| 1. |
- Akkoyun, S., et al.
(author)
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AGATA - Advanced GAmma Tracking Array
- 2012
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087 .- 1872-9576. ; 668, s. 26-58
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Journal article (peer-reviewed)abstract
- The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation γ-ray spectrometer. AGATA is based on the technique of γ-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a γ ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of γ-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector- response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer. © 2011 Elsevier B.V. All rights reserved.
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| 2. |
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| 3. |
- Pelletier, F., et al.
(author)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Journal article (peer-reviewed)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
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| 4. |
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| 5. |
- Matejcic, M., et al.
(author)
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Biomarkers of folate and vitamin B12 and breast cancer risk : report from the EPIC cohort
- 2017
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:6, s. 1246-1259
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Journal article (peer-reviewed)abstract
- Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1=1.26; 95% CI 1.00-1.58; P-trend=0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1=1.29; 95% CI 1.02-162; P-trend=0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
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| 6. |
- Munce, S. E. P., et al.
(author)
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Development of the Preferred Components for Co-Design in Research Guideline and Checklist : Protocol for a Scoping Review and a Modified Delphi Process
- 2023
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In: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 12:1
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Research review (peer-reviewed)abstract
- Background: There is increasing evidence that co-design can lead to more engaging, acceptable, relevant, feasible, and even effective interventions. However, no guidance is provided on the specific designs and associated methods or methodologies involved in the process. We propose the development of the Preferred Components for Co-design in Research (PRECISE) guideline to enhance the consistency, transparency, and quality of reporting co-design studies used to develop complex health interventions.Objective: The aim is to develop the first iteration of the PRECISE guideline. The purpose of the PRECISE guideline is to improve the consistency, transparency, and quality of reporting on studies that use co-design to develop complex health interventions. Methods: The aim will be achieved by addressing the following objectives: to review and synthesize the literature on the models, theories, and frameworks used in the co-design of complex health interventions to identify their common elements (components, values or principles, associated methods and methodologies, and outcomes); and by using the results of the scoping review, prioritize the co-design components, values or principles, associated methods and methodologies, and outcomes to be included in the PRECISE guideline.Results: The project has been funded by the Canadian Institutes of Health Research.Conclusions: The collective results of this project will lead to a ready-to-implement PRECISE guideline that outlines a minimum set of items to include when reporting the co-design of complex health interventions. The PRECISE guideline will improve the consistency, transparency, and quality of reports of studies. Additionally, it will include guidance on how to enact or enable the values or principles of co-design for meaningful and collaborative solutions (interventions). PRECISE might also be used by peer reviewers and editors to improve the review of manuscripts involving co-design. Ultimately, the PRECISE guideline will facilitate more efficient use of new results about complex health intervention development and bring better returns on research investments. International Registered Report Identifier (IRRID): PRR1-10.2196/50463
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| 7. |
- Taïeb, David, et al.
(author)
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Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants : an international expert Consensus statement
- 2024
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In: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 20:3, s. 168-184
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Research review (peer-reviewed)abstract
- Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.
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| 8. |
- Cramer, Bradley D., et al.
(author)
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U-Pb (zircon) age constraints on the timing and duration of Wen lock (Silurian) paleocommunity collapse and recovery during the "Big Crisis"
- 2012
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In: Geological Society of America Bulletin. - 0016-7606. ; 124:11-12, s. 1841-1857
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Journal article (peer-reviewed)abstract
- High-precision isotope-dilution U-Pb (zircon) dating was conducted on three volcanic ash fall (bentonite) samples from the Swedish island of Gotland, and on a fourth bentonite from the West Midlands, England. Zircons from the Ireviken, Grotlingbo, Djupvik (Gotland), and Wren's Nest Hill-15 (West Midlands) bentonites yielded weighted mean Pb-206/U-238 ages of 431.83 +/- 0.23/0.67 Ma, 428.45 +/- 035/0.73 Ma, 428.06 +/- 0.2110.66 Ma, and 427.86 +/- 032/0.71 Ma, respectively (analytical/total uncertainties). These biostratigraphically well-controlled age dates effectively bracket the Wenlock Epoch of the Silurian Period and provide control for the duration of one of the major Paleozoic biotic events and associated perturbations to the global carbon cycle (the "Big Crisis" or lundgreni event- graptolites; the NIulde Event-conodonts; the Mulde excursion-carbon isotopes). These new data suggest an older and shorter duration for the recalibration of the Wenlock Series and demonstrate that the cascade of biological and chemical events that took place during the Big Crisis happened on time scales of tens to hundreds of thousands of years.
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| 9. |
- Naudin, Sabine, et al.
(author)
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Healthy lifestyle and the risk of pancreatic cancer in the EPIC study
- 2020
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 35:10, s. 975-986
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Journal article (peer-reviewed)abstract
- Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
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| 10. |
- Nesti, Cedric, et al.
(author)
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Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size : a retrospective, Europe-wide, pooled cohort study
- 2023
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In: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:2, s. 187-194
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Journal article (peer-reviewed)abstract
- BackgroundAwareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.MethodsIn this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.Findings282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).InterpretationThis study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.
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| 11. |
- Carpten, JD, et al.
(author)
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HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome
- 2002
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 32:4, s. 676-680
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Journal article (peer-reviewed)abstract
- We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.
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| 12. |
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| 13. |
- Lemoine, Melissa, et al.
(author)
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Low but contrasting neutral genetic differentiation shaped by winter temperature in European great tits
- 2016
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In: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 118:3, s. 668-685
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Journal article (peer-reviewed)abstract
- Gene flow is usually thought to reduce genetic divergence and impede local adaptation by homogenising gene pools between populations. However, evidence for local adaptation and phenotypic differentiation in highly mobile species, experiencing high levels of gene flow, is emerging. Assessing population genetic structure at different spatial scales is thus a crucial step towards understanding mechanisms underlying intraspecific differentiation and diversification. Here, we studied the population genetic structure of a highly mobile species - the great tit Parus major - at different spatial scales. We analysed 884 individuals from 30 sites across Europe including 10 close-by sites (< 50 km), using 22 microsatellite markers. Overall we found a low but significant genetic differentiation among sites (F-ST = 0.008). Genetic differentiation was higher, and genetic diversity lower, in south-western Europe. These regional differences were statistically best explained by winter temperature. Overall, our results suggest that great tits form a single patchy metapopulation across Europe, in which genetic differentiation is independent of geographical distance and gene flow may be regulated by environmental factors via movements related to winter severity. This might have important implications for the evolutionary trajectories of sub-populations, especially in the context of climate change, and calls for future investigations of local differences in costs and benefits of philopatry at large scales.
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| 14. |
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| 15. |
- Perrier, Vincent, et al.
(author)
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A pelagic myodocopid ostracod from the Silurian of Arctic Russia
- 2015
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In: Journal of Micropalaeontology. - : Copernicus GmbH. - 0262-821X .- 2041-4978. ; 34, s. 51-57
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Journal article (peer-reviewed)abstract
- The Silurian myodocope ostracod Richteria migrans is reported from Arctic Russia, from Kotel'ny Island (New Siberian Islands) and the Taimyr Peninsula in strata of Ludfordian (late Ludlow, Late Silurian) age. These occurrences extend the biogeographical range of R. migrans from tropical to mid latitudes of the Early Palaeozoic Rheic Ocean in the palaeo-Southern Hemisphere, into subtropical regions of the palaeo-Northern Hemisphere on, or adjacent to, the Siberia Palaeocontinent. The new records reinforce the idea that R. migrans had wide dispersal capacity and probably possessed a pelagic lifestyle. It also endorses the use of R. migrans as a biostratigraphical marker fossil for the Ludfordian Stage, Ludlow Series, Upper Silurian.
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| 16. |
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| 17. |
- Suh, Hyun Gyu, et al.
(author)
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Cellular dehydration acutely degrades mood mainly in women : A counterbalanced, crossover trial
- 2021
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In: British Journal of Nutrition. - 0007-1145. ; 125:10, s. 1092-1100
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Journal article (peer-reviewed)abstract
- It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (SD 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (SD 3), post 305 (SD 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (SD 3), post 288 (SD 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (SD 0·9) to 16·6 (SD 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (SD 2·0), 14·1 (SD 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.
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| 18. |
- Suh, HyunGyu, et al.
(author)
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Hypertonic Saline Infusion Acutely Degrades Mood in Healthy Volunteers (P23-014-19)
- 2019
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In: Current Development in Nutrition. - 2475-2991. ; 3:Suppl 1
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Journal article (peer-reviewed)abstract
- Objectives: Mild and moderate dehydration adversely affect mood and cognitive function. During dehydration, hypertonic hypovolemia activates both osmo- and baro-receptors but it is not known which physiological pathway is associated with degraded mood state. This study examined the acute effect of osmoreceptor stimulation on mood.Methods: Sixty healthy adults (50% females, 30 ± 1 y; BMI: 26.9 ± 4.0 kg·m-2) were infused intravenously with 3.0% (HYPER) or 0.9% (ISO) NaCl for 2 h (0.1 ml·kg-1·min-1) using a counterbalanced, crossover design. Blood samples were collected every 30 minutes to measure plasma osmolality (POsm), copeptin (a surrogate marker of vasopressin), and renin-angiotensin-aldosterone system (RAAS) hormones. Mood was assessed with the short version of Profile of Mood State (POMS) questionnaire before and after the infusion.Results: POsm and copeptin increased from 286 ± 3 mmol·kg-1 to 305 ± 4 mmol·kg-1 and from 4.5 ± 3.7 pmol·L-1 to 20.4 ± 12.8 pmol·L-1, respectively in HYPER (P < 0.05), and were unchanged in ISO (P > 0.05). No hormonal differences were observed between trials for RAAS hormones (P > 0.05). During HYPER copeptin, following the 2-h infusion, was greater in females than in males (female: 23.4 ± 13.9 pmol·L-1, male: 17.4 ± 10.9 pmol·L-1; P < 0.05). The POMS total mood disturbance (TMD) score increased from 10.5 ± 0.9 to 16.5 ± 1.6 in HYPER (P < 0.05), but not in ISO (P > 0.05). Among POMS subscales, depression-dejection and fatigue-inertia increased in HYPER compared to ISO (P < 0.05). When TMD responses in the HYPER trial were analyzed with sex as a between-subjects factor, the increase was significant in females (pre: 10.2 ± 1.0, post: 18.6 ± 2.3; P < 0.001) but not in males (pre: 10.8 ± 1.4, post: 14.0 ± 2.0; P > 0.05). The confusion-bewilderment subscales and fatigue-inertia of the POMS were also elevated post HYPER in females (P < 0.05), but not in ISO (P > 0.05) in either sex.Conclusions: Hypertonic saline infusion acutely degrades mood state, and women appear to have a more pronounced response. The underlying mechanisms remain to be determined but may be related to higher copeptin levels in women.The study was registered at ClinicalTrials.gov as NCT02761434.Funding Sources: Danone Research.Supporting Tables Images and/or Graphs:
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| 19. |
- Wood, Sidney A J, et al.
(author)
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A cinefluorographic study of the temporal organization of articulator gestures: Examples from Greenlandic
- 1997
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In: Speech Communication (Special Issue: Speech Production: Models and Data ). - 1872-7182 .- 0167-6393. ; 22:2-3, s. 207-225
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Conference paper (peer-reviewed)abstract
- Movement data on articulator gestures in West Greenlandic are presented in order to elucidate principles of articulator coordination, especially the domain of coarticulation (as distinct from the domain of assimilation), the handling of conflicting demands on articulators, and the relation of vowels to consonants. The present data are consistent with results previously obtained from Swedish and Bulgarian. The Greenlandic informant varied his domain of coarticulation by up to two phonemes either side of the current phoneme; potential gesture conflicts were resolved in accordance with the model of Kozhevnikov and Chistovich, oncoming gestures being delayed when they were antagonistic to ongoing gestures; finally, articulator gestures were organized according to the same principles for both vowels and consonants.
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