Incident cancer burden attributable to excess body mass index in 30 European countries

Excess adiposity is associated with increased risks of developing adult malignancies. To inform public health policy and guide further research, the incident cancer burden attributable to excess body mass index (BMI >or= 25 kg/m(2)) across 30 European countries were estimated. Population attributable risks (PARs) were calculated using European- and gender-specific risk estimates from a published meta-analysis and gender-specific mean BMI estimates from a World Health Organization Global Infobase. Country-specific numbers of new cancers were derived from Globocan2002. A ten-year lag-period between risk exposure and cancer incidence was assumed and 95% confidence intervals (CI) were estimated in Monte Carlo simulations. In 2002, there were 2,171,351 new all cancer diagnoses in the 30 countries of Europe. Estimated PARs were 2.5% (95% CI 1.5-3.6%) in men and 4.1% (2.3-5.9%) in women. These collectively corresponded to 70,288 (95% CI 40,069-100,668) new cases. Sensitivity analyses revealed estimates were most influenced by the assumed shape of the BMI distribution in the population and cancer-specific risk estimates. In a scenario analysis of a plausible contemporary (2008) population, the estimated PARs increased to 3.2% (2.1-4.3%) and 8.6% (5.6-11.5%), respectively, in men and women. Endometrial, post-menopausal breast and colorectal cancers accounted for 65% of these cancers. This analysis quantifies the burden of incident cancers attributable to excess BMI in Europe. The estimates reported here provide a baseline for future modelling, and underline the need for research into interventions to control weight in the context of endometrial, breast and colorectal cancer.

Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies

BACKGROUND: Excess bodyweight, expressed as increased body-mass index (BMI), is associated with the risk of some common adult cancers. We did a systematic review and meta-analysis to assess the strength of associations between BMI and different sites of cancer and to investigate differences in these associations between sex and ethnic groups. METHODS: We did electronic searches on Medline and Embase (1966 to November 2007), and searched reports to identify prospective studies of incident cases of 20 cancer types. We did random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of cancer associated with a 5 kg/m2 increase in BMI. FINDINGS: We analysed 221 datasets (141 articles), including 282,137 incident cases. In men, a 5 kg/m2 increase in BMI was strongly associated with oesophageal adenocarcinoma (RR 1.52, p<0.0001) and with thyroid (1.33, p=0.02), colon (1.24, p<0.0001), and renal (1.24, p <0.0001) cancers. In women, we recorded strong associations between a 5 kg/m2 increase in BMI and endometrial (1.59, p<0.0001), gallbladder (1.59, p=0.04), oesophageal adenocarcinoma (1.51, p<0.0001), and renal (1.34, p<0.0001) cancers. We noted weaker positive associations (RR <1.20) between increased BMI and rectal cancer and malignant melanoma in men; postmenopausal breast, pancreatic, thyroid, and colon cancers in women; and leukaemia, multiple myeloma, and non-Hodgkin lymphoma in both sexes. Associations were stronger in men than in women for colon (p<0.0001) cancer. Associations were generally similar in studies from North America, Europe and Australia, and the Asia-Pacific region, but we recorded stronger associations in Asia-Pacific populations between increased BMI and premenopausal (p=0.009) and postmenopausal (p=0.06) breast cancers. INTERPRETATION: Increased BMI is associated with increased risk of common and less common malignancies. For some cancer types, associations differ between sexes and populations of different ethnic origins. These epidemiological observations should inform the exploration of biological mechanisms that link obesity with cancer.

Dimension Distortion by Sobolev Mappings in Foliated Metric Spaces

We quantify the extent to which a supercritical Sobolev mapping can increase the dimension of subsets of its domain, in the setting of metric measure spaces supporting a Poincaré inequality. We show that the set of mappings that distort the dimensions of sets by the maximum possible amount is a prevalent subset of the relevant function space. For foliations of a metric space X defined by a David–Semmes regular mapping Π : X → W, we quantitatively estimate, in terms of Hausdorff dimension in W, the size of the set of leaves of the foliation that are mapped onto sets of higher dimension. We discuss key examples of such foliations, including foliations of the Heisenberg group by left and right cosets of horizontal subgroups.

The effect of projections on dimension in the Heisenberg group

We prove analogs of classical almost sure dimension theorems for Euclidean projection mappings in the first Heisenberg group, equipped with a sub-Riemannian metric.

Frequency of Sobolev and quasiconformal dimension distortion

We study Hausdorff and Minkowski dimension distortion for images of generic affine subspaces of Euclidean space under Sobolev and quasiconformal maps. For a supercritical Sobolev map f defined on a domain in RnRn, we estimate from above the Hausdorff dimension of the set of affine subspaces parallel to a fixed m-dimensional linear subspace, whose image under f has positive HαHα measure for some fixed α>mα>m. As a consequence, we obtain new dimension distortion and absolute continuity statements valid for almost every affine subspace. Our results hold for mappings taking values in arbitrary metric spaces, yet are new even for quasiconformal maps of the plane. We illustrate our results with numerous examples.

Modulus and Poincaré Inequalities on Non-Self-Similar Sierpiński Carpets

A carpet is a metric space homeomorphic to the Sierpiński carpet. We characterize, within a certain class of examples, non-self-similar carpets supporting curve families of nontrivial modulus and supporting Poincaré inequalities. Our results yield new examples of compact doubling metric measure spaces supporting Poincaré inequalities: these examples have no manifold points, yet embed isometrically as subsets of Euclidean space.

Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells

Human pluripotent stem cells are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations: projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism, and epilepsy. Here, we demonstrate the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes, and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin- and somatostatin-expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient for modeling human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology.

"A Room of One's Own": Reale und mentale Innenräume weiblicher Selbstbestimmung im spätmittelalterlichen England

Frauen werden im englischen Spätmittelalter auf den Innenraum von Haus und Kirche verwiesen. Wie sie diese Räume nutzten und kreativ (um-)gestalteten und auf welche Weise es ihnen gelang, reale Räume mental zu transgredieren und durch mentale Innenräume auszuwechseln, zeigt diese Arbeit. Dabei wird Raum - in Anlehnung an Giddens’ Theory of Structuration und den poststrukturalistischen Ansatz der Archäologie - als sowohl wirkmächtig als auch verschieden interpretierbar und transformierbar verstanden. Der Rückzug in den mentalen Innenraum führte im Extremfall dazu, daß neben der realen eine zweite Existenz aufgebaut wurde. Beide Existenzweisen konnten, wie insbesondere an den Biographien von Margaret Beaufort sowie Cicely und Margaret von York ablesbar ist, problemlos nebeneinander bestehen oder - wie am Beispiel von Margery Kempe gezeigt wird - so unvereinbar miteinander sein, daß gesellschaftliche Sanktionen die Folge waren.