Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

Reply to comments by Bourgois et al. (2019) on: “Glacial lake evolution and Atlantic-Pacific drainage reversals during deglaciation of the Patagonia Ice Sheet”

No abstract available

Spontaneous infection of a stable mediastinal cystic mass: A case report

Mediastinal cysts have an unpredictable course but can cause complications such as infection or local pressure effects. Persons with mediastinal cysts can be asymptomatic for many years or can develop symptoms as a result of complications of the cyst. There is a lack of consensus on the best approach to managing those patients without symptoms. In this case report, a 56 year old woman with an indolent mediastinal cyst initially managed conservatively suddenly developed symptoms suggestive of an infected mediastinal cyst requiring surgical resection

Policies for new path development: the case of Oxfordshire

This chapter reflects on how evolutionary economic geography (EEG) can be extended to incorporate public policy in its explanations of path development. A weakness of EEG is the poor conceptualisation of the role of the state (central, regional, local) in regional path development. It is therefore argued that a multi-scalar perspective of policy is required and that a large set of policies deserve attention. Oxfordshire in the UK is used to explore the link between public policy and path development

Identification of candidate genome regions controlling disease resistance in Arachis

<p>Abstract</p> <p>Background</p> <p>Worldwide, diseases are important reducers of peanut (<it>Arachis hypogaea</it>) yield. Sources of resistance against many diseases are available in cultivated peanut genotypes, although often not in farmer preferred varieties. Wild species generally harbor greater levels of resistance and even apparent immunity, although the linkage of agronomically un-adapted wild alleles with wild disease resistance genes is inevitable. Marker-assisted selection has the potential to facilitate the combination of both cultivated and wild resistance loci with agronomically adapted alleles. However, in peanut there is an almost complete lack of knowledge of the regions of the <it>Arachis </it>genome that control disease resistance.</p> <p>Results</p> <p>In this work we identified candidate genome regions that control disease resistance. For this we placed candidate disease resistance genes and QTLs against late leaf spot disease on the genetic map of the A-genome of <it>Arachis</it>, which is based on microsatellite markers and legume anchor markers. These marker types are transferable within the genus <it>Arachis </it>and to other legumes respectively, enabling this map to be aligned to other <it>Arachis </it>maps and to maps of other legume crops including those with sequenced genomes. In total, 34 sequence-confirmed candidate disease resistance genes and five QTLs were mapped.</p> <p>Conclusion</p> <p>Candidate genes and QTLs were distributed on all linkage groups except for the smallest, but the distribution was not even. Groupings of candidate genes and QTLs for late leaf spot resistance were apparent on the upper region of linkage group 4 and the lower region of linkage group 2, indicating that these regions are likely to control disease resistance.</p

The Polarization of Ambient Noise on Mars

Seismic noise recorded at the surface of Mars has been monitored since February 2019, using the InSight seismometers. This noise can reach −200 dB. It is 500 times lower than on Earth at night and it increases of 30 dB during the day. We analyze its polarization as a function of time and frequency in the band 0.03–1 Hz. We use the degree of polarization to extract signals with stable polarization independent of their amplitude and type of polarization. We detect polarized signals at all frequencies and all times. Glitches correspond to linear polarized signals which are more abundant during the night. For signals with elliptical polarization, the ellipse is in the horizontal plane below 0.3 Hz. In the 0.3-1Hz high frequency band (HF) and except in the evening, the ellipse is in the vertical plane and the major axis is tilted. While polarization azimuths are different in the two frequency bands, they both vary as a function of local hour and season. They are also correlated with wind direction, particularly during the daytime. We investigate possible aseismic and seismic origins of the polarized signals. Lander or tether noise can be discarded. Pressure fluctuations transported by wind may explain part of the HF polarization but not the tilt of the ellipse. This tilt can be obtained if the source is an acoustic emission coming from high altitude at critical angle. Finally, in the evening when the wind is low, the measured polarized signals may correspond to the seismic wavefield of the Mars background noise

Environmental and Parental Influences on Offspring Health and Growth in Great Tits (Parus major)

PMCID: PMC3728352This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins

The clustering of platelet glycoprotein receptors with cytosolic YxxL and YxxM motifs, including GPVI, CLEC-2 and PEAR1, triggers activation via phosphorylation of the conserved tyrosine residues and recruitment of the tandem SH2 (Src homology 2) domain effector proteins, Syk and PI 3-kinase. We have modelled the clustering of these receptors with monovalent, divalent and tetravalent soluble ligands and with transmembrane ligands based on the law of mass action using ordinary differential equations and agent-based modelling. The models were experimentally evaluated in platelets and transfected cell lines using monovalent and multivalent ligands, including novel nanobody-based divalent and tetravalent ligands, by fluorescence correlation spectroscopy. Ligand valency, receptor number, receptor dimerisation, receptor phosphorylation and a cytosolic tandem SH2 domain protein act in synergy to drive receptor clustering. Threshold concentrations of a CLEC-2-blocking antibody and Syk inhibitor act in synergy to block platelet aggregation. This offers a strategy for countering the effect of avidity of multivalent ligands and in limiting off-target effects