Diagnosis of aspergillosis by PCR: clinical considerations and technical tips

Standardization of Aspergillus polymerase chain reaction (PCR) protocols has progressed, and analytical validity of blood-based assays has been formally established. It remains necessary to consider how the tests can be used in practice to maximize clinical utility. To determine the optimal diagnostic strategies and influence on patient management, several factors require consideration, including the patient population, incidence of invasive aspergillosis (and other fungal disease), and the local antifungal prescribing policy. Technical issues such as specimen type, ease of sampling, frequency of testing, access to testing centers, and time to reporting will also influence the use of PCR in clinical practice. Interpretation of all diagnostic tests is dependent on the clinical context and molecular assays are no exception, but with the proposal to incorporate Aspergillus PCR into the second revision of the consensus guidelines for defining invasive fungal disease the acceptance and understanding of molecular tests should improve

Perceived patient burden and acceptability of whole body MRI for staging lung and colorectal cancer; comparison with standard staging investigations

Objectives – To evaluate perceived patient burden and acceptability of whole body MRI (WB-MRI) compared to standard staging investigations, and identify predictors of reduced tolerance. Methods – Patients recruited to multi-centre trials comparing WB-MRI with standard staging scans for lung and colorectal cancer were invited to complete two questionnaires: a baseline questionnaire at recruitment, measuring demographics, comorbidities, and distress; and a follow-up questionnaire after staging, measuring recovery time, comparative acceptability/ satisfaction between WB-MRI and CT (colorectal cancer) and PET-CT (lung cancer), and perceived scan burden (scored 1 low to 7 high). Results – 115 patients (median age 66.3 years; 67 males) completed follow-up and 103 baseline questionnaires. Sixty-nine (63.9%) reported “immediate” recovery from WB-MRI and 73 (65.2%) judged it “very acceptable”. Perceived WB-MRI burden was greater than for CT (p<0.001) and PET-CT (p<0.001). High distress and co-morbidities were associated with greater WB-MRI burden in adjusted analyses, with deprivation only approaching significance (adjusted regression Beta=0.223, p=0.025; Beta=0.191, p=0.048; Beta = -0.186, p=0.059 respectively). Age (p=0.535), gender (p=0.389), ethnicity (p=0.081) and cancer type (p=0.201) were not predictive of WB-MRI burden. Conclusions: WB-MRI is marginally less acceptable and more burdensome than standard scans, particularly for patients with pre-existing distress and comorbidities. Advances in knowledge: This research shows that WB-MRI scan burden, although low, is higher than for current staging modalities among patients with suspected colorectal or lung cancer. Psychological and physical co-morbidities, adversely impact on patient experience of WB-MRI. Patients with high distress or comorbid illness may need additional support to undergo a WB-MRI

“Low FIT” Colorectal Cancer: A four-year comparison of the Nottingham “4F” protocol with FIT10 in symptomatic patients.

Aim:To evaluate colorectal cancer outcomes after “low” (sub-threshold) Faecal Immunochemical Test (FIT) results in symptomatic patients tested in primary care.Method:Retrospective audit of 35,289 patients with FIT results, having consulted their general practitioner with lower gastrointestinal symptoms, and subsequent colorectal cancer (CRC) diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local “4F” protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, Full blood count (FBC), Ferritin and Finger.Outcome: Detection rates of CRC, missed CRC and time to diagnosis in local “4F” protocols for patients with a sub-threshold faecal Haemoglobin (fHb) result compared to thresholds of 10 and 20µgHb/g Faeces.Results:A single threshold of 10 µgHb/g Faeces identifies a population in whom the risk of CRC is 0.2% but would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham “4F” protocol would have missed fewer CRCs (42 of 599 (7%)) despite using a threshold of 20 µgHb/g Faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays.Conclusion:Combination of FIT with blood results and DRE (“4F”) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb result spectrum

‘Low’ faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham ‘4F’ protocol with FIT10 in symptomatic patients

Aim: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after ‘low’ (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. Method: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local ‘4F’ protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 μg Hb/g faeces. Results: A single threshold of 10 μg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 μg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. Conclusion: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS

A measurement is presented of the $t\bar{t}$ inclusive production cross-section in $pp$ collisions at a center-of-mass energy of $\sqrt{s}=8$ TeV using data collected by the ATLAS detector at the CERN Large Hadron Collider. The measurement was performed in the lepton+jets final state using a data set corresponding to an integrated luminosity of 20.3 fb$^{-1}$. The cross-section was obtained using a likelihood discriminant fit and $b$-jet identification was used to improve the signal-to-background ratio. The inclusive $t\bar{t}$ production cross-section was measured to be $260\pm 1{\textrm{(stat.)}} ^{+22}_{-23} {\textrm{(syst.)}}\pm 8{\textrm{(lumi.)}}\pm 4{\mathrm{(beam)}}$ pb assuming a top-quark mass of 172.5 GeV, in good agreement with the theoretical prediction of $253^{+13}_{-15}$ pb. The $t\bar{t}\to (e,\mu)+{\mathrm{jets}}$ production cross-section in the fiducial region determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3 figures, 2 tables, all figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06

Measurement of the charge asymmetry in dileptonic Decays of top quark pairs in pp collisions at √ s = 7 TeV using the ATLAS detector

A measurement of the top-antitop (tt) charge asymmetry is presented using data corresponding to an integrated luminosity of 4.6 fb −1 of LHC pp collisions at a centre- of-mass energy of 7 TeV collected by the ATLAS detector. Events with two charged leptons, at least two jets and large missing transverse momentum are selected. Two observables are studied: A tt/C, based on the reconstructed tt final state. The asymmetries are measured to be A ll/C = 0.024 +/- 0.015 (stat.) +/- 0.009 (syst.) Att/C = 0.021 +/- 0.025 (stat.) +/- 0.017 (syst.) The measured values are in agreement with the Standard Model predictions