699 research outputs found
Discordance in latent tuberculosis (TB) tests results in end stage renal disease patients
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2019
- Field of study
OBJECTIVES:
This natural experiment was designed to assess the impact of exposure to an active
case of tuberculosis in a group of immunosuppressed individual, with end stage renal disease
over an extended follow up.
STUDY DESIGN:
Close contacts of people with sputum smear positive Mycobacterium tuberculosis
are at high risk of infection, particularly immunosuppressed individuals. An infectious
tuberculosis health care worker worked in a renal dialysis unit for a month before diagnosis, with
104 renal dialysis patients exposed for â„8 hours.
METHODS:
Patients were informed and invited for screening 8-10 weeks post-exposure. They
either underwent standard two-step assessment with tuberculin skin test (TST) and
QuantiFERONÂź-TB Gold [Cellestis GmbH] (QFN) interferon gamma release assay (IGRA); or
following consent, enrolled in a study where these two tests were performed simultaneously
with T-SPOTÂź-TB [Oxford Immunotec Ltd] (TSPOT). Patients within the study were followed up for
two years from exposure;with QFN and TSPOT repeated at months 3 and 6 from first testing
RESULTS:
Of 104 exposed individuals, 75 enrolled in the study. There was a high degree of
discordance between QFN, TSPOT and TST. This was seen at both the first timepoint, and also
over time in subjects who were re-tested. No patients had active TB at baseline testing. None
received treatment for latent TB infection. Over the following two years, no-one developed TB
disease.
CONCLUSION:
This study suggests there is a low risk of progression to active TB in low incidence
countries even in high risk groups. This plus the degree of test result discordance emphasises the
complexities of managing TB in such settings, as it is unclear which of these tests, if any, provides
the best diagnostic accuracy
A pilot study of an integrated mental health, social and medical model for diabetes care in an innerâcity setting: three dimensions for diabetes (3DFD)
- Author
- Atlantis E
- Concato J
- Coventry P
- Doherty AM
- Fisher L
- Fisher L
- Gary TL
- Glazier RH
- Gonzalez JS
- Heinze G
- Hex N
- HippisleyâCox J
- Hopkins D
- Ismail K
- Joint Formulary Committee
- Katon W
- Katon WJ
- Killaspy H
- Lustman PJ
- Mihaylova B
- Mitchell C
- Osborn CY
- Petrak F
- Plotnikoff RC
- Riste L
- Riva M
- Roy T
- Salisbury C
- Spitzer RL
- Spitzer RL
- Tadros G
- Zhuo X
- Publication venue
- 'Wiley'
- Publication date
- 01/02/2019
- Field of study
Aims
We examined the effectiveness of a service innovation, Three Dimensions for Diabetes (3DFD), that consisted of a referral to an integrated mental health, social care and diabetes treatment model, compared with usual care in improving biomedical and health economic outcomes.
Methods
Using a nonârandomized control design, the 3DFD model was offered in two innerâcity boroughs in London, UK, where diabetes health professionals could refer adult residents with diabetes, suboptimal glycaemic control [HbA1c â„ 75 mmol/mol (â„ 9.0%)] and mental health and/or social problems. In the usual care group, there was no referral pathway and anonymized data on individuals with HbA1c â„ 75 mmol/mol (â„ 9.0%) were collected from primary care records. Change in HbA1c from baseline to 12 months was the primary outcome, and change in healthcare costs and biomedical variables were secondary outcomes.
Results
3DFD participants had worse glycaemic control and higher healthcare costs than control participants at baseline. 3DFD participants had greater improvement in glycaemic control compared with control participants [â14 mmol/mol (â1.3%) vs. â6 mmol/mol (â0.6%) respectively, P < 0.001], adjusted for confounding. Total followâup healthcare costs remained higher in the 3DFD group compared with the control group (mean difference ÂŁ1715, 95% confidence intervals 591 to 2811), adjusted for confounding. The incremental costâeffectiveness ratio was ÂŁ398 per mmol/mol unit decrease in HbA1c, indicating the 3DFD intervention was more effective and costed more than usual care.
Conclusions
A biomedical, psychological and social criteriaâbased referral system for identifying and managing highâcost and highârisk individuals with poor glycaemic control can lead to improved health in all three dimensions
Herb network construction and co-module analysis for uncovering the combination rule of traditional Chinese herbal formulae
- Author
- Publication venue
- BioMed Central
- Publication date
- 01/01/2011
- Field of study
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
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- Warburton
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- Wester
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- Wicklund
- Wicklund
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- Williams
- Wilson
- Wilson
- Winer
- Wittich
- Wolbers
- Wolfe
- Wright
- Wu
- Wu
- X.
- Y.
- Y.
- Y.
- Y.
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- Y.
- Y.
- Y.
- Y.C.
- Y.C.
- Y.D.
- Y.J.
- Y.K.
- Y.S.
- Yamamoto
- Yamato
- Yang
- Yang
- Yang
- Yao
- Yeh
- Yi
- Yoh
- Yorita
- Yoshida
- Yu
- Yu
- Yu
- Yun
- Z.
- Zanetti
- Zeng
- Zhou
- Zucchelli
- Publication venue
- 'American Physical Society (APS)'
- Publication date
- 01/01/2012
- Field of study
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at â s = 8 TeV with the ATLAS detector
- Author
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fbâ1 of â s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at sâ=8 TeV with the ATLAS detector
- Author
- Aad G
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- Abdallah J
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- Yilmaz M
- Yoosoofmiya R
- Yorita K
- Yoshida R
- Yoshihara K
- Young C
- Young CJS
- Youssef S
- Yu DR
- Yu J
- Yu J
- Yu JM
- Yuan L
- Yurkewicz A
- Yusuff I
- Zabinski B
- Zaidan R
- Zaitsev AM
- Zaman A
- Zambito S
- Zanello L
- Zanzi D
- Zeitnitz C
- Zeman M
- Zemla A
- Zengel K
- Zenin O
- Zenis T
- Zerwas D
- Zhang D
- Zhang F
- Zhang H
- Zhang J
- Zhang L
- Zhang X
- Zhang Z
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou L
- Zhou N
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhukov K
- Zibell A
- Zieminska D
- Zimine NI
- Zimmermann C
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Zinonos Z
- Ziolkowski M
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zurzolo G
- Zutshi V
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2014
- Field of study
The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fbâ1 of protonâproton collision data at âs = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via tËâtÏË01 or tËâ bÏ˱1 âbW(â)ÏË01 , where ÏË01 (Ï˱1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of tË â tÏË01 . For a branching fraction of 100%, top squark masses in the range 270â645 GeV are excluded for ÏË01 masses below 30 GeV. For a branching fraction of 50% to either tË â tÏË01 or tË â bÏ˱1 , and assuming the Ï˱1 mass to be twice the ÏË01 mass, top squark masses in the range 250â550 GeV are excluded for ÏË01 masses below 60 GeV
Performance of the CMS Cathode Strip Chambers with Cosmic Rays
- Author
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- Publication venue
- 'IOP Publishing'
- Publication date
- 01/01/2009
- Field of study
The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device
in the CMS endcaps. Their performance has been evaluated using data taken
during a cosmic ray run in fall 2008. Measured noise levels are low, with the
number of noisy channels well below 1%. Coordinate resolution was measured for
all types of chambers, and fall in the range 47 microns to 243 microns. The
efficiencies for local charged track triggers, for hit and for segments
reconstruction were measured, and are above 99%. The timing resolution per
layer is approximately 5 ns
Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at âs=8TeV
- Author
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- Winklmeier F
- Winter BT
- Wittgen M
- Wittig T
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- Wollstadt SJ
- Wolter MW
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- Wosiek BK
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- Wu Y
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- Wyatt TR
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- Xella S
- Xiao M
- Xu D
- Xu L
- Yabsley B
- Yacoob S
- Yakabe R
- Yamada M
- Yamaguchi H
- Yamaguchi Y
- Yamamoto A
- Yamamoto K
- Yamamoto S
- Yamamura T
- Yamanaka T
- Yamauchi K
- Yamazaki Y
- Yan Z
- Yang H
- Yang H
- Yang UK
- Yang Y
- Yanush S
- Yao L
- Yao W-M
- Yasu Y
- Yatsenko E
- Ye J
- Ye S
- Yeletskikh I
- Yen AL
- Yildirim E
- Yildiz HD
- Yilmaz M
- Yoosoofmiya R
- Yorita K
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- Yoshihara K
- Young C
- Young CJS
- Youssef S
- Yu DR
- Yu J
- Yu J
- Yu JM
- Yuan L
- Yurkewicz A
- Yusuff I
- Zabinski B
- Zaidan R
- Zaitsev AM
- Zaman A
- Zambito S
- Zanello L
- Zanzi D
- Zeitnitz C
- Zeman M
- Zemla A
- Zengel K
- Zenin O
- Zenis T
- Zerwas D
- Zhang D
- Zhang F
- Zhang H
- Zhang J
- Zhang L
- Zhang X
- Zhang Z
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou L
- Zhou N
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhukov K
- Zibell A
- Zieminska D
- Zimine NI
- Zimmermann C
- Zimmermann R
- Zimmermann S
- Zimmermann S
- Zinonos Z
- Ziolkowski M
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zurzolo G
- Zutshi V
- Zwalinski L
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2014
- Field of study
The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fbâ1of data collected in protonâproton collisions at âs=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV
To hit or not to hit, that is the question -genome-wide structure-based druggability predictions for <i>pseudomonas aeruginosa </i>proteins
- Author
- A Gaulton
- A Krasowski
- A Oliver
- A Tripathi
- A Volkamer
- A Volkamer
- AC Cheng
- AL Hopkins
- ATR Laurie
- Aurijit Sarkar
- B Huang
- B Lee
- B Nisius
- B Shanmugham
- BI Schweitzer
- BLM De Jonge
- CY Wang
- D Brown
- DJ Payne
- E Perola
- EB Fauman
- F AgĂŒero
- GP Brady
- GR Bickerton
- J An
- J Desaphy
- J Liang
- J Seco
- J Zhang
- KA Sharp
- KP Peters
- L Moynie
- M Brylinski
- M Nayal
- M Weisel
- MA Jacobs
- MA Larkin
- MN Patel
- MS Alphey
- N Huang
- NT Liberati
- P Schmidtke
- PJ Hajduk
- R Uddin
- RA Laskowski
- Rafael J. Najmanovich
- RP Sheridan
- Ruth Brenk
- S Henrich
- SF Altschul
- SL McGovern
- T Schmidt
- TA Halgren
- V Le Guilloux
- W Blankenfeldt
- Publication venue
- 'Public Library of Science (PLoS)'
- Publication date
- 01/01/2015
- Field of study
Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large-scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa
Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir
- Author
- A Bruning
- A Onufriev
- A Onufriev
- A Petrelli
- AK Gupta
- AL Hopkins
- AL Hopkins
- AL Hopkins
- AM Aronov
- AN Jain
- B Apsel
- B Brooks
- B Jayaram
- CY Yang
- D Bashford
- D Gilbert
- D Sitkoff
- DA Case
- DA Case
- DC Rees
- DL Mobley
- DL Mobley
- G Badis
- G Manning
- G Rastelli
- GJ Martyna
- GR Zimmermann
- H Kitano
- H Kitano
- H Lu
- I Baris
- I Stich
- J Gills
- J Jia
- J Mestres
- J Roy
- J Srinivasan
- J Weiser
- J-PCG Ryckaert
- JA Blair
- JB Fitzgerald
- JC Phillips
- JD Carpten
- JD Durrant
- JP Plastaras
- JW Ponder
- K Yang
- L Castagnoli
- L Xie
- L Xie
- L Xie
- L Xie
- Lei Xie
- Li Xie
- M Feig
- M Schaefer
- MA Branca
- MA Fabian
- MJ Keiser
- MJ Keiser
- MK Gilson
- MR Lee
- MS Lee
- MV Sundaram
- O Trott
- P Csermely
- PA Kollman
- Philip E. Bourne
- Q Chen
- Q Meng
- R Hu
- RA Copeland
- RL Chang
- RP Araujo
- RP Araujo
- Ruth Nussinov
- S Iadevaia
- S Maddika
- S Nelander
- S Rajagopal
- S Suthram
- S Whittaker
- SE Feller
- SL Kinnings
- T Darden
- T Walsh
- TE Balius
- Thomas Evangelidis
- V Agoston
- WA Chow
- WA Chow
- WB Bernstein
- WH Li
- WL Jorgensen
- X Ju
- XH Ma
- Y Wu
- Z Zsoldos
- ZA Knight
- Publication venue
- Public Library of Science
- Publication date
- 01/04/2011
- Field of study
Nelfinavir is a potent HIV-protease inhibitor with pleiotropic effects in cancer cells. Experimental studies connect its anti-cancer effects to the suppression of the Akt signaling pathway, but the actual molecular targets remain unknown. Using a structural proteome-wide off-target pipeline, which integrates molecular dynamics simulation and MM/GBSA free energy calculations with ligand binding site comparison and biological network analysis, we identified putative human off-targets of Nelfinavir and analyzed the impact on the associated biological processes. Our results suggest that Nelfinavir is able to inhibit multiple members of the protein kinase-like superfamily, which are involved in the regulation of cellular processes vital for carcinogenesis and metastasis. The computational predictions are supported by kinase activity assays and are consistent with existing experimental and clinical evidence. This finding provides a molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir and presents opportunities to optimize the drug as a targeted polypharmacology agent
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