| 1. |
|
|
| 2. |
- Moukaddam, M., et al.
(författare)
-
In-beam internal conversion electron spectroscopy with the SPICE detector
- 2018
-
Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 905, s. 180-187
-
Tidskriftsartikel (refereegranskat)abstract
- The SPectrometer for Internal Conversion Electrons (SPICE) has been commissioned for use in conjunction with the TIGRESS γ-ray spectrometer at TRIUMF's ISAC-II facility. SPICE features a permanent rare-earth magnetic lens to collect and direct internal conversion electrons emitted from nuclear reactions to a thick, highly segmented, lithium-drifted silicon detector. This arrangement, combined with TIGRESS, enables in-beam γ-ray and internal conversion electron spectroscopy to be performed with stable and radioactive ion beams. Technical aspects of the device, capabilities, and initial performance are presented.
|
|
| 3. |
|
|
| 4. |
- van Rheenen, W, et al.
(författare)
-
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
-
Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
|
|
| 5. |
- Dunlop, R., et al.
(författare)
-
β decay and β-delayed neutron decay of the N=82 nucleus 13149In82
- 2019
-
Ingår i: Physical Review C: covering nuclear physics. - 2469-9985.
-
Tidskriftsartikel (refereegranskat)abstract
- The half-lives of three β-decaying states of 13149In82 have been measured with the GRIFFIN γ-ray spectrometer at the TRIUMF-ISAC facility to be T1/2(1/2−)=328(15)ms, T1/2(9/2+)=265(8)ms, and T1/2(21/2+)=323(55)ms, respectively. The first observation of γ rays following the βn decay of 131In into 130Sn is reported. The β-delayed neutron emission probability is determined to be P1n=12(7)% for the 21/2+ state and 2.3(3)% from the combined 1/2− and 9/2+ states of 13149In82 observed in this experiment. A significant expansion of the decay scheme of 131In, including 17 new excited states and 35 new γ-ray transitions in 13150Sn81 is also reported. This leads to large changes in the deduced β-branching ratios to some of the low-lying states of 131Sn compared to previous work with implications for the strength of the first-forbidden β transitions in the vicinity of doubly magic 13250Sn82.
|
|
| 6. |
- van Rheenen, Wouter, et al.
(författare)
-
Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
-
Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
|
|
| 7. |
- Bradley, Patrick J., et al.
(författare)
-
Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid gland
- 2024
-
Ingår i: VIRCHOWS ARCHIV. - 0945-6317 .- 1432-2307. ; 485, s. 3-11
-
Forskningsöversikt (refereegranskat)abstract
- Primary squamous cell carcinoma of the parotid gland (pSCCP) has long been recognized as a separate entity and is included in the WHO classifications of salivary gland tumors. However, it is widely accepted among head and neck pathologists that pSCCP is exceptionally rare. Yet, there are many publications describing series of pSCCP and data from SEER and other cancer register databases indicate erroneously an increasing incidence of pSCCP. Importantly, pSCCP and metastatic (secondary) squamous cell carcinoma to the parotid gland (mSCCP) have nearly identical histological features, and the diagnosis of pSCCP should only be made after the exclusion of mSCCP. Moreover, all of the histological diagnostic criteria proposed to be in favor of pSCCP (such as, for example, dysplasia of ductal epithelium) can be encountered in unequivocal mSCCP, thereby representing secondary growth along preexistent ducts. Squamous cell differentiation has also been reported in rare genetically defined primary parotid carcinomas, either as unequivocal histological squamous features (e.g., NUT carcinoma, mucoepidermoid carcinoma), by immunohistochemistry (e.g., in NUT carcinoma, adamantinoma-like Ewing sarcoma, basal-type salivary duct carcinoma, mucoepidermoid carcinoma), or a combination of both. Another major issue in this context is that the International Classification of Diseases (ICD) coding system does not distinguish between primary or metastatic disease, resulting in a large number of patients with mSCCP being misclassified as pSCCP. Immunohistochemistry and new molecular biomarkers have significantly improved the accuracy of the diagnosis of many salivary gland neoplasms, but until recently there were no biomarkers that can accurately distinguish between mSCCP and pSCCP. However, recent genomic profiling studies have unequivocally demonstrated that almost all SCCP analyzed to date have an ultraviolet light (UV)-induced mutational signature typical of mSCCP of skin origin. Thus, mutational signature analysis can be a very useful tool in determining the cutaneous origin of these tumors. Additional molecular studies may shed new light on this old diagnostic and clinical problem. This review presents a critical view of head and neck experts on this topic.
|
|
| 8. |
- Hellquist, H., et al.
(författare)
-
Development of head and neck pathology in Europe
- 2022
-
Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480:5, s. 951-965
-
Tidskriftsartikel (refereegranskat)abstract
- This review gives a brief history of the development of head and neck pathology in Europe from a humble beginning in the 1930s to the explosive activities the last 15 years. During the decades before the introduction of immunohistochemistry in the 1980s, head and neck pathology grew as a subspeciality in many European countries. In the late 1940s, the Institute of Laryngology and Otology with its own pathology laboratory was founded in London, and in 1964 the World Health Organization (WHO) International Reference Centre for the Histological Classification of Salivary Tumours was established at the Bland-Sutton Institute of Pathology, also in London. International collaboration, and very much so in Europe, led to the publication of the first WHO Classification of Salivary Gland Tumours in 1972. In the 1960s, a salivary gland register was organised in Hamburg and in Cologne the microlaryngoscopy was invented enabling microscopic endoscopic examination and rather shortly afterwards a carbon dioxide laser attached to the microscope became established and laryngeal lesions could be treated by laser vaporisation. During the last three decades, the use of immunohistochemistry supplemented with cytogenetic and refined molecular techniques has greatly facilitated the pathological diagnostics of head and neck lesions and has had a huge impact on research. Collaboration between different European centres has drastically increased partly due to establishment of scientific societies such as the Head and Neck Working Group (HNWG) within the European Society of Pathology and the International Head and Neck Scientific Group (IHNSG). A very large number of European pathologists have contributed to the 2nd, 3rd and 4th WHO books, and are involved in the upcoming 5th edition. Accredited educational meetings and courses are nowadays regularly arranged in Europe. Numerous textbooks on head and neck pathology have been written and edited by European pathologists. The increased collaboration has created larger series of tumours for research and new entities, mainly defined by their genetic abnormalities, are continuously emerging from Europe, particularly regarding salivary gland neoplasms and "undifferentiated" sinonasal tumours. These findings have led to a better and more precise classification and open the possibilities for new treatment strategies.
|
|
| 9. |
- Abbey-Lee, Robin N., et al.
(författare)
-
The Influence of Rearing on Behavior, Brain Monoamines, and Gene Expression in Three-Spined Sticklebacks
- 2018
-
Ingår i: Brain, behavior, and evolution. - Basel : S. Karger AG. - 0006-8977 .- 1421-9743. ; 91:4, s. 201-213
-
Tidskriftsartikel (refereegranskat)abstract
- The causes of individual variation in behavior are often not well understood, and potential underlying mechanisms include both intrinsic and extrinsic factors, such as early environmental, physiological, and genetic differences. In an exploratory laboratory study, we raised three-spined sticklebacks (Gasterosteus aculeatus) under 4 different environmental conditions (simulated predator environment, complex environment, variable social environment, and control). We investigated how these manipulations related to behavior, brain physiology, and gene expression later in life, with focus on brain dopamine and serotonin levels, turnover rates, and gene expression. The different rearing environments influenced behavior and gene expression, but did not alter monoamine levels or metabolites. Specifically, compared to control fish, fish exposed to a simulated predator environment tended to be less aggressive, more exploratory, and more neophobic; and fish raised in both complex and variable social environments tended to be less neophobic. Exposure to a simulated predator environment tended to lower expression of dopamine receptor DRD4A, a complex environment increased expression of dopamine receptor DRD1B, while a variable social environment tended to increase serotonin receptor 5-HTR2B and serotonin transporter SLC6A4A expression. Despite both behavior and gene expression varying with early environment, there was no evidence that gene expression mediated the relationship between early environment and behavior. Our results confirm that environmental conditions early in life can affect phenotypic variation. However, the mechanistic pathway of the monoaminergic systems translating early environmental variation into observed behavioral responses was not detected.
|
|
| 10. |
- Rodrigo, J. P., et al.
(författare)
-
Neutrophil to Lymphocyte Ratio in Oropharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
- 2023
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
-
Forskningsöversikt (refereegranskat)abstract
- Simple Summary Neutrophil-to-lymphocyte ratio (NLR) in peripheral blood samples has been associated with prognosis in several cancers, including head and neck cancer, but in oropharyngeal carcinomas its prognostic value, especially in relation to human papillomavirus (HPV) infection, has been little studied. This meta-analysis, including studies on the prognostic value of NLR in oropharyngeal carcinoma, shows that an elevated pretreatment NLR is associated with a worse prognosis in oropharyngeal cancer, regardless of the type of treatment performed, but this prognostic value appears to be specific to HPV-positive oropharyngeal carcinomas. NLR could be used as an affordable prognostic marker in this type of cancer. Neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in various cancers, including head and neck cancer. However, there is limited information on its role in oropharyngeal squamous cell carcinomas (OPSCC) according to HPV status. This prompted the present meta-analysis. Studies were selected when the prognostic value of NLR prior to treatment was evaluated in OPSCC patients, the cutoff value of NLR was available, and the prognostic value of NLR was evaluated by time-to-event survival analysis. A total of 14 out of 492 articles, including 7647 patients, were analyzed. The results showed a worse prognosis for the patients with a high NLR: The combined hazard ratios (HR) for overall survival (OS) in patients with an elevated NLR was 1.56 (95% confidence interval (CI) 1.21-2.02; p = 0.0006), for disease-free survival was 1.52 (95% CI 1.34-1.73; p < 0.00001), and for recurrence-free survival was 1.86 (95% CI 1.50-2.30; p < 0.00001). This worse prognosis of high NLR was exclusive of HPV-positive patients: HR for OS in the HPV-positive subgroup was 4.05 (95% CI 1.90-8.62 (p = 0.0003), and in the HPV-negative subgroup 0.92 (95% CI 0.47-1.80; p = 0.82). The prognosis of NLR was not influenced by treatment: The HR for OS for patients treated with radiotherapy/chemoradiotherapy (RT/CRT) was 1.48 (95% CI 1.09-2.01; p = 0.01), and for patients treated with surgery (+/- RT/CRT) was 1.72 (95% CI 1.08-2.72; p = 0.02). In conclusion, an elevated NLR relates to worse outcomes in patients with HPV-positive OPSCC.
|
|
