Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.

BackgroundLobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.MethodsIn all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.ResultsOut of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.ConclusionOur study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection

Lectures on Linear Stability of Rotating Black Holes

These lecture notes are concerned with linear stability of the non-extreme Kerr geometry under perturbations of general spin. After a brief review of the Kerr black hole and its symmetries, we describe these symmetries by Killing fields and work out the connection to conservation laws. The Penrose process and superradiance effects are discussed. Decay results on the long-time behavior of Dirac waves are outlined. It is explained schematically how the Maxwell equations and the equations for linearized gravitational waves can be decoupled to obtain the Teukolsky equation. It is shown how the Teukolsky equation can be fully separated to a system of coupled ordinary differential equations. Linear stability of the non-extreme Kerr black hole is stated as a pointwise decay result for solutions of the Cauchy problem for the Teukolsky equation. The stability proof is outlined, with an emphasis on the underlying ideas and methods.Comment: 25 pages, LaTeX, 3 figures, lectures given at first DOMOSCHOOL in July 2018, minor improvements (published version

Association between COPD exacerbations and lung function decline during maintenance therapy

Acknowledgements: Writing and editorial support was provided by Dr Julia Granerod, supported by the Observational and Pragmatic Research Institute Pte. Ltd (OPRI). Funding: This study was funded by AstraZeneca.Data availability statement: Data may be obtained from a third party and are not publicly available. The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink (www.cprd.com) and the Optimum Patient Care Research Database (www.opcrd.co.uk). The CPRD has broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 5/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The authors do not have permission to give public access to the study dataset; researchers may request access to CPRD or OPCRD data for their own purposes. Access to CPRD can be made via the CPRD website (https://www.cprd.com/researcher/) or via the enquiries email enquiries@cprd. com. Access to OCPRD can be made via the OCPRD website(https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email [email protected]. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS19879).Peer reviewedPublisher PD

Kerr-AdS and its Near-horizon Geometry: Perturbations and the Kerr/CFT Correspondence

We investigate linear perturbations of spin-s fields in the Kerr-AdS black hole and in its near-horizon geometry (NHEK-AdS), using the Teukolsky master equation and the Hertz potential. In the NHEK-AdS geometry we solve the associated angular equation numerically and the radial equation exactly. Having these explicit solutions at hand, we search for linear mode instabilities. We do not find any (non-)axisymmetric instabilities with outgoing boundary conditions. This is in agreement with a recent conjecture relating the linearized stability properties of the full geometry with those of its near-horizon geometry. Moreover, we find that the asymptotic behaviour of the metric perturbations in NHEK-AdS violates the fall-off conditions imposed in the formulation of the Kerr/CFT correspondence (the only exception being the axisymmetric sector of perturbations).Comment: 26 pages. 4 figures. v2: references added. matches published versio

A scalar field condensation instability of rotating anti-de Sitter black holes

Near-extreme Reissner-Nordstrom-anti-de Sitter black holes are unstable against the condensation of an uncharged scalar field with mass close to the Breitenlohner-Freedman bound. It is shown that a similar instability afflicts near-extreme large rotating AdS black holes, and near-extreme hyperbolic Schwarzschild-AdS black holes. The resulting nonlinear hairy black hole solutions are determined numerically. Some stability results for (possibly charged) scalar fields in black hole backgrounds are proved. For most of the extreme black holes we consider, these demonstrate stability if the ``effective mass" respects the near-horizon BF bound. Small spherical Reissner-Nordstrom-AdS black holes are an interesting exception to this result.Comment: 34 pages; 13 figure

An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints

In this work, we introduce an algorithm to compute the derivatives of physical observables along the constrained subspace when flexible constraints are imposed on the system (i.e., constraints in which the hard coordinates are fixed to configuration-dependent values). The presented scheme is exact, it does not contain any tunable parameter, and it only requires the calculation and inversion of a sub-block of the Hessian matrix of second derivatives of the function through which the constraints are defined. We also present a practical application to the case in which the sought observables are the Euclidean coordinates of complex molecular systems, and the function whose minimization defines the constraints is the potential energy. Finally, and in order to validate the method, which, as far as we are aware, is the first of its kind in the literature, we compare it to the natural and straightforward finite-differences approach in three molecules of biological relevance: methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio

Appointing Women to Boards: Is There a Cultural Bias?

Companies that are serious about corporate governance and business ethics are turning their attention to gender diversity at the most senior levels of business (Institute of Business Ethics, Business Ethics Briefing 21:1, 2011). Board gender diversity has been the subject of several studies carried out by international organizations such as Catalyst (Increasing gender diversity on boards: Current index of formal approaches, 2012), the World Economic Forum (Hausmann et al., The global gender gap report, 2010), and the European Board Diversity Analysis (Is it getting easier to find women on European boards? 2010). They all lead to reports confirming the overall relatively low proportion of women on boards and the slow pace at which more women are being appointed. Furthermore, the proportion of women on corporate boards varies much across countries. Based on institutional theory, this study hypothesizes and tests whether this variation can be attributed to differences in cultural settings across countries. Our analysis of the representation of women on boards for 32 countries during 2010 reveals that two cultural characteristics are indeed associated with the observed differences. We use the cultural dimensions proposed by Hofstede (Culture’s consequences: International differences in work-related values, 1980) to measure this construct. Results show that countries which have the greatest tolerance for inequalities in the distribution of power and those that tend to value the role of men generally exhibit lower representations of women on boards

A discrete random model describing bedrock profile abrasion

We use a simple, collision-based, discrete, random abrasion model to compute the profiles for the stoss faces in a bedrock abrasion process. The model is the discrete equivalent of the generalized version of a classical, collision based model of abrasion. Three control parameters (which describe the average size of the colliding objects, the expected direction of the impacts and the average volume removed from the body due to one collision) are sufficient for realistic predictions. Our computations show the robust emergence of steady state shapes, both the geometry and the time evolution of which shows good quantitative agreement with laboratory experiments.Comment: 9 pages, 6 figure