| 1. |
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| 2. |
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| 3. |
- Figlioli, G, et al.
(author)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Journal article (peer-reviewed)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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| 8. |
- Barnes, DR, et al.
(author)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Journal article (peer-reviewed)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 9. |
- Coignard, J, et al.
(author)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Journal article (peer-reviewed)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 10. |
- Valassi, E., et al.
(author)
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High mortality within 90 days of diagnosis in patients with Cushing's syndrome: results from the ERCUSYN registry
- 2019
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 181:5, s. 461-472
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Journal article (peer-reviewed)abstract
- Objective: Patients with Cushing's syndrome (CS) have increased mortality. The aim of this study was to evaluate the causes and time of death in a large cohort of patients with CS and to establish factors associated with increased mortality. Methods: In this cohort study, we analyzed 1564 patients included in the European Registry on CS (ERCUSYN); 1045 (67%) had pituitary-dependent CS, 385 (25%) adrenal-dependent CS, 89 (5%) had an ectopic source and 45 (3%) other causes. The median (IQR) overall follow-up time in ERCUSYN was 2.7 (1.2-5.5) years. Results: Forty-nine patients had died at the time of the analysis; 23 (47%) with pituitary-dependent CS, 6 (12%) with adrenal-dependent CS, 18 (37%) with ectopic CS and two (4%) with CS due to other causes. Of 42 patients whose cause of death was known, 15 (36%) died due to progression of the underlying disease, 13 (31%) due to infections, 7 (17%) due to cardiovascular or cerebrovascular disease and 2 due to pulmonary embolism. The commonest cause of death in patients with pituitary-dependent CS and adrenal-dependent CS were infectious diseases (n = 8) and progression of the underlying tumor (n = 10) in patients with ectopic CS. Patients who had died were older and more often males, and had more frequently muscle weakness, diabetes mellitus and ectopic CS, compared to survivors. Of 49 deceased patients, 22 (45%) died within 90 days from start of treatment and 5 (10%) before any treatment was given. The commonest cause of deaths in these 27 patients were infections (n = 10; 37%). In a regression analysis, age, ectopic CS and active disease were independently associated with overall death before and within 90 days from the start of treatment. Conclusion: Mortality rate was highest in patients with ectopic CS. Infectious diseases the commonest cause of death soon after diagnosis, emphasizing the need for careful vigilance at that time, especially in patients presenting with concomitant diabetes mellitus.
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| 11. |
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| 12. |
- Ming, D.W., et al.
(author)
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Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale Crater, Mars
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
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Journal article (peer-reviewed)abstract
- H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.
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| 13. |
- Hakkaart, C, et al.
(author)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Journal article (peer-reviewed)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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| 14. |
- Kim, S. W., et al.
(author)
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Evaluations of NOx and highly reactive VOC emission inventories in Texas and their implications for ozone plume simulations during the Texas Air Quality Study 2006
- 2011
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:22, s. 11361-11386
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Journal article (peer-reviewed)abstract
- Satellite and aircraft observations made during the 2006 Texas Air Quality Study (TexAQS) detected strong urban, industrial and power plant plumes in Texas. We simulated these plumes using the Weather Research and Forecasting-Chemistry (WRF-Chem) model with input from the US EPA's 2005 National Emission Inventory (NEI-2005), in order to evaluate emissions of nitrogen oxides (NOx = NO + NO2) and volatile organic compounds (VOCs) in the cities of Houston and Dallas-FortWorth. We compared the model results with satellite retrievals of tropospheric nitrogen dioxide (NO2) columns and airborne in-situ observations of several trace gases including NOx and a number of VOCs. The model and satellite NO2 columns agree well for regions with large power plants and for urban areas that are dominated by mobile sources, such as Dallas. How-ever, in Houston, where significant mobile, industrial, and inport marine vessel sources contribute to NOx emissions, the model NO2 columns are approximately 50 %-70 % higher than the satellite columns. Similar conclusions are drawn from comparisons of the model results with the TexAQS 2006 aircraft observations in Dallas and Houston. For Dallas plumes, the model-simulated NO2 showed good agreement with the aircraft observations. In contrast, the model-simulated NO2 is similar to 60 % higher than the aircraft observations in the Houston plumes. Further analysis indicates that the NEI-2005 NOx emissions over the Houston Ship Channel area are overestimated while the urban Houston NOx emissions are reasonably represented. The comparisons of model and aircraft observations confirm that highly reactive VOC emissions originating from industrial sources in Houston are underestimated in NEI-2005. The update of VOC emissions based on Solar Occultation Flux measurements during the field campaign leads to improved model simulations of ethylene, propylene, and formaldehyde. Reducing NOx emissions in the Houston Ship Channel and increasing highly reactive VOC emissions from the point sources in Houston improve the model's capability of simulating ozone (O-3) plumes observed by the NOAA WP-3D aircraft, although the deficiencies in the model O-3 simulations indicate that many challenges remain for a full understanding of the O-3 formation mechanisms in Houston.
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| 15. |
- Leshin, L.A., et al.
(author)
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Volatile, Isotope, and Organic Analysis of Martian Fines with the Mars Curiosity Rover
- 2013
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 341:6153
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Journal article (peer-reviewed)abstract
- Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity’s Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.
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| 16. |
- Trainer, P J, et al.
(author)
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Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
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In: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
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Journal article (peer-reviewed)abstract
- Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
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| 17. |
- van der Lely, A J, et al.
(author)
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Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
- 2001
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In: Lancet (London, England). - 0140-6736. ; 358:9295, s. 1754-9
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Journal article (peer-reviewed)abstract
- Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days.Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis.Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353).Pegvisomant is an effective medical treatment for acromegaly.
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| 18. |
- Valassi, E., et al.
(author)
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Worse Health-Related Quality of Life at long-term follow-up in patients with Cushing's disease than patients with cortisol producing adenoma. Data from the ERCUSYN
- 2018
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In: Clinical Endocrinology. - : Wiley. - 0300-0664. ; 88:6, s. 787-798
-
Journal article (peer-reviewed)abstract
- ObjectiveHypercortisolism in Cushing's syndrome (CS) is associated with impaired health-related quality of life (HRQoL), which may persist despite remission. We used the data entered into the European Registry on Cushing's syndrome (ERCUSYN) to evaluate if patients with CS of pituitary origin (PIT-CS) have worse HRQoL, both before and after treatment than patients with adrenal causes (ADR-CS). MethodsData from 595 patients (492 women; 83%) who completed the CushingQoL and/or EQ-5D questionnaires at baseline and/or following treatment were analysed. ResultsAt baseline, HRQoL did not differ between PIT-CS (n=293) and ADR-CS (n=120) on both EuroQoL and CushingQoL. Total CushingQoL score in PIT-CS and ADR-CS was 4118 and 44 +/- 20, respectively (P=.7). At long-time follow-up (>1year after treatment) total CushingQoL score was however lower in PIT-CS than ADR-CS (56 +/- 20 vs 62 +/- 23; P=.045). In a regression analysis, after adjustment for baseline age, gender, remission status, duration of active CS, glucocorticoid dependency and follow-up time, no association was observed between aetiology and HRQoL. Remission was associated with better total CushingQoL score (P<.001), and older age at diagnosis with worse total score (P=.01). Depression at diagnosis was associated with worse total CushingQoL score at the last follow-up (P<.001). ConclusionPIT-CS patients had poorer HRQoL than ADR-CS at long-term follow-up, despite similar baseline scoring. After adjusting for remission status, no interaetiology differences in HRQoL scoring were found. Age and presence of depression at diagnosis of CS may be potential predictors of worse HRQoL regardless of CS aetiology.
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| 19. |
- Casanueva, Felipe F., et al.
(author)
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Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement
- 2017
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In: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20, s. 489-498
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Research review (peer-reviewed)abstract
- © 2017, The Author(s). Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
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| 20. |
- Johannsson, Gudmundur, 1960, et al.
(author)
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Growth Hormone Research Society perspective on biomarkers of GH action in children and adults
- 2018
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In: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:3
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Journal article (peer-reviewed)abstract
- Objective: The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants: GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence: Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process: Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions: The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
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| 21. |
- G. Trainer, Melissa, et al.
(author)
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Seasonal Variations in Atmospheric Composition as Measured in Gale Crater, Mars
- 2019
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In: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 124:11, s. 3000-3024
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Journal article (peer-reviewed)abstract
- The Sample Analysis at Mars (SAM) instrument onboard the Mars Science Laboratory Curiosity rover measures the chemical composition of major atmospheric species (CO2, N2, 40Ar, O2, and CO) through a dedicated atmospheric inlet. We report here measurements of volume mixing ratios in Gale Crater using the SAM quadrupole mass spectrometer, obtained over a period of nearly 5 years (3 Mars years) from landing. The observation period spans the northern summer of MY 31 and solar longitude (LS) of 175° through spring of MY 34, LS = 12°. This work expands upon prior reports of the mixing ratios measured by SAM QMS in the first 105 sols of the mission. The SAM QMS atmospheric measurements were taken periodically, with a cumulative coverage of four or five experiments per season on Mars. Major observations include the seasonal cycle of CO2, N2, and Ar, which lags approximately 20–40° of LS behind the pressure cycle driven by CO2 condensation and sublimation from the winter poles. This seasonal cycle indicates that transport occurs on faster timescales than mixing. The mixing ratio of O2 shows significant seasonal and interannual variability, suggesting an unknown atmospheric or surface process at work. The O2 measurements are compared to several parameters, including dust optical depth and trace CH4 measurements by Curiosity. We derive annual mean volume mixing ratios for the atmosphere in Gale Crater: CO2 = 0.951 (±0.003), N2 = 0.0259 (±0.0006), 40Ar = 0.0194 (±0.0004), O2 = 1.61 (±0.09) x 10‐3, and CO = 5.8 (±0.8) x 10‐4.
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| 22. |
- Ho, Ken, et al.
(author)
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Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?
- 2021
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In: Journal of the Endocrine Society. - : The Endocrine Society. - 2472-1972. ; 5:3
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Research review (peer-reviewed)abstract
- The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
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| 23. |
- Navarro‐González, Rafael, et al.
(author)
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Abiotic Input of Fixed Nitrogen by Bolide Impacts to Gale Crater During the Hesperian : Insights From the Mars Science Laboratory
- 2019
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In: Journal of Geophysical Research - Planets. - : John Wiley & Sons. - 2169-9097 .- 2169-9100. ; 124:1, s. 94-113
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Journal article (peer-reviewed)abstract
- Molecular hydrogen (H2) from volcanic emissions is suggested to warm the Martian surface when carbon dioxide (CO2) levels dropped from the Noachian (4100 to 3700 Myr) to the Hesperian (3700 to 3000 Myr). Its presence is expected to shift the conversion of molecular nitrogen (N2) into different forms of fixed nitrogen (N). Here we present experimental data and theoretical calculations that investigate the efficiency of nitrogen fixation by bolide impacts in CO2‐N2 atmospheres with or without H2. Surprisingly, nitric oxide (NO) was produced more efficiently in 20% H2 in spite of being a reducing agent and not likely to increase the rate of nitrogen oxidation. Nevertheless, its presence led to a faster cooling of the shock wave raising the freeze‐out temperature of NO resulting in an enhanced yield. We estimate that the nitrogen fixation rate by bolide impacts varied from 7 × 10−4 to 2 × 10−3 g N·Myr−1·cm−2 and could imply fluvial concentration to explain the nitrogen (1.4 ± 0.7 g N·Myr−1·cm−2) detected as nitrite (NO2−) and nitrate (NO3−) by Curiosity at Yellowknife Bay. One possible explanation is that the nitrogen detected in the lacustrine sediments at Gale was deposited entirely on the crater's surface and was subsequently dissolved and transported by superficial and ground waters to the lake during favorable wet climatic conditions. The nitrogen content sharply decreases in younger sediments of the Murray formation suggesting a decline of H2 in the atmosphere and the rise of oxidizing conditions causing a shortage in the supply to putative microbial life.
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| 24. |
- Orr, Nick, et al.
(author)
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Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:11, s. 1182-1184
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Journal article (peer-reviewed)abstract
- We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 x 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 x 10(-15); OR = 1.50).
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| 25. |
- Wells, M. L., et al.
(author)
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Harmful algal blooms and climate change: Learning from the past and present to forecast the future
- 2015
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In: Harmful Algae. - : Elsevier BV. - 1568-9883. ; 49, s. 68-93
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Journal article (peer-reviewed)abstract
- Climate change pressures will influence marine planktonic systems globally, and it is conceivable that harmful algal blooms may increase in frequency and severity. These pressures will be manifest as alterations in temperature, stratification, light, ocean acidification, precipitation-induced nutrient inputs, and grazing, but absence of fundamental knowledge of the mechanisms driving harmful algal blooms frustrates most hope of forecasting their future prevalence. Summarized here is the consensus of a recent workshop held to address what currently is known and not known about the environmental conditions that favor initiation and maintenance of harmful algal blooms. There is expectation that harmful algal bloom (HAB) geographical domains should expand in some cases, as will seasonal windows of opportunity for harmful algal blooms at higher latitudes. Nonetheless there is only basic information to speculate upon which regions or habitats HAB species may be the most resilient or susceptible. Moreover, current research strategies are not well suited to inform these fundamental linkages. There is a critical absence of tenable hypotheses for how climate pressures mechanistically affect HAB species, and the lack of uniform experimental protocols limits the quantitative cross-investigation comparisons essential to advancement. A HAB "best practices" manual would help foster more uniform research strategies and protocols, and selection of a small target list of model HAB species or isolates for study would greatly promote the accumulation of knowledge. Despite the need to focus on keystone species, more studies need to address strain variability within species, their responses under multifactorial conditions, and the retrospective analyses of long-term plankton and cyst core data; research topics that are departures from the norm. Examples of some fundamental unknowns include how larger and more frequent extreme weather events may break down natural biogeographic barriers, how stratification may enhance or diminish HAB events, how trace nutrients (metals, vitamins) influence cell toxicity, and how grazing pressures may leverage, or mitigate HAB development. There is an absence of high quality time-series data in most regions currently experiencing HAB outbreaks, and little if any data from regions expected to develop HAB events in the future. A subset of observer sites is recommended to help develop stronger linkages among global, national, and regional climate change and HAB observation programs, providing fundamental datasets for investigating global changes in the prevalence of harmful algal blooms. Forecasting changes in HAB patterns over the next few decades will depend critically upon considering harmful algal blooms within the competitive context of plankton communities, and linking these insights to ecosystem, oceanographic and climate models. From a broader perspective, the nexus of HAB science and the social sciences of harmful algal blooms is inadequate and prevents quantitative assessment of impacts of future HAB changes on human well-being. These and other fundamental changes in HAB research will be necessary if HAB science is to obtain compelling evidence that climate change has caused alterations in HAB distributions, prevalence or character, and to develop the theoretical, experimental, and empirical evidence explaining the mechanisms underpinning these ecological shifts. © 2015 Elsevier B.V.
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