| 1. |
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| 2. |
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| 3. |
- Bettegowda, Chetan, et al.
(författare)
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Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
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Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
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| 4. |
- Charakida, M., et al.
(författare)
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Endothelial dysfunction in childhood infection
- 2005
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Ingår i: Circulation. - 1524-4539. ; 111:13, s. 1660-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.
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| 5. |
- Johnson, Katherine, et al.
(författare)
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Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression : Diagnostic and mechanistic relevance
- 2022
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2-4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5-8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2-4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p.Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD.Lay summary: MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
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| 6. |
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| 7. |
- Budde, M., et al.
(författare)
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Identification of the hydrogen-saturated self-interstitials in silicon and germanium
- 1998
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 57:18, s. 4397-4412
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Tidskriftsartikel (refereegranskat)abstract
- Silicon and germanium single crystals are implanted with protons. The infrared-absorption spectra of the samples contain sharp absorption lines due to the excitation of hydrogen-related local vibrational modes. The lines at 743.1, 748.0, 1986.5, and 1989.4 cm-1 in silicon and at 700.3, 705.5, 1881.8, and 1883.5 cm-1 in germanium originate from the same defect in the two materials. Measurements on samples coimplanted with protons and deuterons show that the defect contains two equivalent hydrogen atoms. Uniaxial stress measurements are carried out and a detailed analysis of the results is presented. It is shown that the defect has monoclinic-II symmetry, and the orientations of the Si-H and Ge-H bonds of the defect are determined. Ab initio local-density-functional theory is used to calculate the structure and local vibrational modes of the self-interstitial binding one and two hydrogen atoms in silicon and germanium together with the structure of the self-interstitial itself. The observed properties of the defect are in excellent agreement with those calculated for the self-interstitial binding two hydrogen atoms.
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| 8. |
- Budde, M., et al.
(författare)
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The hydrogen-saturated self-interstitial in silicon and germanium
- 1997
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Ingår i: Defects in semiconductors. - : Trans Tech Publications Inc.. ; , s. 35-40
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Konferensbidrag (refereegranskat)abstract
- Infrared absorption spectroscopy is used to study H-related point defects in H+-implanted Si (Si:H) and Ge (Ge:H). The absorption lines at 743.1, 748.0, 1986.5 and 1989.4 cm-1 in Si:H and at 700.3, 705.5, 1881.8 and 1883.5 cm-1 in Ge:H are shown to originate from the same defect containing two equivalent H atoms. Uniaxial stress experiments show that the defects have monoclinic-II symmetry, and the orientations of the two Si-H or Ge-H bonds are determined. The structure and the local vibrational modes of the self-interstitial binding two H atoms (IH2) are calculated with LDF cluster theory. The symmetry, bond-orientations and isotopic frequency-shifts calculated for IH2 are in excellent agreement with those observed for the 743.1-, 748.0-, 1986.5- and 1989.4-cm-1 modes in Si:H and for the 700.3-, 705.5-, 1881.8- and 1883.5-cm-1 modes in Ge:H.
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| 9. |
- Dawson, George J., et al.
(författare)
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Prevalence studies of GB virus-C infection using reverse transcriptase-polymerase chain reaction
- 1996
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Ingår i: Journal of Medical Virology. - 1096-9071. ; 50:1, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- Among the three recently described GB viruses (GBV-A, GBV-B, and GBV-C), only GBV-C has been linked to cryptogenic hepatitis in man. Because of the limited utility of currently available research tests to determine antibody response to GBV-C proteins, the prevalence of GBV-C RNA in human sera was studied using reverse transcription-polymerase chain reaction (RT-PCR). The prevalence of GBV-C is higher among volunteer blood donors with elevated serum alanine aminotransferase (ALT) levels (3.9%) than among volunteer blood donors with normal ALT levels (0.8%). Higher rates were also noted among commercial blood donors (12.9%) and intravenous drug users (16.0%). GBV-C was frequently detected in residents of West Africa, where the prevalence was > 10% in most age groups. Approximately 20% of patients diagnosed with either acute or chronic hepatitis C virus (HCV) were found to be positive for GBV-C RNA. In addition, GBV-C RNA sequences were detected in individuals diagnosed with non-A-E hepatitis, with clinical courses ranging from mild disease to fulminant hepatitis. Fourteen of sixteen subjects with or without clinically apparent hepatitis were positive for GBV-C RNA more than 1 year after the initial positive result.
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| 10. |
- Hoffmann, L., et al.
(författare)
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Substitutional carbon in Ge and Si1-xGex
- 1997
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Ingår i: Defects in semiconductors. - : Trans Tech Publications Inc.. ; , s. 97-102
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Konferensbidrag (refereegranskat)abstract
- In the present work, carbon is implanted into monocrystalline Ge and into relaxed epitaxial MBE-grown Si1-xGex. The samples are studied with infrared absorption spectroscopy along with ion-channeling studies on the Ge samples. Finally, ab-initio local density functional cluster theory is applied to calculate the structure and the local vibrational modes of substitutional carbon, Cs, in Ge. After implantation of 12C+ in Ge at room temperature and subsequent annealing at 350°C, a sharp absorption line is observed at 531 cm-1. By isotope substitution, it is concluded that the 531 cm-1 line represents a local vibrational mode of a single carbon atom. From ion-channeling measurements on samples annealed at 450°C, it is found that 31±3 % of the carbon atoms are located at substitutional sites. The population of the substitutional site and the intensity of the 531 cm-1 mode have identical annealing behavior and it is concluded that the 531 cm-1 mode is the three-dimensional T2 stretch mode of Cs in Ge. The calculated frequency and isotope shift for this mode are in good agreement with the observations. In Si0.65Ge0.35, two broad absorption lines are observed at ∼551 and ∼592 cm-1 after implantation of 12C+ and subsequent annealing at 550°C. From measurements on samples implanted with 13C+ and coimplanted with 12C+ and 13C+ we conclude that these lines represent local vibrational modes of defects containing a single carbon atom. In 13C+ implanted Si1-xGex samples that contain 15 to 50 % Ge a number of modes are observed in a frequency range from ∼510 to ∼610 cm-1, i.e., in the range of Cs in Ge and in Si. From the experimental findings it is concluded that substitutional carbon in Si1-xGex binds to both Si and Ge.
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| 11. |
- Joseph, A, et al.
(författare)
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Metabolic features of cancer cells impact immunosurveillance
- 2021
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types.MethodsTumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PARlow) and cisplatin-resistant (PARhigh) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry.ResultsThe infiltration of tumors by CD8 T and DC-LAMP+ cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p<0.001 for both CD8 T and DC-LAMP cells). We observed a positive correlation between PDXK expression and the infiltration by DC-LAMP (R=0.44, p=0.02 in LACC, R=0.14, p=0.057 in NSCLC), and a negative correlation between PAR levels and CD8 T lymphocytes (R=−0.39, p=0.034 in LACC, R=−0.18, p=0.017 in NSCLC). PARP1 is constitutively hyperactivated in cisplatin-resistant LLC cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PARhigh). Tumors formed by such cancer cells injected into immunocompetent mice were scarcely infiltrated by CD8 T (p=0.028) and antigen presenting cells (p=0.086).ConclusionsOncometabolic features can impact local immunosurveillance, providing new functional links between cisplatin resistance and therapeutic failure.
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| 12. |
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| 13. |
- Scott, J. K., et al.
(författare)
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Centralization of services for children born with orofacial clefts in the United kingdom : a cross-sectional survey
- 2014
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Ingår i: Cleft Palate Craniofac J. - 1545-1569 (Electronic) 1055-6656 (Linking) ; 51:5, s. e102-9
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Tidskriftsartikel (refereegranskat)abstract
- Objective : To examine current provision of cleft lip and/or palate services in the U.K. and compliance with recommendations made by the Clinical Standards Advisory Group (CSAG) in 1998. Design : Cross-sectional questionnaire survey. Setting : All 11 services within the U.K. providing care for children born with a cleft lip and palate. Participants : Members from each healthcare specialty in each U.K. cleft team. Interventions : Self-administered postal questionnaires enquired about the provision of cleft services. Data were collected about the overall cleft service, team coordination, hearing, orthodontics, pediatric dentistry, primary cleft surgery, psychology, restorative dentistry, secondary surgery, specialist cleft nursing, and speech and language therapy. Results : Questionnaires were returned from members of 130/150 cleft teams (87%) and these showed that U.K. cleft services have been restructured to 11 centralized services with 17 primary operative sites and 61 peripheral sites. All services provide care through a multidisciplinary (MDT) model, but the composition of each team varies. Primary cleft surgery and orthodontics were the only specialties that were represented in all cleft teams. Specialties may be represented in a team but their attendance at MDT clinics is variable. Only one team met all of the CSAG recommendations. Conclusions : Our survey shows that cleft services have centralized over the last 10 years, and an MDT model of care has been adopted. Further research is needed to show how this has influenced outcomes and to see whether some models of centralized care are associated with better outcomes.
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| 14. |
- Scott, J. K., et al.
(författare)
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Perceptions of team members working in cleft services in the United Kingdom : a pilot study
- 2015
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Ingår i: Cleft Palate Craniofac J. - 1545-1569 (Electronic) 1055-6656 (Linking) ; 52:1, s. e1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cleft care provision in the United Kingdom has been centralized over the past 15 years to improve outcomes for children born with cleft lip and palate. However, to date, there have been no investigations to examine how well these multidisciplinary teams are performing. METHODS: In this pilot study, a cross-sectional questionnaire surveyed members of all health care specialties working to provide cleft care in 11 services across the United Kingdom. Team members were asked to complete the Team Work Assessment (TWA) to investigate perceptions of team working in cleft services. The TWA comprises 55 items measuring seven constructs: team foundation, function, performance and skills, team climate and atmosphere, team leadership, and team identity; individual constructs were also aggregated to provide an overall TWA score. Items were measured using five-point Likert-type scales and were converted into percentage agreement for analysis. RESULTS: Responses were received from members of every cleft team. Ninety-nine of 138 cleft team questionnaires (71.7%) were returned and analyzed. The median (interquartile range) percentage of maximum possible score across teams was 75.5% (70.8, 88.2) for the sum of all items. Team performance and team identity were viewed most positively, with 82.0% (75.0, 88.2) and 88.4% (82.2, 91.4), respectively. Team foundation and leadership were viewed least positively with 79.0% (72.6, 84.6) and 76.6% (70.6, 85.4), respectively. CONCLUSIONS: Cleft team members perceive that their teams work well, but there are variations in response according to construct.
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| 15. |
- Scott, J. K., et al.
(författare)
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Perceptions of team members working in cleft services in the United Kingdom : a pilot study
- 2015
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Ingår i: Cleft Palate Craniofac J. ; 52:1, s. e1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cleft care provision in the United Kingdom has been centralized over the past 15 years to improve outcomes for children born with cleft lip and palate. However, to date, there have been no investigations to examine how well these multidisciplinary teams are performing. METHODS: In this pilot study, a cross-sectional questionnaire surveyed members of all health care specialties working to provide cleft care in 11 services across the United Kingdom. Team members were asked to complete the Team Work Assessment (TWA) to investigate perceptions of team working in cleft services. The TWA comprises 55 items measuring seven constructs: team foundation, function, performance and skills, team climate and atmosphere, team leadership, and team identity; individual constructs were also aggregated to provide an overall TWA score. Items were measured using five-point Likert-type scales and were converted into percentage agreement for analysis. RESULTS: Responses were received from members of every cleft team. Ninety-nine of 138 cleft team questionnaires (71.7%) were returned and analyzed. The median (interquartile range) percentage of maximum possible score across teams was 75.5% (70.8, 88.2) for the sum of all items. Team performance and team identity were viewed most positively, with 82.0% (75.0, 88.2) and 88.4% (82.2, 91.4), respectively. Team foundation and leadership were viewed least positively with 79.0% (72.6, 84.6) and 76.6% (70.6, 85.4), respectively. CONCLUSIONS: Cleft team members perceive that their teams work well, but there are variations in response according to construct.
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| 16. |
- Toreti, A, et al.
(författare)
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Narrowing uncertainties in the effects of elevated CO2 on crops
- 2020
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Ingår i: Nature Food. - : Springer Science and Business Media LLC. - 2662-1355. ; 1, s. 775-782
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Tidskriftsartikel (refereegranskat)abstract
- Plant responses to rising atmospheric carbon dioxide (CO2) concentrations, together with projected variations in temperature and precipitation will determine future agricultural production. Estimates of the impacts of climate change on agriculture provide essential information to design effective adaptation strategies, and develop sustainable food systems. Here, we review the current experimental evidence and crop models on the effects of elevated CO2 concentrations. Recent concerted efforts have narrowed the uncertainties in CO2-induced crop responses so that climate change impact simulations omitting CO2 can now be eliminated. To address remaining knowledge gaps and uncertainties in estimating the effects of elevated CO2 and climate change on crops, future research should expand experiments on more crop species under a wider range of growing conditions, improve the representation of responses to climate extremes in crop models, and simulate additional crop physiological processes related to nutritional quality.
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| 17. |
- Ambati, Aditya, et al.
(författare)
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Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:12
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Tidskriftsartikel (refereegranskat)abstract
- Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 x 10(-9)) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R-2 = 0.15; P < 2.0 x 10(-22) at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.
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| 18. |
- Coomer, B.J., et al.
(författare)
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Vacancy-hydrogen complexes in germanium
- 1998
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Ingår i: E-MRS Meeting. - : European Materials Research Society.
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Konferensbidrag (refereegranskat)abstract
- Local-density-functional pseudopotential theory is used to investigate the structural, electronic and vibrational properties of vacancy-hydrogen complexes in germanium. The results are compared with recent infrared absorption data from proton and deuteron implanted Ge. The acceptor and donor levels of the VH defects are derived semi-empirically from the relaxed structures
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| 19. |
- Coomer, B.J., et al.
(författare)
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Vacancy-hydrogen complexes in germanium
- 1999
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Ingår i: Materials Science & Engineering. - 0921-5107 .- 1873-4944. ; 58:1-2, s. 36-38
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Tidskriftsartikel (refereegranskat)abstract
- Local-density-functional pseudopotential theory is used to investigate the structural, electronic and vibrational properties of vacancy-hydrogen complexes in germanium. The results are compared with recent infrared absorption data from proton and deuteron implanted Ge. The acceptor and donor levels of the VHn defects are derived semi-empirically from the relaxed structures
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| 20. |
- Hoffman, Lindsey M., et al.
(författare)
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Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG) : A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries
- 2018
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:19, s. 1963-1972
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Tidskriftsartikel (refereegranskat)abstract
- PurposeDiffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs).Materials and MethodsData abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia.ResultsAmong 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration (P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002).ConclusionWe report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.
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| 21. |
- Hoffmann, L., et al.
(författare)
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Substitutional carbon in germanium
- 1997
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 55:17, s. 11167-11173
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Tidskriftsartikel (refereegranskat)abstract
- Carbon impurities implanted into single-crystalline germanium are studied with infrared absorption spectroscopy and ion channeling. After implantation of 12C+ at room temperature and subsequent annealing at 350 °C, a sharp infrared absorption line is observed at 531 cm-1. When 12C+ is substituted by 13C+, the line shifts down in frequency to 512 cm-1 and co-implantation of 12C+ and 13C+ does not give rise to additional lines. Therefore, the 531-cm-1 line represents a local vibrational mode of a defect containing a single carbon atom. Channeling measurements are carried out around the 〈100〉, 〈110〉, and 〈111〉 axes in 12C+-implanted samples annealed at 450 °C. The analysis of the data shows that 31±3 % of the carbon atoms are located at substitutional sites, while the remaining carbon atoms appear to be located randomly. The population of the substitutional site and the intensity of the 531-cm-1 mode have identical temperature dependencies. It is concluded that the 531-cm-1 mode is the three-dimensional T2 stretch mode of substitutional carbon. The effective charge of the mode is determined to be (3.4±0.5)e.mAb initio local density functional cluster theory is applied to calculate the structure and the local vibrational modes of substitutional carbon in germanium. The calculated frequencies and isotope shifts for the T2 stretch mode are in good agreement with the observations.
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| 22. |
- Holley, Rebecca J., et al.
(författare)
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Mucopolysaccharidosis Type I, Unique Structure of Accumulated Heparan Sulfate and Increased N-Sulfotransferase Activity in Mice Lacking alpha-L-iduronidase
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:43, s. 37515-37524
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Tidskriftsartikel (refereegranskat)abstract
- Mucopolysaccharide (MPS) diseases are characterized by accumulation of glycosaminoglycans (GAGs) due to deficiencies in lysosomal enzymes responsible for GAG breakdown. Using a murine model of MPSI Hurler (MPSIH), we have quantified the heparan sulfate (HS) accumulation resulting from alpha-L-iduronidase (Idua) deficiency. HS levels were significantly increased in liver and brain tissue from 12-week-old Idua(-/-) mice by 87- and 20-fold, respectively. In addition, HS chains were shown to contain significantly increased N-, 2-O-, and 6-O-sulfation. Disaccharide compositional analyses also uncovered an HS disaccharide uniquely enriched in MPSIH, representing the terminal iduronic acid residue capping the non-reducing end of the HS chain, where no further degradation can occur in the absence of Idua. Critically, we identified that excess HS, some of which is colocalized to the Golgi secretory pathway, acts as a positive regulator of HS-sulfation, increasing the N-sulfotransferase activity of HS-modifying N-deacetylase/N-sulfotransferase enzymes. This mechanism may have severe implications during disease progression but, now identified, could help direct improved therapeutic strategies.
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| 23. |
- Hughes, C, et al.
(författare)
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An evaluation of current services available for people diagnosed with head and neck cancer in the UK (2009-2010).
- 2012
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Ingår i: Clinical Oncology. - 0936-6555 .- 1433-2981. ; 24:10, s. e187-92
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate current care and service provision for people with head and neck cancer in the UK.MATERIALS AND METHODS: Self-report questionnaires for cancer networks, clinical leads of oncology units and leads for multidisciplinary teams (MDTs) were designed. These questionnaires were based on a previous survey. Questionnaires were sent out between 2009 and 2010.RESULTS: Questionnaires were received from all networks (n = 37), most oncology units (48 of 53) and most MDTs (51 of 63). Care for people with head and neck cancer is increasingly being provided by a centralised MDT. The membership of these teams varies; facilities available for team meetings are fit for purpose in most cases. MDTs are meeting frequently (weekly meetings in 96%) and discussing on average 18 cases at each meeting (95% confidence interval 15-21 cases). Most oncologists have access to all common anti-cancer drugs and most have access to all forms of radiotherapy. Intensity-modulated radiotherapy is not yet available in some oncology units (28%). A small number of units have only one oncologist (13%). Despite audit and research being part of the rationale for MDT working, regular discussion of morbidity and mortality is unusual (40%) and use of a database to record decisions is not universal. Only seven centres record decisions into the Data for Head and Neck Oncology database. Reported recruitment to studies is generally low (<2% of cases enrolled in studies in 62%).CONCLUSIONS: Head and neck cancer care is increasingly provided through a centralised MDT. Increased resources and further changes in practice are required to implement current National Health Service cancer policy. Teams need to improve recording of their decision-making, discuss morbidity and mortality and support recruitment to clinical studies.
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| 24. |
- Leary, P, et al.
(författare)
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Dynamic properties of interstitial carbon and carbon-carbon pair defects in silicon
- 1997
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 55:4, s. 2188-2194
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Tidskriftsartikel (refereegranskat)abstract
- Interstitial carbon, Ci, defects in Si exhibit a number of unexplained features. The Ci defect in the neutral charge state gives rise to two almost degenerate vibrational modes at 920 and 931 cm-1 whose 2:1 absorption intensity ratio naturally suggests a trigonal defect in conflict with uniaxial stress measurements. The dicarbon, Cs-Ci, defect is bistable, and the energy difference between its A and B forms is surprisingly small even though the bonding is very different. In the B form appropriate to the neutral charge state, a silicon interstitial is believed to be located near a bond-centered site between two Cs atoms. This must give rise to vibrational modes which involve the motion of both C atoms in apparent conflict with the results of photoluminescence experiments. We use an ab initio local density functional cluster method, AIMPRO, to calculate the structure and vibrational modes of these defects and find that the ratio of the absorption intensities of the local modes of Ci is in reasonable agreement with experiment even though the structure of the defect is not trigonal. We also show that modes in the vicinity of those detected by photoluminescence for the B form of the dicarbon center involve independent movements of the two C atoms. Finally, the trends in the relative energies of the A and B forms in three charge states are investigated.
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| 25. |
- Nobre, Liana, et al.
(författare)
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Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
- 2020
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Ingår i: JCO Precision Oncology. - 2473-4284. ; 3, s. 561-571
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 by American Society of Clinical Oncology PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P, .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.
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| 26. |
- Pérez, Lance C., et al.
(författare)
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Information Assurance Education in Two- and Four-Year Institutions
- 2011
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Ingår i: Proceedings of the 2011 ITiCSE Working Group Reports (ITiCSE-WGR’11). - New York, NY, USA : ACM. ; , s. 39-53
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Konferensbidrag (refereegranskat)abstract
- The 2011 ITiCSE working group on information assurance (IA) education examined undergraduate curricula at the two- and four-year levels, both within and outside the United States (US). A broad set of two-year IA degree programs were examined in order to get a sense of similarities and differences between them. A broad set of four-year IA degree programs were also examined to explore their similarities and differences. A comparison between the two-year and four-year degree programs revealed that the common challenge of articulation between two- and four-year programs exists in IA as well. The challenge of articulation was explored in some depth in order to understand what remedies might be available. Finally, a number of IA programs at international institutions were examined in order to gain insight into differences between US and non-US IA programs.
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| 27. |
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| 28. |
- Wood, Laura D, et al.
(författare)
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The genomic landscapes of human breast and colorectal cancers.
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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