On flow magnitude and field-flow alignment at Earth's core surface

We present a method to estimate the typical magnitude of flow close to Earth's core surface based on observational knowledge of the geomagnetic main field (MF) and its secular variation (SV), together with prior information concerning field-flow alignment gleaned from numerical dynamo models. An expression linking the core surface flow magnitude to spherical harmonic spectra of the MF and SV is derived from the magnetic induction equation. This involves the angle γ between the flow and the horizontal gradient of the radial field. We study γ in a suite of numerical dynamo models and discuss the physical mechanisms that control it. Horizontal flow is observed to approximately follow contours of the radial field close to high-latitude flux bundles, while more efficient induction occurs at lower latitudes where predominantly zonal flows are often perpendicular to contours of the radial field. We show that the amount of field-flow alignment depends primarily on a magnetic modified Rayleigh number Raη=αg0ΔTD/ηΩ, which measures the vigour of convective driving relative to the strength of magnetic dissipation. Synthetic tests of the flow magnitude estimation scheme are encouraging, with results differing from true values by less than 8 per cent. Application to a high-quality geomagnetic field model based on satellite observations (the xCHAOS model in epoch 2004.0) leads to a flow magnitude estimate of 11-14 km yr−1, in accordance with previous estimates. When applied to the historical geomagnetic field model gufm1 for the interval 1840.0-1990.0, the method predicts temporal variations in flow magnitude similar to those found in earlier studies. The calculations rely primarily on knowledge of the MF and SV spectra; by extrapolating these beyond observed scales the influence of small scales on flow magnitude estimates is assessed. Exploring three possible spectral extrapolations we find that the magnitude of the core surface flow, including small scales, is likely less than 50 km yr−

‘Question Moments’: A Rolling Programme of Question Opportunities in Classroom Science

This article has been made available through the Brunel Open Access Publishing Fund.This naturalistic study integrates specific 'question moments' into lesson plans to increase pupils' classroom interactions. A range of teaching tools has explored students' ideas through opportunities to ask and write questions. Their oral and written outcomes provide data on individual and group misunderstandings. Changes to the schedule of lessons were introduced to discuss these questions and solve disparities. Flexible lesson planning over fourteen lessons across a four-week period of highschool chemistry accommodated students' contributions and increased student participation, promoted inquiring and individualised teaching, with each teaching strategy feeding forward into the next

SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis

<p>Abstract</p> <p>Background</p> <p>Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic <it>NF2 </it>mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the <it>SMARCB1 </it>(<it>INI1</it>) tumor suppressor gene were described in familial and sporadic schwannomatosis patients.</p> <p>Methods</p> <p>To delineate the <it>SMARCB1 </it>gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas.</p> <p>Results</p> <p>Nine variants scattered along the sequence of <it>SMARCB1 </it>were identified. Five of them were classified as deleterious. All five patients carrying a <it>SMARCB1 </it>mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age.</p> <p>Conclusions</p> <p>These results suggest that patients with schwannomas have a significant probability of carrying a <it>SMARCB1 </it>mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the <it>SMARCB1 </it>gene.</p

Case-Control Cohort Study of Patients' Perceptions of Disability in Mastocytosis

BACKGROUND: Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis. METHODOLOGY/PRINCIPAL FINDINGS: In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (> or = 20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level. CONCLUSIONS: On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden

Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations

Background: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. Methods: Specimens of tumor tissue (5-µm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. Results: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. Conclusions: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients. [J Natl Cancer Inst 1998;90:1138-45

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

International audienceAdult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat