Body mass index and molecular subtypes of colorectal cancer

BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease. METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables. RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control). CONCLUSIONS: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome

Comparison of Image Registration Based Measures of Regional Lung Ventilation from Dynamic Spiral CT with Xe-CT

Purpose: Regional lung volume change as a function of lung inflation serves as an index of parenchymal and airway status as well as an index of regional ventilation and can be used to detect pathologic changes over time. In this article, we propose a new regional measure of lung mechanics --- the specific air volume change by corrected Jacobian. Methods: 4DCT and Xe-CT data sets from four adult sheep are used in this study. Nonlinear, 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration. Approximately 200 annotated anatomical points are used as landmarks to evaluate registration accuracy. Three different registration-based measures of regional lung mechanics are derived and compared: the specific air volume change calculated from the Jacobian (SAJ); the specific air volume change calculated by the corrected Jacobian (SACJ); and the specific air volume change by intensity change (SAI). Results: After registration, the mean registration error is on the order of 1 mm. For cubical ROIs in cubes with size 20 mm $\times$ 20 mm $\times$ 20 mm, the SAJ and SACJ measures show significantly higher correlation (linear regression, average $r^2=0.75$ and $r^2=0.82$) with the Xe-CT based measure of specific ventilation (sV) than the SAI measure. For ROIs in slabs along the ventral-dorsal vertical direction with size of 150 mm $\times$ 8 mm $\times$ 40 mm, the SAJ, SACJ, and SAI all show high correlation (linear regression, average $r^2=0.88$, $r^2=0.92$ and $r^2=0.87$) with the Xe-CT based sV without significant differences when comparing between the three methods. Conclusion: Given a deformation field by an image registration algorithm, significant differences between the SAJ, SACJ, and SAI measures were found at a regional level compared to the Xe-CT sV in four sheep that were studied

Development and Evaluation of an Undergraduate Science Communication Module

This paper describes the design and evaluation of an undergraduate final year science communication module for the Science Faculty at the University of East Anglia. The module focuses specifically on science communication and aims to bring an understanding of how science is disseminated to the public. Students on the module are made aware of the models surrounding science communication and investigate how the science culture interfaces with the public. During the module they learn how to adapt science concepts for different audiences and how to talk confidently about science to a lay-audience. Student motivation for module choice centres on the acquisition of transferable skills and students develop these skills through designing, running and evaluating a public outreach event at a school or in a public area. These transferable skills acquired include communication, interaction with different organisations such as museums and science centres, developing understanding of both the needs of different audiences and the importance of time management. They also develop skills relating to self-reflection and how to use this as a tool for future self development. The majority of students completing the module go on to further study, either a PhD, MSc or teacher training. The module can be sustained in its present formed if capped at 40 students, however it is recognised that to increase cohort size, further investment of faculty time and resources would be required

The kaon semileptonic form factor in Nf=2+1 domain wall lattice QCD with physical light quark masses

We present the first calculation of the kaon semileptonic form factor with sea and valence quark masses tuned to their physical values in the continuum limit of 2+1 flavour domain wall lattice QCD. We analyse a comprehensive set of simulations at the phenomenologically convenient point of zero momentum transfer in large physical volumes and for two different values of the lattice spacing. Our prediction for the form factor is f+(0)=0.9685(34)(14) where the first error is statistical and the second error systematic. This result can be combined with experimental measurements of K->pi decays for a determination of the CKM-matrix element for which we predict |Vus|=0.2233(5)(9) where the first error is from experiment and the second error from the lattice computation.Comment: 21 pages, 7 figures, 6 table

Aqua­(3-carboxybenzoato-κO 1)(nitrato-κO)(dipyrido[3,2-a:2′,3′-c]phenazine-κ2 N 4,N 5)copper(II)

The title complex, [Cu(C8H5O4)(NO3)(C18H10N4)(H2O)], was synthesized by reacting Cu(NO3)2, isophthalic acid and dipyridophenazine under hydro­thermal conditions. The CuII ion is in a slightly distorted square-pyramidal coordination environment. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds connect complex mol­ecules into chains along [001]

Arrhythmogenic Calmodulin Mutations Disrupt Intracellular Cardiomyocyte Ca\u3csup\u3e2+\u3c/sup\u3e Regulation by Distinct Mechanisms

BACKGROUND: Calmodulin (CaM) mutations have been identified recently in subjects with congenital long QT syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT), but the mechanisms responsible for these divergent arrhythmia-susceptibility syndromes in this context are unknown. We tested the hypothesis that LQTS-associated CaM mutants disrupt Ca2+ homeostasis in developing cardiomyocytes possibly by affecting either late Na current or Ca2+-dependent inactivation of L-type Ca2+ current. METHODS AND RESULTS: We coexpressed CaM mutants with the human cardiac Na channel (NaV1.5) in tsA201 cells, and we used mammalian fetal ventricular cardiomyocytes to investigate LQTS- and CPVT-associated CaM mutations (LQTS- and CPVT-CaM). LQTS-CaM mutants do not consistently affect L-type Na current in heterologous cells or native cardiomyocytes, suggesting that the Na channel does not contribute to LQTS pathogenesis in the context of CaM mutations. LQTS-CaM mutants (D96V, D130G, F142L) impaired Ca2+-dependent inactivation, whereas the CPVT-CaM mutant N54I had no effect on Ca2+-dependent inactivation. LQTS-CaM mutants led to loss of Ca2+-transient entrainment with the rank order from greatest to least effect: CaM-D130G~CaM-D96V\u3e\u3eCaM-F142L. This rank order follows measured Ca2+-CaM affinities for wild-type and mutant CaM. Acute isoproterenol restored entrainment for CaM-130G and CaM-D96V but caused irreversible cytosolic Ca2+ overload for cells expressing a CPVT-CaM mutant. CONCLUSIONS: CaM mutations associated with LQTS may not affect L-type Na+ current but may evoke defective Ca2+-dependent inactivation of L-type Ca2+ current

Thermochronologic constraints on the late Cenozoic exhumation history of the Gurla Mandhata metamorphic core complex, Southwestern Tibet

This is the publisher's version, also available electronically from http://onlinelibrary.wiley.com/doi/10.1002/2013TC003302/abstractHow the Tibetan plateau is geodynamically linked to the Himalayas is a topic receiving considerable attention. The Karakoram fault plays key roles in describing the structural relationship between southern Tibet and the Himalayas. In particular, considerable debate exists at the southeastern end of the Karakoram fault, where its role is interpreted in two different ways. One interpretation states that slip along the dextral Karakoram fault extends eastward along the Indus-Yalu suture zone, bypassing the Himalayas. The other interprets that fault slip is fed southward into the Himalayan thrust belt along the Gurla Mandhata detachment (GMD). To evaluate these competing models, the late Miocene history of the GMD was reconstructed from thermokinematic modeling of zircon (U-Th)/He data. Three east-west transects reveal rapid cooling of the GMD footwall from 8.0 ± 1.3 Ma to 2.6 ± 0.7 Ma. Model simulations show a southward decrease in slip magnitude and rate along the GMD. In the north, initiation of the GMD range between 14 and 11 Ma with a mean fault slip rate of 5.0 ± 0.9 mm/yr. The central transect shows an initiation age from 14 to 11 Ma with a mean fault slip rate of 3.3 ± 0.6 mm/yr. In the south, initiation began between 15 and 8 Ma with a mean fault slip rate of 3.2 ± 1.6 mm/yr. The initiation ages and slip rates match the Karakoram fault across several timescales, supporting the idea that the two are kinematically linked. Specifically, the data are consistent with the GMD acting as an extensional stepover, with slip transferred southward into the Himalayas of western Nepal

Seroepidemiology of Human Enterovirus 71, Singapore

Human enterovirus 71 has caused outbreaks in many parts of the world, especially Southeast Asia, with some fatal cases. The epidemiology of this viral infection is not well understood. We conducted a serologic survey in Singapore children, and the results indicate that infection occurs largely in preschool settings

Optimal treatment allocations in space and time for on-line control of an emerging infectious disease

A key component in controlling the spread of an epidemic is deciding where, whenand to whom to apply an intervention.We develop a framework for using data to informthese decisionsin realtime.We formalize a treatment allocation strategy as a sequence of functions, oneper treatment period, that map up-to-date information on the spread of an infectious diseaseto a subset of locations where treatment should be allocated. An optimal allocation strategyoptimizes some cumulative outcome, e.g. the number of uninfected locations, the geographicfootprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategyfor an emerging infectious disease is challenging because spatial proximity induces interferencebetween locations, the number of possible allocations is exponential in the number oflocations, and because disease dynamics and intervention effectiveness are unknown at outbreak.We derive a Bayesian on-line estimator of the optimal allocation strategy that combinessimulation–optimization with Thompson sampling.The estimator proposed performs favourablyin simulation experiments. This work is motivated by and illustrated using data on the spread ofwhite nose syndrome, which is a highly fatal infectious disease devastating bat populations inNorth America