Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Cell surface antigens in renal tumour cells: detection by immunoluminescence and enzymatic analysis

Two renal cell carcinoma cell lines (49RC 43STR and 75RC 2STR) were characterized by detection of the cell surface proteins: CD44(var), intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator (uPA) and its receptor and aminopeptidase N (APN). To detect their localization the immunoluminescent technique was used. In addition, the enzyme activity of uPA and APN was investigated in cell suspensions as well as in monolayers. The latter procedure was more advantageous since the additional use of HPLC permits a single registration of the fluorescent hydrolysis-product AMC (7-amino-4-methylcoumarin) without interference by cellular autofluorescence or non-reacted fluorescent substrate. Unlike 75RC 2STR, the cell line 49RC 43STR expressed high levels of uPA and APN. Contrary to that the cell line 75RC 2STR expressed high levels of ICAM-1 and CD44(v6), whereas 49RC 43STR showed a low level of ICAM-1 and no distinct light signal with anti-CD44(v6). The uPA activity was measured directly as well as indirectly (via plasmin) with the substrate Z-Gly-Gly-Arg-AMC. Both activator and plasmin activity were inhibited by D-Val-Phe-Lys-CMK and phenylmethylsulfonyl fluoride. The anti-catalytic antibody to uPA and that to uPA receptor were found to be inhibiting the uPA activity in a concentration-dependent manner. APN activity was assayed using alanine-p-nitroanilide. Peptidase activity was effectively inhibited by 1,10-phenanthroline and partly inhibited by ethylenediamine-tetraacetic acid. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Cost of antipsychotic polypharmacy in the treatment of schizophrenia

<p>Abstract</p> <p>Background</p> <p>This study compared the costs of antipsychotic polypharmacy for patients who initiated on 1 of the 3 most commonly prescribed atypical antipsychotics – olanzapine, quetiapine, or risperidone.</p> <p>Methods</p> <p>Data were drawn from a large, prospective, naturalistic, multi-site, nonrandomized study of treatment for schizophrenia in the United States conducted between July 1997 and September 2003. Participants who were initiated on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276) were followed for 1 year post initiation and compared on: (a) average daily cost of the index antipsychotic while on the index antipsychotic, (b) average daily cost of the coprescribed antipsychotics while on the index antipsychotic, (c) average daily cost of the index antipsychotic and the coprescribed antipsychotics while on the index antipsychotic, (d) total annual cost of antipsychotic medications prescribed in the year following initiation on the index antipsychotic, using propensity score-adjusted bootstrap resampling method. Average daily antipsychotic costs and total annual antipsychotic costs were also estimated using more recent (2004) antipsychotic drug prices.</p> <p>Results</p> <p>During the 1 year following initiation on the index antipsychotic, the total average daily cost of the index antipsychotic was higher for quetiapine ($15.33) than olanzapine ($13.90, p < .05) and risperidone ($11.04, p < .01), although the average daily cost of the index antipsychotic was higher for olanzapine ($10.08) than risperidone ($6.74, p < .01) or quetiapine ($6.63, p < .01). Lower total average daily costs were observed in risperidone than olanzapine or quetiapine. Significantly lower average daily cost of concomitant antipsychotic medications for olanzapine ($3.82) compared to quetiapine ($8.70, p < .01) or risperidone-initiated patients ($4.30, p < .01) contributed to the lower average daily cost of all antipsychotic medication for olanzapine-initiated patients. Each dollar spent on the index antipsychotic was accompanied by spending an additional$1.31 on concomitant antipsychotics for quetiapine compared to $0.64 for risperidone and$0.38 for olanzapine-initiated patients. A separate intent-to-treat analysis of the total annual antipsychotic cost found a significantly higher total annual antipsychotic cost for quetiapine-initiated patients ($5320) compared to olanzapine ($4536, p < .01) or risperidone ($3813, p < .01).</p> <p>Conclusion</p> <p>Prevalent antipsychotic polypharmacy adds substantial cost to the treatment of schizophrenia. Comparison of medication costs need to address the costs of all antipsychotics. A better understanding of concomitant antipsychotic costs provides a more accurate portrayal of antipsychotic medication costs in the treatment of schizophrenia.</p

Recombination Phenotypes of Escherichia coli greA Mutants

<p>Abstract</p> <p>Background</p> <p>The elongation factor GreA binds to RNA polymerase and modulates transcriptional pausing. Some recent research suggests that the primary role of GreA may not be to regulate gene expression, but rather, to promote the progression of replication forks which collide with RNA polymerase, and which might otherwise collapse. Replication fork collapse is known to generate dsDNA breaks, which can be recombinogenic. It follows that GreA malfunction could have consequences affecting homologous recombination.</p> <p>Results</p> <p><it>Escherichia coli </it>mutants bearing substitutions of the active site acidic residues of the transcription elongation factor GreA, D41N and E44K, were isolated as suppressors of growth inhibition by a toxic variant of the bacteriophage lambda Red-beta recombination protein. These mutants, as well as a D41A <it>greA </it>mutant and a <it>greA </it>deletion, were tested for proficiency in recombination events. The mutations were found to increase the efficiency of RecA-RecBCD-mediated and RecA-Red-mediated recombination, which are replication-independent, and to decrease the efficiency of replication-dependent Red-mediated recombination.</p> <p>Conclusion</p> <p>These observations provide new evidence for a role of GreA in resolving conflicts between replication and transcription.</p

Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well

Ion traps with enhanced optical and physical access

Small, controllable, highly accessible quantum systems can serve as probes at the single quantum level to study multiple physical effects, for example in quantum optics or for electric and magnetic field sensing. The applicability of trapped atomic ions as probes is highly dependent on the measurement situation at hand and thus calls for specialized traps. Previous approaches for ion traps with enhanced optical access included traps consisting of a single ring electrode or two opposing endcap electrodes. Other possibilities are planar trap geometries, which have been investigated for Penning traps and rf-trap arrays. By not having the electrodes lie in a common plane the optical access in the latter cases can be substantially increased. Here, we discuss the fabrication and experimental characterization of a novel radio-frequency (rf) ion trap geometry. It has a relatively simple structure and provides largely unrestricted optical and physical access to the ion, of up to 96% of the total 4pi solid angle in one of the three traps tested. We also discuss potential applications in quantum optics and field sensing. As a force sensor, we estimate sensitivity to forces smaller than 1 yN Hz^(-1/2).Comment: 6 pages, 3 figures. Corrections of some typos, application section expanded to account for reviewer comment

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Careers of highly educated self-initiated expatriates : observations from studies among Finnish business professionals

This chapter reviews existing literature about the careers of self-initiated expatriates and analyzes the different studies carried out among university level educated Finnish business professionals. A series of studies carried out among members of the Finnish Association of Business School Graduates during the last 15 years was cross-analyzed. The studies are based on three surveys and further interviews among their expatriate members (1999, 2004 and a follow-up study in 2012) also involving SIEs. Therefore, this chapter provide an overview of what we know about the careers of Finnish SIEs and show evidence of (1) their career motives, (2) the role of family considerations in the career decision making of SIEs, (3) the development of career capital and social capital during SIE-experiences, and also (4) longer-term career impacts of SIE-experiences. Based on the literature review and analysis of above mentioned studies we highlight the gaps in in the knowledge about SIEs and suggest areas where further research is needed.fi=vertaisarvioitu|en=peerReviewed

Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

BACKGROUND: Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy) is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. METHODS: Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796) who were initiated during the study on olanzapine (N = 405), quetiapine (N = 115), or risperidone (N = 276). The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. RESULTS: During the 1-year period, only a third (35.7%) of the patients were treated predominately with monotherapy (>300 days). Most patients (57.7%) had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days). Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043) or quetiapine (p = .002). The number of monotherapy days was significantly greater for olanzapine than quetiapine (p < .001), but not for olanzapine versus risperidone, or for risperidone versus quetiapine-initiated patients. CONCLUSION: Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic polypharmacy for prolonged periods is very common during the treatment of schizophrenia patients in usual care settings. In addition, in this non-randomized naturalistic observational study, the most commonly used atypical antipsychotics significantly differed on the rate and duration of antipsychotic monotherapy. Reasons for and the impact of the predominant use of polypharmacy will require further study

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