79 research outputs found
A new measurement of direct CP violation in two pion decays of the neutral kaon
The NA48 experiment at CERN has performed a new measurement of direct CP
violation, based on data taken in 1997 by simultaneously collecting K_L and K_S
decays into pi0pi0 and pi+pi-. The result for the CP violating parameter
Re(epsilon'/epsilon) is (18.5 +/- 4.5(stat)} +/- 5.8 (syst))x10^{-4}.Comment: 18 pages, 6 figure
Association of interatrial septal abnormalities with cardiac impulse conduction disorders in adult patients: experience from a tertiary center in Kosovo
Interatrial septal disorders, which include: atrial septal defect, patent foramen ovale and atrial septal aneurysm, are frequent congenital anomalies found in adult patients. Early detection of these anomalies is important to prevent their hemodynamic and/or thromboembolic consequences. The aims of this study were: to assess the association between impulse conduction disorders and anomalies of interatrial septum; to determine the prevalence of different types of interatrial septum abnormalities; to assess anatomic, hemodynamic, and clinical consequences of interatrial septal pathologies. Fifty-three adult patients with impulse conduction disorders and patients without ECG changes but with signs of interatrial septal abnormalities, who were referred to our center for echocardiography, were included in a prospective transesophageal echocardiography study. Interatrial septal anomalies were detected in around 85% of the examined patients. Patent foramen ovale was encountered in 32% of the patients, and in combination with atrial septal aneurysm in an additional 11.3% of cases. Atrial septal aneurysm and atrial septal defect were diagnosed with equal frequency in 20.7% of our study population. Impulse conduction disorders were significantly more suggestive of interatrial septal anomalies than clinical signs and symptoms observed in our patients (84.91% vs 30.19%, P=0.002). Right bundle branch block was the most frequent impulse conduction disorder, found in 41 (77.36%) cases. We conclude that interatrial septal anomalies are highly associated with impulse conduction disorders, particularly with right bundle branch block. Impulse conduction disorders are more indicative of interatrial septal abnormalities in earlier stages than can be understood from the patientâs clinical condition
A precision measurement of direct CP violation in the decay of neutral kaons into two pions
The direct CP violation parameter Re(epsilon'/epsilon) has been measured from
the decay rates of neutral kaons into two pions using the NA48 detector at the
CERN SPS. The 2001 running period was devoted to collecting additional data
under varied conditions compared to earlier years (1997-99). The new data yield
the result: Re(epsilon'/epsilon) = (13.7 +/- 3.1) times 10^{-4}. Combining this
result with that published from the 1997, 98 and 99 data, an overall value of
Re(epsilon'/epsilon) = (14.7 +/- 2.2) times 10^{-4} is obtained from the NA48
experiment.Comment: 19 pages, 5 figures, to be published in Physics Letters
Organizational and Leadership Implications for Transformational Development
Transformational development is a concept of change that originated in the Christian context but has now become generally used in the work of both secular and faith-based organizations. The growing use of the concept by organizations that are fundamentally different has naturally led to some confusion about what the concept means and what it takes to effectively implement it. In this article, we describe the key features of the concept and how they are important in determining the organizational requirements for its effective implementation. Drawing on a few cases, the paper highlights the centrality of faith in transformational development work
Variation with mass of B(E3;01+â31-) transition rates in A=124-134 even-mass xenon nuclei
B(E3;01+â31-) transition matrix elements have been measured for even-mass Xe124-134 nuclei using subbarrier Coulomb excitation in inverse kinematics. The trends in energy E(3-) and B(E3;01+â31-) excitation strengths are well reproduced using phenomenological models based on a strong coupling picture with a soft quadrupole mode and an increasing occupation of the intruder h11/2 orbital
The path to a better biomarker: Application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice
Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying 651% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin\u2013stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. \ua9 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting
Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study
Background
The association of fitness with cancer risk is not clear.
Methods
We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (Nâ=â72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.
Results
After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5âml O2â
minâ1â
kgâ1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HRâ=â0.81, 95% CI: 0.73â0.89), colorectal (0.94, 0.90â0.99), and breast cancer (0.96, 0.92â0.99). In MR analyses, a 0.5âSD increase in genetically predicted O2â
minâ1â
kgâ1 fat-free mass was associated with a lower risk of breast cancer (ORâ=â0.92, 95% CI: 0.86â0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated.
Discussion
Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention
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