Regulation of Lean Mass, Bone Mass, and Exercise Tolerance by the Central Melanocortin System

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity

Codeine Addiction and Internet Forum Use and Support: Qualitative Netnographic Study

Background: The use of codeine as an analgesic is well-recognized, but there are increasing concerns that for some individuals continued use may lead to misuse, dependence, and fatalities. Research suggests that those affected may represent a hard-to-reach group who do not engage with formal treatment services. Objective: This study sought to explore the experiences of people with self-reported addiction to codeine and, specifically, how a social media forum is used to communicate with others about this issue. Methods: Using a qualitative netnographic methodology, the social media forum Mumsnet was used, with permission, and searches were undertaken in 2016 of any posts that related to codeine and addiction. A total of 95 relevant posts were identified; a purposive sample of 25 posts was selected to undertake subsequent six-stage thematic analysis and development of emerging themes. These 25 posts were posted between 2003 and 2016 and comprised 757 individual posts. Results: Individuals created posts to actively request help in relation to usually their own, but occasionally their partner’s or relative’s, problems relating to codeine use and self-reported “addiction.” Varying levels of detail were provided in narratives of problematic codeine use. There were both positive and negative descriptions of side effects emerging, problems experiencing withdrawal, and failed attempts to discontinue codeine use. Mainly positive and supportive responses to posts were identified from those with either self-reported health profession experience or lay respondents, who often drew on their own experiences of similar problems. Treatment advice emerged in two main ways, either as signposting to formal health services or to informal approaches and often anecdotal advice about how to taper or use cold turkey techniques. Some posts were more critical of the original poster, and arguments and challenges to advice were not uncommon. Shame and stigma were often associated with users’ posts and, while there was a desire to receive support and treatment advice in this forum, users often wanted to keep their codeine use hidden in other aspects of their lives. Distinctly different views emerged as to whether responsibility lay with prescribers or patients. Some users expressed anger toward doctors and their prescribing practices. Conclusions: This study provides a unique insight into how a public internet forum is used by individuals to confirm and seek support about problematic codeine use and of the ways others respond. The pseudonymous use of internet forums for such information and variation in treatment options suggested by often lay respondents suggest that increased formal support and awareness about codeine addiction are needed. There may be opportunities for providing further support directly on such online forums. Improvements in prescribing codeine and in the over-the-counter supply of codeine are required to prevent problematic use from occurring

Extreme Technicolor & The Walking Critical Temperature

We map the phase diagram of gauge theories of fundamental interactions in the flavor-temperature plane using chiral perturbation theory to estimate the relation between the pion decaying constant and the critical temperature above which chiral symmetry is restored. We then investigate the impact of our results on models of dynamical electroweak symmetry breaking and therefore on the electroweak early universe phase transition.Comment: RevTeX, 18 pages, 3 figure

Observation of Bose-Einstein Condensation in a Strong Synthetic Magnetic Field

Extensions of Berry's phase and the quantum Hall effect have led to the discovery of new states of matter with topological properties. Traditionally, this has been achieved using gauge fields created by magnetic fields or spin orbit interactions which couple only to charged particles. For neutral ultracold atoms, synthetic magnetic fields have been created which are strong enough to realize the Harper-Hofstadter model. Despite many proposals and major experimental efforts, so far it has not been possible to prepare the ground state of this system. Here we report the observation of Bose-Einstein condensation for the Harper-Hofstadter Hamiltonian with one-half flux quantum per lattice unit cell. The diffraction pattern of the superfluid state directly shows the momentum distribution on the wavefuction, which is gauge-dependent. It reveals both the reduced symmetry of the vector potential and the twofold degeneracy of the ground state. We explore an adiabatic many-body state preparation protocol via the Mott insulating phase and observe the superfluid ground state in a three-dimensional lattice with strong interactions.Comment: 6 pages, 5 figures. Supplement: 6 pages, 4 figure

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral bloo

Requirements Analysis for an Open Research Knowledge Graph

Current science communication has a number of drawbacks and bottlenecks which have been subject of discussion lately: Among others, the rising number of published articles makes it nearly impossible to get an overview of the state of the art in a certain field, or reproducibility is hampered by fixed-length, document-based publications which normally cannot cover all details of a research work. Recently, several initiatives have proposed knowledge graphs (KGs) for organising scientific information as a solution to many of the current issues. The focus of these proposals is, however, usually restricted to very specific use cases. In this paper, we aim to transcend this limited perspective by presenting a comprehensive analysis of requirements for an Open Research Knowledge Graph (ORKG) by (a) collecting daily core tasks of a scientist, (b) establishing their consequential requirements for a KG-based system, (c) identifying overlaps and specificities, and their coverage in current solutions. As a result, we map necessary and desirable requirements for successful KG-based science communication, derive implications and outline possible solutions.Comment: Accepted for publishing in 24th International Conference on Theory and Practice of Digital Libraries, TPDL 202

The influences and consequences of being digitally connected and/or disconnected to travellers

© 2017, The Author(s).Technological progress and tourism have worked in tandem for many years. Connectivity is the vehicle that drove the goal of technologically enhanced tourism experiences forward. This study, through an exploratory qualitative research identifies the factors that boost and/or distract travellers from obtaining a digitally enhanced tourism experience. Four factors can boost and/or distract travellers from being connected: (1) hardware and software, (2) needs and contexts, (3) openness to usage, and (4) supply and provision of connectivity. The research also analyses the positive and/or negative consequences that arise from being connected or disconnected. A Connected/Disconnected Consequences Model illustrates five forms of positive and/or negative consequences: (1) availability, (2) communication, (3) information obtainability, (4) time consumption, and (5) supporting experiences. A better understanding of the role and consequence of connectivity during the trip can enhance traveller experience

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration