| 1. |
- Amirian, E. Susan, et al.
(författare)
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Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk : a report from the Glioma International Case-Control Study
- 2016
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 25:2, s. 282-290
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. (C) 2016 AACR.
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| 2. |
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| 3. |
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| 4. |
- Amirian, E. Susan, et al.
(författare)
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History of chickenpox in glioma risk : a report from the glioma international case-control study (GICC)
- 2016
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Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 5:6, s. 1352-1358
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Tidskriftsartikel (refereegranskat)abstract
- Varicella zoster virus (VZV) is a neurotropic alpha-herpesvirus that causes chickenpox and establishes life-long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case-Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta-analyses of the literature and investigations of the potential biological mechanism, are warranted.
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| 5. |
- Amirian, E. Susan, et al.
(författare)
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The Glioma International Case-Control Study : A Report From the Genetic Epidemiology of Glioma International Consortium
- 2016
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 183:2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.
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| 6. |
- Andersson, Ulrika, et al.
(författare)
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Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer
- 2014
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 16:10, s. 1333-1340
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results: We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions: Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes.
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| 7. |
- Bainbridge, Matthew N, et al.
(författare)
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Germline mutations in shelterin complex genes are associated with familial glioma
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:1
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.
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| 8. |
- Bielack, Stefan S, et al.
(författare)
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Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:20, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped prematurely. Long-term follow-up for events and survival continues.
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| 9. |
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| 10. |
- Chan, Ding Cheng Derrick, et al.
(författare)
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Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region
- 2018
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Summary: The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. Purpose: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. Methods: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. Results: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. Conclusions: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.
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| 11. |
- Dahlin, Anna M., 1979-, et al.
(författare)
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A genome-wide association study on medulloblastoma
- 2020
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Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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| 12. |
- Desjardins, Kewin, et al.
(författare)
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Characterization of a back-illuminated CMOS camera for soft x-ray coherent scattering
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A commercial scientific camera has been adapted and characterized at the SOLEIL Synchrotron with the aim to improve the acquisition capabilities on the soft X-ray coherent scattering experimental station at SEXTANTS beamline. This device is equipped by the last generation of back side illuminated scientific CMOS (BSI-sCMOS) of 2048 by 2048 pixels of 11 μm2 able to acquire low noise images with a frame rate up to 48 Hz. The camera's performance measurements have been done and shows a good level of readout noise, a large full-well capacity, a medium dark current and a good homogeneity, respectively, 1.6 e- rms (in High Gain mode), 80 000 e- (in Low Gain mode),<5 e-/pixel/s and ∼ 1%. The quantum efficiency (QE) measurement has been performed at the soft x-ray branch of the METROLOGIE beamline and gives a relatively good agreement with the expected theoretical values. Finally, the demonstration of the camera's efficiency and of the gain in useful time measurement related to the high frame rate have been performed with a series of Airy patterns images compared with an image recorded using the standard BSI-CDD already in operation at the SEXTANTS beamline.
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| 13. |
- Enciso-Mora, Victor, et al.
(författare)
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Deciphering the 8q24.21 association for glioma
- 2013
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:11, s. 2293-2302
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 x 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 x 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 x 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 x 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.
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| 14. |
- Griesmayer, E., et al.
(författare)
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Applications of single-crystal CVD diamond XBPM detectors with nanometre x-ray beams
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Measurements with a Diamond XBPM were carried out at the MAX IV Laboratory, Lund, Sweden, at the NanoMAX beam line. This was the first investigation of a Diamond XBPM detector with nanometre beams. The effect of diffusion, as well as the position resolution at the smallest available beam sizes were studied.
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| 15. |
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| 16. |
- Jalali, Ali, et al.
(författare)
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Targeted sequencing in chromosome 17q linkage region identifies familial glioma candidates in the Gliogene Consortium
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5, s. 8278-
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Tidskriftsartikel (refereegranskat)abstract
- Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.
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| 17. |
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| 18. |
- Kwan, Johnny S H, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels.
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6684-93
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG) is involved in bone homeostasis and tumor cell survival. Circulating OPG levels are also important biomarkers of various clinical traits, such as cancers and atherosclerosis. OPG levels were measured in serum or in plasma. In a meta-analysis of genome-wide association studies in up to 10,336 individuals from European and Asian origin, we discovered that variants >100 Kb upstream of the TNFRSF11B gene encoding OPG and another new locus on chromosome 17q11.2 were significantly associated with OPG variation. We also identified a suggestive locus on chromosome 14q21.2 associated with the trait. Moreover, we estimated that over half of the heritability of OPG levels could be explained by all variants examined in our study. Our findings provide further insight into the genetic regulation of circulating OPG levels.
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| 19. |
- Liu, Yanhong, et al.
(författare)
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Insight in glioma susceptibility through an analysis of 6p22.3, 12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and non-familial glioma
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:9, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P (trend) <1.0 × 10(-8)). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.
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| 20. |
- Marcouille, O., et al.
(författare)
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Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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| 21. |
- Marina, Neyssa M., et al.
(författare)
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Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1) : an open-label, international, randomised controlled trial
- 2016
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Ingår i: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
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Tidskriftsartikel (refereegranskat)abstract
- Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.
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| 22. |
- Melin, Beatrice S., et al.
(författare)
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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| 23. |
- Ng, Tan Ching, et al.
(författare)
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The Application of Industry 4.0 Technological Constituents for Sustainable Manufacturing : A Content-Centric Review
- 2022
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 14:7, s. 1-21
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Forskningsöversikt (refereegranskat)abstract
- Industry 4.0 has been associated with the rise of disruptive intelligence and informationtechnologies. These cutting-edge technologies have the potential to increase productivity whilesimultaneously having a significant impact on social and environmental sustainability. As a result,manufacturers must evaluate the role of these innovative technologies in sustainable development,as these technologies have the potential to address prevalent sustainability issues. A content-centricstudy of the implementation of these Industry 4.0 cutting-edge technologies in sustainable manufacturing is currently absent. A systematic literature study was conducted to explain the potentialcontribution of these novel technologies to the economic, social, and environmental dimensions ofmanufacturing industries. This study describes how these cutting-edge technologies are used insustainable manufacturing. The findings of this study are particularly beneficial to practitioners whoseek to apply one or more digital technologies to sustainable development.
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| 24. |
- Plivelic, Tomás S., et al.
(författare)
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X-ray tracing, design and construction of an optimized optics scheme for CoSAXS, the small angle x-ray scattering beamline at MAX IV laboratory
- 2019
-
Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A novel optical design for a flexible SAXS beamline at a modern synchrotron has been implemented for the CoSAXS beamline at the 3GeV ring at the MAX TV Laboratory. The performance of the beamline has been simulated through combined ray tracing and wave propagation with the code xrt taking into account the low emittance and highly coherent beam of MAX TV and the short inter-optics distances of the beamline. The total photon flux is estimated to be 1012-1013 ph/s with the coherent flux portion up to 10 % at 7.1 keV. The inhomogeneities in the X-ray beam arising from use of real (non-idealised) mirror surfaces are also modelled using the measured slope profiles of the mirrors. Strategies to mitigate these inhomogeneities are discussed. The optical components for CoSAXS have been constructed and beamline commissioning will start in 2019.
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| 25. |
- Rajaraman, Preetha, et al.
(författare)
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Genome-wide association study of glioma and meta-analysis
- 2012
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Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 131:12, s. 1877-1888
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
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| 26. |
- Robertson, Lindsay B, et al.
(författare)
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Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation
- 2010
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 9:3, s. 413-421
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16(INK4A)/p14(ARF) and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://braintumor.epigenetic.org/). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16(INK4A) or p14(ARF). One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma.
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| 27. |
- Sadetzki, Siegal, et al.
(författare)
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Description of selected characteristics of familial glioma patients : Results from the Gliogene Consortium
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49:6, s. 1335-1345
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Tidskriftsartikel (refereegranskat)abstract
- Background: While certain inherited syndromes (e. g. Neurofibromatosis or LiFraumeni) are associated with an increased risk of glioma, most familial gliomas are nonsyndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained from 14 centres in the United States (US), Europe and Israel as part of the Gliogene Consortium. Methods: Families with 2 or more verified gliomas were recruited between January 2007 and February 2011. Distributions of demographic characteristics and clinical variables of gliomas in the families were described based on information derived from personal questionnaires. Findings: The study population comprised 841 glioma patients identified in 376 families (9797 individuals). There were more cases of glioma among males, with a male to female ratio of 1.25. In most families (83%), 2 gliomas were reported, with 3 and 4 gliomas in 13% and 3% of the families, respectively. For families with 2 gliomas, 57% were among 1st-degree relatives, and 31.5% among 2nd-degree relatives. Overall, the mean (+/- standard deviation [SD]) diagnosis age was 49.4 (+/- 18.7) years. In 48% of families with 2 gliomas, at least one was diagnosed at < 40 y, and in 12% both were diagnosed under 40 y of age. Most of these families (76%) had at least one grade IV glioblastoma multiforme (GBM), and in 32% both cases were grade IV gliomas. The most common glioma subtype was GBM (55%), followed by anaplastic astrocytoma (10%) and oligodendroglioma (8%). Individuals with grades I-II were on average 17 y younger than those with grades III-IV. Interpretation: Familial glioma cases are similar to sporadic cases in terms of gender distribution, age, morphology and grade. Most familial gliomas appear to comprise clusters of two cases suggesting low penetrance, and that the risk of developing additional gliomas is probably low. These results should be useful in the counselling and clinical management of individuals with a family history of glioma. (C) 2012 Elsevier Ltd. All rights reserved.
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| 28. |
- Shete, Sanjay, et al.
(författare)
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Genome-wide association study identifies five susceptibility loci for glioma.
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:8, s. 899-904
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Tidskriftsartikel (refereegranskat)abstract
- To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.
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| 29. |
- Shete, Sanjay, et al.
(författare)
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Genome-wide high-density SNP linkage search for glioma susceptibility loci : results from the gliogene consortium
- 2011
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 71:24, s. 7568-7575
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. Cancer Res; 71(24); 7568-75. (C) 2011 AACR.
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| 30. |
- Solmi, Marco, et al.
(författare)
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Physical and mental health impact of COVID-19 on children, adolescents, and their families :
- 2022
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
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| 31. |
- Solmi, Marco, et al.
(författare)
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The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults) : Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic
- 2022
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Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 393-407
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Tidskriftsartikel (refereegranskat)abstract
- Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.
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| 32. |
- Solmi, Marco, et al.
(författare)
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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
- 2023
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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| 33. |
- Sun, Xiangqing, et al.
(författare)
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A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 21:12, s. 2242-2251
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Tidskriftsartikel (refereegranskat)abstract
- Background: We propose a two-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma.Methods: First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N=281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N=74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are re-estimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis.Results: Using the best fitting segregation models in model-based multipoint linkage analysis, we identified two separate peaks on chromosome 17; the first agreed with a region identified by Shete et al. (1) who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum LOD.Conclusions/Impact: Our approach has the advantage of not requiring markers to be in linkage equilibrium unless the minor allele frequency is small (markers which tend to be uninformative for linkage), and of using more of the available information for LOD-based linkage analysis.
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| 34. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 35. |
- Wibom, Carl, et al.
(författare)
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EGFR gene variants are associated with specific somatic aberrations in glioma
- 2012
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Ingår i: PLOS ONE. - : plosone.org. - 1932-6203. ; 14:Suppl. 3, s. 46-46
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Tidskriftsartikel (refereegranskat)abstract
- A number of gene variants have been associated with an increased risk of developing glioma. We hypothesized that the reported risk variants may be associated with tumor genomic instability. To explore potential correlations between germline risk variants and somatic genetic events, we analyzed matched tumor and blood samples from 95 glioma patients by means of SNP genotyping. The generated genotype data was used to calculate genome-wide allele-specific copy number profiles of the tumor samples. We compared the copy number profiles across samples and found two EGFR gene variants (rs17172430 and rs11979158) that were associated with homozygous deletion at the CDKN2A/B locus. One of the EGFR variants (rs17172430) was also associated with loss of heterozygosity at the EGFR locus. Our findings were confirmed in a separate dataset consisting of matched blood and tumor samples from 300 glioblastoma patients, compiled from publically available TCGA data. These results imply there is a functional effect of germline EGFR variants on tumor progression.
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