-thawed (FT) state, and its freezeability defined as % of membrane intactness, MI% (MI% = % of FT-spermatozoa with intact membranes x 100 divided by the % of prefreeze spermatozoa with intact membranes) estimated. Significant differences were found among boars for freezeability (MI%) and motility post-thaw (%). Interestingly, significant correlations were found between the percentage of YO-PRO-1-positive spermatozoa and freezeability (R = 0.440, p less than 0.01), indicating this new triple staining can be used to safely disclose among ejaculates prior to freezing. (c) 2006 Elsevier B.V. All rights reserved.
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| 46. |
- Rodriguez-Martinez, Heriberto, et al.
(författare)
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Boar spermatozoa in the oviduct
- 2005
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Ingår i: Theriogenology. - : Elsevier. - 0093-691X .- 1879-3231. ; 63:2, s. 514-535
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Tidskriftsartikel (refereegranskat)abstract
- In the pig, a functional tubal sperm reservoir (SR) is established before ovulation to ensure availability of suitable numbers of viable spermatozoa for fertilization. The boars large ejaculate is split: most spermatozoa are delivered in a sperm-rich fraction (SRF) followed by a post-SRF fraction containing increasing amounts of the spermadhesin PSP-I/PSP-II-rich seminal vesicle secretion. This heterodimer acts as leukocyte chemoattractant both in vitro and in vivo, contributing to the phagocytosis of those spermatozoa not reaching the SR. Sequential ejaculate deposition of marked spermatozoa and SR screening showed that most spermatozoa in the SR arose from the fortuitous PSP-poor, first portion of the SRF fraction, escaping phagocytosis and replenishing the SR within 23 h. The SR-sperm numbers diminish gradually in relation to ovulation, spermatozoa. being continuously redistributed toward the upper isthmus. In vitro, only uncapacitated spermatozoa bind to epithelial explants, suggesting that the SR influences sperm capacitation. In vivo, most viable spermatozoa - usually harbored in the deep furrows in the pre- or peri-ovulatory SR during spontaneous standing estrus - are uncapacitated, but capacitation significantly increases after ovulation. Pre-/peri-ovulatory SR spermatozoa promptly capacitate in vitro when exposed to the effector bicarbonate, an influence that can be reversed by co-incubation with SR fluid or its component hyaluronan. Fluid collected from the ampullar segment (rich in bicarbonate) induces capacitation in vitro. In conclusion, the lack of massive sperm capacitation in the SR and the diverse individual response to capacitation shown by tubal spermatozoa would relate both to the insurance of full sperm viability before ovulation and the presence of spermatozoa at different stages of capacitation in the upper oviduct, thus maximizing the chances of normal fertilization. (C) 2004 Elsevier Inc. All rights reserved.
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| 47. |
- Rodriguez-Martinez, Heriberto, et al.
(författare)
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Influence of seminal plasma on the kinematics of boar spermatozoa during freezing
- 2008
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Ingår i: Theriogenology. - : Elsevier. - 0093-691X .- 1879-3231. ; 70:8, s. 1242-1250
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Tidskriftsartikel (refereegranskat)abstract
- Sperm motolity is, for its relation to cell viability and fertility, a central component of the spermiogram, where consideration of motion patterns allows discrimination of sub-populations among boar spermatozoa. Extension and cryo-preservation imposes changes in these patterns in connection to handling, additives, temperature changes and the removal of boar seminal plasma (BSP) which apparently makes spermatozao susceptible to xodative stress, thus affecting survival and motility post-thaw. Detailed kinematic analyses during sperm cooling are sparse, particularly when considering the instrumentation and settings used for analyses, the effect of extenders, and of the BSP the processed spermatozoa are exposed to. Spermatozoa present in the first collectable 10 mL of the sperm-rich fraction of the ejaculate (portion 1. P1-BSP), have shown an increased ability to sustain motility during and after cryo-preservation than spermatozoa immersed in the rest of the ejaculate (portion 2, P2). When P2-spermatozoa were cleansed from their BSP and exposed for 60 min to pooled P1-BSP, their motility post-thaw increased to similar levels as P1-spermatozoa. This BSP-influence is sire-dependent, presumably related to the protein concentration in the different ejaculate poriton,s andapparently unrealted to changes in membrane integrity or membrane stability through conventiona, controlled cooling. (C) 2008 Elsevier Inc. All rights reserved.
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| 48. |
- Rodriguez-Martinez, Heriberto, et al.
(författare)
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Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow
- 2010
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 84:1, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- Seminal plasma (SP) is a complex fluid which exerts biological actions in the female reproductive tract. In pigs, SP elicits endometrial inflammation and consequent immune changes after mating. This study tested whether heparin-binding spermadhesins (HBPs) and the heterodimer of porcine sperm adhesions I and II (PSP-I/PSP-II) in SP recruit different lymphocyte subsets (CD2(+), CD4(+) and CD8(+) T cells) or polymorphonuclear leukocytes (PMNs) to the superficial endometrium or luminal epithelium and lumen, respectively, of oestrous sows. In Experiment 1, endometrial biopsies were taken between 2 and 120 min after infusion of uterine horns with HBPs, PSP-I/PSP-II or saline and evaluated by immunohistochemistry or histology. In Experiment 2, the uterus of oestrous sows was infused with PSP-I/PSP-II or saline to assess PMN numbers in the uterine lumen 3 h later. PSP-I/PSP-II elicited CD2(+) T cell recruitment from 10 min, and CD8(+) T cells from 60 min after infusion, while HBPs increased CD4(+) T cell recruitment by 120 min. PSP-I/PSP-II but not HBPs induced PMN migration to the surface epithelium by 10 min. PMN numbers were elevated 5-fold by 30 min and 7-fold from 60 min. with PMNs detectable in the lumen from 30 min after infusion. Six-fold more PMNs were collected from the uterine lumen of PSP-I/PSP-II-infused sows compared to controls at 3 h after infusion. These data show that PSP-I/PSP-II heterodimer in seminal plasma has a predominant role in triggering the recruitment of uterine PMNs and T cells after mating, initiating a cascade of transient and long-lasting immunological events. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 49. |
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| 50. |
- Rudberg, Peter M., et al.
(författare)
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Beyond generic adaptive capacity : exploring the adaptation space of the water supply and wastewater sector of the Stockholm region, Sweden
- 2012
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Ingår i: Climatic Change. - : Springer Science and Business Media LLC. - 0165-0009 .- 1573-1480. ; 114:3/4, s. 707-721
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines the processes by which the generic adaptive capacity of a system is translated into adaptation to climate change, what form it takes, and what factors facilitate or restrain such processes. This is done by an in-depth analysis of climate change adaptation in the Water supply and Wastewater (WW) sector of the Stockholm region. Observed adaptations are categorized in terms of building adaptive capacity and implementing adaptive decisions, and these measures are analyzed using a model of the adaptation process based on organizational learning theories. In particular, the concept of an organization’s actual adaptation space is defined and used as a means to understand the adaptation options that different WW organizations can pursue, as well as why such options might be pursued. The paper finds that most adaptation measures in the WW sector of the Stockholm region are aimed at building the adaptive capacity of the sector. It also finds that the extent to which adaptation measures can be pursued by the WW organizations is determined principally by how able the organization is to justify the additional resources required for adaptation. The analysis shows that there are two main routes to address this: use of climate knowledge to argue that adaptation is needed, and reference to rules and regulations to show that it is required
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