Anticholinergic drug burden tools/scales and adverse outcomes in different clinical settings: a systematic review of reviews

Background: Cumulative anticholinergic exposure (anticholinergic burden) has been linked to a number of adverse outcomes. To conduct research in this area, an agreed approach to describing anticholinergic burden is needed. Objective: This review set out to identify anticholinergic burden scales, to describe their rationale, the settings in which they have been used and the outcomes associated with them. Methods: A search was performed using the Healthcare Databases Advanced Search of MEDLINE, EMBASE, Cochrane, CINAHL and PsycINFO from inception to October 2016 to identify systematic reviews describing anticholinergic burden scales or tools. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. The final selection of reviews was critically appraised using the ROBIS tool and pre-defined data were extracted; the primary data of interest were the anticholinergic burden scales or tools used. Results: Five reviews were identified for analysis containing a total of 62 original articles. Eighteen anticholinergic burden scales or tools were identified with variation in their derivation, content and how they quantified the anticholinergic activity of medications. The Drug Burden Index was the most commonly used scale or tool in community and database studies, while the Anticholinergic Risk Scale was used more frequently in care homes and hospital settings. The association between anticholinergic burden and clinical outcomes varied by index and study. Falls and hospitalisation were consistently found to be associated with anticholinergic burden. Mortality, delirium, physical function and cognition were not consistently associated. Conclusions: Anticholinergic burden scales vary in their rationale, use and association with outcomes. This review showed that the concept of anticholinergic burden has been variably defined and inconsistently described using a number of indices with different content and scoring. The association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established

Cancer stem cell metabolism: A potential target for cancer therapy

© 2016 The Author(s). Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells. This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

Peer reviewe

Measurement of the rapidity and transverse momentum distributions of Z bosons in pp collisions at √(s)=7 TeV

Measurements of the normalized rapidity (y) and transverse-momentum (qT) distributions of Drell–Yan muon and electron pairs in the Z-boson mass region (60<Mℓℓ<120  GeV) are reported. The results are obtained using a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, collected by the CMS experiment at the Large Hadron Collider (LHC), corresponding to an integrated luminosity of 36  pb-1. The distributions are measured over the ranges |y|<3.5 and qT<600  GeV and compared with quantum chromodynamics (QCD) calculations using recent parton distribution functions to model the momenta of the quarks and gluons in the protons. Overall agreement is observed between the models and data for the rapidity distribution, while no single model describes the Z transverse-momentum distribution over the full range

Indications of suppression of excited Υ states in Pb-Pb collisions at √sNN = 2.76TeV

This is the pre-print version of the Published Article which can be accessed from the link below.A comparison of the relative yields of Υ resonances in the μ+μ- decay channel in Pb-Pb and pp collisions at a center-of-mass energy per nucleon pair of 2.76 TeV is performed with data collected with the CMS detector at the LHC. Using muons of transverse momentum above 4  GeV/c and pseudorapidity below 2.4, the double ratio of the Υ(2S) and Υ(3S) excited states to the Υ(1S) ground state in Pb-Pb and pp collisions, [Υ(2S+3S)/Υ(1S)]Pb-Pb/[Υ(2S+3S)/Υ(1S)]pp, is found to be 0.31-0.15+0.19(stat)±0.03(syst). The probability to obtain the measured value, or lower, if the true double ratio is unity, is calculated to be less than 1%

Search for new physics with a monojet and missing transverse energy in pp collisions at √s=7 TeV

This is the pre-print version of the Published Article which can be accessed at the link below.A study of events with missing transverse energy and an energetic jet is performed using pp collision data at a center-of-mass energy of 7 TeV. The data were collected by the CMS detector at the LHC, and correspond to an integrated luminosity of 36  pb-1. An excess of these events over standard model contributions is a signature of new physics such as large extra dimensions and unparticles. The number of observed events is in good agreement with the prediction of the standard model, and significant extension of the current limits on parameters of new physics benchmark models is achieved

Weak and Straddling Secondary Nicotinic Synapses Can Drive Firing in Rat Sympathetic Neurons and Thereby Contribute to Ganglionic Amplification

Interactions between nicotinic excitatory postsynaptic potentials (EPSPs) critically determine whether paravertebral sympathetic ganglia behave as simple synaptic relays or as integrative centers that amplify preganglionic activity. Synaptic connectivity in this system is characterized by an n + 1 pattern of convergence, where each ganglion cell receives one very strong primary input and a variable number (n) of weak secondary inputs that are subthreshold in strength. To test whether pairs of secondary nicotinic EPSPs can summate to fire action potentials (APs) and thus mediate ganglionic gain in the rat superior cervical ganglion, we recorded intracellularly at 34°C and used graded presynaptic stimulation to isolate individual secondary synapses. Weak EPSPs in 40 of 53 neurons had amplitudes of 0.5–7 mV (mean 3.5 ± 0.3 mV). EPSPs evoked by paired pulse stimulation were either depressing (n = 10), facilitating (n = 9), or borderline (n = 10). In 15 of 29 cells, pairs of weak secondary EPSPs initiated spikes when elicited within a temporal window <20 ms, irrespective of EPSP amplitude or paired pulse response type. In six other neurons, we observed novel secondary EPSPs that were strong enough to straddle spike threshold without summation. At stimulus rates <1 Hz straddling EPSPs appeared suprathreshold in strength. However, their limited ability to drive firing could be blocked by the afterhyperpolarization following an AP. When viewed in a computational context, these findings support the concept that weak and straddling secondary nicotinic synapses enable mammalian sympathetic ganglia to behave as use-dependent amplifiers of preganglionic activity

Relative Modification of Prompt psi(2S) and J/psi Yields from pp to PbPb Collisions at root(S)(NN)=5.02 TeV

Peer reviewe

Long-range and short-range dihadron angular correlations in central PbPb collisions at √sNN=2.76 TeV

This is the pre-print version of the Published Article, which can be accessed from the link below.First measurements of dihadron correlations for charged particles are presented for central PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76TeV over a broad range in relative pseudorapidity ( ) and the full range of relative azimuthal angle ( ). The data were collected with the CMS detector, at the LHC. A broadening of the away-side ( ) azimuthal correlation is observed at all , as compared to the measurements in pp collisions. Furthermore, long-range dihadron correlations in are observed for particles with similar values. This phenomenon, also known as the \ridge", persists up to at least j j = 4. For particles with transverse momenta (pT) of 2-4 GeV/c, the ridge is found to be most prominent when these particles are correlated with particles of pT = 2-6 GeV/c, and to be much reduced when paired with particles of pT = 10-12 GeV/c