Increased IKKα Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors

Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKKα expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKKα in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKKα transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-α6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKKα-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKKα in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-α6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKKα skin tumors

Trends in incidence, mortality and survival in women with breast cancer from 1985 to 2012 in Granada, Spain: a population-based study

The incidence of breast cancer has increased since the 1970s. Despite favorable trends in prognosis, the role of changes in clinical practice and the introduction of screening remain controversial. We examined breast cancer trends to shed light on their determinants Overall, age-adjusted (European Standard Population) incidence rates increased from 48.0 cases × 100,000 women in 1985–1989 to 83.4 in 2008–2012, with an annual percentage change (APC) of 2.5% (95%CI, 2.1–2.9) for 1985–2012. The greatest increase was in women younger than 40 years (APC 3.5, 95%CI, 2.4–4.8). For 2000–2012 the incidence trend increased only for stage I tumors (APC 3.8, 95%CI, 1.9–5.8). Overall age-adjusted breast cancer mortality decreased (APC − 1, 95%CI, − 1.4 – − 0.5), as did mortality in the 50–69 year age group (APC − 1.3, 95%CI, − 2.2 – − 0.4). Age-standardized net survival increased from 67.5% at 5 years in 1985–1989 to 83.7% in 2010–2012. All age groups younger than 70 years showed a similar evolution. Five-year net survival rates were 96.6% for patients with tumors diagnosed in stage I, 88.2% for stage II, 62.5% for stage III and 23.3% for stage IV. Breast cancer incidence is increasing – a reflection of the evolution of risk factors and increasing diagnostic pressure. After screening was introduced, the incidence of stage I tumors increased, with no decrease in the incidence of more advanced stages. Reductions were seen for overall mortality and mortality in the 50–69 year age group, but no changes were found after screening implementation. Survival trends have evolved favorably except for the 70–84 year age group and for metastatic tumors.This study was supported by a grant from the Acción Estratégica en Salud plan for the High Resolution Project on Prognosis and Care of Cancer Patients (No. AC14/00036) awarded by the Spanish Ministry of Economy and Competitiveness and co-funded by the European Regional Development Fund (ERDF)

Optical and infrared flares from a transient Galactic soft gamma-ray repeater

Soft gamma-ray repeaters (SGRs) are a rare type of gamma-ray transient sources that are ocasionally detected as bursts in the high-energy sky. They are thought to be produced by magnetars, young neutron stars with very strong magnetic fields of the order of 10^(14-15) G. Only three such objects are known in our Galaxy, and a fourth one is associated with the supernova remnant N49 in the Large Magellanic Cloud. In none of these cases has an optical counterpart to either the gamma-ray flares or the quiescent source been identified. Here we present multi-wavelength observations of a puzzling source, SWIFT J195509+261406, for which we detected more than 40 flaring episodes in the optical band over a time span of 3 days, plus a faint infrared flare 11 days later, after which it returned to quiescence. We propose that SWIFT J195509+261406 is a member of a subgroup of SGRs for which the long-term X-ray emission is transient in nature. Furthermore, it is the first SGR for which bursts have been detected in the optical and near-infrared bands and maybe the link between the "persistent" SGRs and the dim isolated neutron stars.Comment: Version submitted to Nature on 31 Jan 2008. A substantially revised version of this work has been published in Nature, vol. 455 issue 7212 pp 506-509 under the title "Flares from a Galactic magnetar suggest a missing link to dim isolated neutron stars

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

A new calibration method for charm jet identification validated with proton-proton collision events at √s = 13 TeV

ArXiv ePrint: 2111.03027Copyright © 2022 CERN for the benefit of the CMS collaboration. Many measurements at the LHC require efficient identification of heavy-flavour jets, i.e. jets originating from bottom (b) or charm (c) quarks. An overview of the algorithms used to identify c jets is described and a novel method to calibrate them is presented. This new method adjusts the entire distributions of the outputs obtained when the algorithms are applied to jets of different flavours. It is based on an iterative approach exploiting three distinct control regions that are enriched with either b jets, c jets, or light-flavour and gluon jets. Results are presented in the form of correction factors evaluated using proton-proton collision data with an integrated luminosity of 41.5 fb-1 at  √s = 13 TeV, collected by the CMS experiment in 2017. The closure of the method is tested by applying the measured correction factors on simulated data sets and checking the agreement between the adjusted simulation and collision data. Furthermore, a validation is performed by testing the method on pseudodata, which emulate various mismodelling conditions. The calibrated results enable the use of the full distributions of heavy-flavour identification algorithm outputs, e.g. as inputs to machine-learning models. Thus, they are expected to increase the sensitivity of future physics analyses.SCOAP

Search for supersymmetry in final states with two or three soft leptons and missing transverse momentum in proton-proton collisions at root s=13 TeV

ArXiv ePrint: 2111.06296 (https://arxiv.org/abs/2111.06296).Copyright © 2022 CERN, for the benefit of the CMS Collaboration. A search for supersymmetry in events with two or three low-momentum leptons and missing transverse momentum is performed. The search uses proton-proton collisions at s√ = 13 TeV collected in the three-year period 2016–2018 by the CMS experiment at the LHC and corresponding to an integrated luminosity of up to 137 fb−1. The data are found to be in agreement with expectations from standard model processes. The results are interpreted in terms of electroweakino and top squark pair production with a small mass difference between the produced supersymmetric particles and the lightest neutralino. For the electroweakino interpretation, two simplified models are used, a wino-bino model and a higgsino model. Exclusion limits at 95% confidence level are set on χ∼02/χ∼±1 masses up to 275 GeV for a mass difference of 10 GeV in the wino-bino case, and up to 205(150) GeV for a mass difference of 7.5 (3) GeV in the higgsino case. The results for the higgsino are further interpreted using a phenomenological minimal supersymmetric standard model, excluding the higgsino mass parameter μ up to 180 GeV with the bino mass parameter M1 at 800 GeV. In the top squark interpretation, exclusion limits are set at top squark masses up to 540 GeV for four-body top squark decays and up to 480 GeV for chargino-mediated decays with a mass difference of 30 GeV.SCOAP3