| 1. |
- de Boniface, J., et al.
(författare)
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Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial
- 2017
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference. Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1: 1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years. Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.
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| 2. |
- Dreij, Kristian, et al.
(författare)
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Cancer Risk Assessment of Airborne PAHs Based on in Vitro Mixture Potency Factors
- 2017
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:15, s. 8805-8814
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Tidskriftsartikel (refereegranskat)abstract
- Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants associated with adverse human health effects including cancer. However, the risk of exposure to mixtures is difficult to estimate, and risk assessment by whole mixture potency evaluations has been suggested. To facilitate this, reliable in vitro based testing systems are necessary. Here, we investigated if activation of DNA damage signaling in vitro could be an endpoint for developing whole mixture potency factors (MPFs) for airborne PAHs. Activation of DNA damage signaling was assessed by phosphorylation of Chid and H2AX using Western blotting. To validate the in vitro approach, potency factors were determined for seven individual PAHs which were in very good agreement with established potency factors based on cancer data in vivo. Applying the method using Stockholm air PAH samples indicated MPFs with orders of magnitude higher carcinogenic potency than predicted by established in vivo-based potency factors. Applying the MPFs in cancer risk assessment suggested that 45.4 (6% of all) cancer cases per year in Stockholm are due to airborne PAHs. Applying established models resulted in <1 cancer case per year, which is far from expected levels. We conclude that our in vitro based approach for establishing MPFs could be a novel method to assess whole mixture samples of airborne PAHs to improve health risk assessment.
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| 3. |
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| 4. |
- Göhler, Stella, et al.
(författare)
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Functional germline variants in driver genes of breast cancer
- 2017
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Ingår i: Cancer Causes and Control. - Dordrecht : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 28:4, s. 259-271
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours. Methods: After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs). Altogether 40 SNPs located in the core promoter, 5′- and 3′-UTR or which were nonsynonymous SNPs were genotyped in 782 Swedish incident BC cases and 1,559 matched controls. After statistical analyses, further evaluations related to functional prediction and signatures of selection were performed. Results: TBX3 was associated with BC risk (rs2242442: OR = 0.76, 95% CI 0.64–0.92, dominant model) and with less aggressive tumour characteristics. An association with BC survival and aggressive tumour characteristics was detected for the genes ATR (rs2227928: HR = 1.63; 95% CI 1.00–2.64, dominant model), RUNX1 (rs17227210: HR = 3.50, 95% CI 1.42–8.61, recessive model) and TTN (rs2303838: HR = 2.36; 95% CI 1.04–5.39; rs2042996: HR = 2.28; 95% CI 1.19–4.37, recessive model). According to the experimental ENCODE data all these SNPs themselves or SNPs in high linkage disequilibrium with them (r2 ≥ 0.80) were located in regulatory regions. RUNX1 and TTN showed also several signatures of positive selection. Conclusion: The study gave evidence that germline variants in BC driver genes may have impact on BC risk and/or survival. Future studies could discover further germline variants in known or so far unknown driver genes which contribute to cancer development.
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| 5. |
- Rydenfält, Christofer, et al.
(författare)
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Att skapa en bättre arbetsmiljö i hemtjänsten: Hur arbeta med participativt förändringsarbete i praktiken?
- 2017
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Ingår i: ; , s. 50-50
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Konferensbidrag (refereegranskat)abstract
- I dag arbetar cirka 22 procent av de arbetande kvinnorna i Sverige i vård och omsorgssektorn. Vård och omsorg är en kvinnodominerad sektor som karaktäriseras av höga sjuktal, hög personalomsättning och rekryteringsproblem. Sveriges befolkning blir allt äldre samtidigt som vården av svårt sjuka patienter i allt högre grad flyttas ut från sjukhusen till hemmet. Detta utgör stora utmaningar för hemtjänsten och de personer som arbetar där. Allt pekar på att det kommer behövas mer personal inom hemtjänsten på sikt, vilket ställer de arbetsmiljöproblem och rekryteringsproblem som redan finns på sin spets. I ett försök att minska arbetsmiljöproblemen i hemtjänsten så arbetar vi med dessa frågor i Forte-projektet ”Att skapa en bättre arbetsmiljö i hemtjänsten: participativt förändringsarbete i praktiken”. Detta görs dels genom att sammanställa tidigare forskning samt inventera erfarenheter bland praktiker. Dessutom, kommer vi ta fram och utvärdera organisatoriska interventioner avsedda att tackla verkliga arbetsmiljöproblem i samverkan med 4 kommuner och en privat aktör. Upplägget i projektet är metodologiskt intressant av flera skäl: 1) Utöver genomförandet av en vanlig systematisk litteraturstudie, avser vi komplettera denna med en så kallad realist review. Realist review är en speciell metodik som är avsedd för studier av komplexa interventioner och syftar till att ta fram kunskap om de mekanismer som faktiskt får interventionerna att fungera. 2) Vi vet att det finns många lovande initiativ ute i kommunerna där resultaten dessvärre inte sprids och inga ordentliga utvärderingar görs. Därför avser vi identifiera sådana initiativ via olika kanaler, både formella och informella, och utvärdera dessa enligt realist review-metodiken. Vi kommer också att studera några utvalda initiativ närmare. 3) De interventioner som tas fram i projektet kommer att både utformas och implementeras i samverkan med praktiker med fokus på de problem som de deltagande organisationerna själva identifierar. Som forskare bidrar vi med input till denna process, men praktikerna äger frågan. Under hela processen kommer vi att använda den breda kompetens som finns i projektgruppen om t.ex. belastningsergonomi, genus, psykosocial arbetsmiljö, arbetsmiljöteknik och organisationsteori. Inte minst för att säkerställa att det genomförs grundliga och vetenskapligt sunda utvärderingar av de framtagna interventionerna. Förutom ett antal relevanta och grundligt utvärderade interventioner och en översikt över det vetenskapliga kunskapsläget, kommer projektet att resultera i en databas över svenska organisatoriska förändringar med effekt på arbetsmiljön genomförda av praktiker. Det senare inkluderar svar på frågorna ”hur?”, ”varför” och ”i vilka sammanhang?” olika interventioner fungerar. Svar som är avgörande för den som själv avser testa att implementera interventioner som tagits fram i ett annat sammanhang.Projektet är angeläget av många skäl. För det första är hemtjänstens arbetsmiljö underbeforskad, inte minst vad gäller interventionsprojekt. För det andra är hemtjänsten en bransch där väldigt många arbetar. För det tredje är det dokumenterat att branschen har stora arbetsmiljöproblem, främst belastningsskador och stressrelaterad psykisk ohälsa. Således förväntas den kunskap som skapas i projektet ha potential till att skapa en bättre arbetsmiljö och ett större välbefinnande för en stor grupp människor.
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| 6. |
- Sangchoolie, Behrooz, et al.
(författare)
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Light-weight techniques for improving the controllability and efficiency of ISA-level fault injection tools
- 2017
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Ingår i: Proceedings of IEEE Pacific Rim International Symposium on Dependable Computing, PRDC. - : IEEE Computer Society. - 1541-0110. - 9781509056514 - 9781509056521 ; , s. 68-77
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Konferensbidrag (refereegranskat)abstract
- ISA-level fault injection, i.e. the injection of bitflip faults in Instruction Set Architecture (ISA) registers and main memory words, is widely used for studying the impact of transient and intermittent hardware faults. ISA-level fault injection tools can be characterized by different properties such as repeatability, observability, reachability, intrusiveness, efficiency and controllability. This paper presents two preinjection analysis techniques that improve controllability and efficiency using object code analysis. To improve controllability, we propose a technique for identifying the type of data that is stored in a potential target location. This allows the user to selectively direct fault injections to addresses, data and/or control information. Experimental results show that the data type of 84-100% of the targets locations in 8 programs were successfully identified by this technique. The second technique improves efficiency by fault pruning, i.e., by avoiding injection of faults that is known a priori to be detected by the tested system. This technique leverage the fact that faults in certain bits in the program counter and the stack pointer are always detected by machine exceptions. We show that exclusion of these bits from the fault space could significantly prune the fault space and reduce the time it takes to conduct a fault injection campaign.
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