Cytology for PD-L1 testing : A systematic review

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZenecaPeer reviewedPublisher PD

An endogenous inhibitor of angiogenesis downregulated by hypoxia in human aortic valve stenosis promotes disease pathogenesis

Acknowledgements The authors would like to acknowledge the NHS Grampian Biorepository for their support and assistance with all immunohistochemistry. Sources of funding This work was generously funded by the British Heart Foundation, UK (FS/17/28/32807) and Grampian NHS Endowments.Peer reviewedPublisher PD

Five New Millisecond Pulsars From a Radio Survey of 14 Unidentified Fermi-LAT Gamma-ray Sources

We have discovered five millisecond pulsars (MSPs) in a survey of 14 unidentified Fermi-LAT sources in the southern sky using the Parkes radio telescope. PSRs J0101-6422, J1514-4946, and J1902-5105 reside in binaries, while PSRs J1658-5324 and J1747-4036 are isolated. Using an ephemeris derived from timing observations of PSR J0101-6422 (P =2.57 ms, DM=12 pc cm-3), we have detected {\gamma}-ray pulsations and measured its proper motion. Its {\gamma}-ray spectrum (a power law of {\Gamma} = 0.9 with a cutoff at 1.6 GeV) and efficiency are typical of other MSPs, but its radio and {\gamma}-ray light curves challenge simple geometric models of emission. The high success rate of this survey-enabled by selecting {\gamma}-ray sources based on their detailed spectral characteristics-and other similarly successful searches indicate that a substantial fraction of the local population of MSPs may soon be known.Comment: 6 pages, 3 figures, 2 tables, accepted by ApJ

Radio Detection of the Fermi LAT Blind Search Millisecond Pulsar J1311-3430

We report the detection of radio emission from PSR J1311-3430, the first millisecond pulsar discovered in a blind search of Fermi Large Area Telescope (LAT) gamma-ray data. We detected radio pulsations at 2 GHz, visible for <10% of ~4.5-hrs of observations using the Green Bank Telescope (GBT). Observations at 5 GHz with the GBT and at several lower frequencies with Parkes, Nancay, and the Giant Metrewave Radio Telescope resulted in non-detections. We also report the faint detection of a steep spectrum continuum radio source (0.1 mJy at 5 GHz) in interferometric imaging observations with the Jansky Very Large Array. These detections demonstrate that PSR J1311-3430, is not radio quiet and provides additional evidence that the radio beaming fraction of millisecond pulsars is very large. The radio detection yields a distance estimate of 1.4 kpc for the system, yielding a gamma-ray efficiency of 30%, typical of LAT-detected MSPs. We see apparent excess delay in the radio pulsar as the pulsar appears from eclipse and we speculate on possible mechanisms for the non-detections of the pulse at other orbital phases and observing frequencies.Comment: 6 pages, 4 figures. ApJ Letters, in pres

Timing analysis for 20 millisecond pulsars in the Parkes Pulsar Timing Array

We present timing models for 20 millisecond pulsars in the Parkes Pulsar Timing Array. The precision of the parameter measurements in these models has been improved over earlier results by using longer data sets and modelling the non-stationary noise. We describe a new noise modelling procedure and demonstrate its effectiveness using simulated data. Our methodology includes the addition of annual dispersion measure (DM) variations to the timing models of some pulsars. We present the first significant parallax measurements for PSRs J1024-0719, J1045-4509, J1600-3053, J1603-7202, and J1730-2304, as well as the first significant measurements of some post-Keplerian orbital parameters in six binary pulsars, caused by kinematic effects. Improved Shapiro delay measurements have resulted in much improved pulsar mass measurements, particularly for PSRs J0437-4715 and J1909-3744 with $M_p=1.44\pm0.07$ $M_\odot$ and $M_p=1.47\pm0.03$ $M_\odot$ respectively. The improved orbital period-derivative measurement for PSR J0437-4715 results in a derived distance measurement at the 0.16% level of precision, $D=156.79\pm0.25$ pc, one of the most fractionally precise distance measurements of any star to date.Comment: 21 pages, 5 figures, 7 tables. Accepted for publication in MNRA

PSR J2030+3641: radio discovery and gamma-ray study of a middle-aged pulsar in the now identified Fermi-LAT source 1FGL J2030.0+3641

In a radio search with the Green Bank Telescope of three unidentified low Galactic latitude Fermi-LAT sources, we have discovered the middle-aged pulsar J2030+3641, associated with 1FGL J2030.0+3641 (2FGL J2030.0+3640). Following the detection of gamma-ray pulsations using a radio ephemeris, we have obtained a phase-coherent timing solution based on gamma-ray and radio pulse arrival times that spans the entire Fermi mission. With a rotation period of 0.2 s, spin-down luminosity of 3e34 erg/s, and characteristic age of 0.5 Myr, PSR J2030+3641 is a middle-aged neutron star with spin parameters similar to those of the exceedingly gamma-ray-bright and radio-undetected Geminga. Its gamma-ray flux is 1% that of Geminga, primarily because of its much larger distance, as suggested by the large integrated column density of free electrons, DM=246 pc/cc. We fit the gamma-ray light curve, along with limited radio polarimetric constraints, to four geometrical models of magnetospheric emission, and while none of the fits have high significance some are encouraging and suggest that further refinements of these models may be worthwhile. We argue that not many more non-millisecond radio pulsars may be detected along the Galactic plane that are responsible for LAT sources, but that modified methods to search for gamma-ray pulsations should be productive -- PSR J2030+3641 would have been found blindly in gamma rays if only >0.8 GeV photons had been considered, owing to its relatively flat spectrum and location in a region of high soft background.Comment: Accepted for publication in ApJ, 9 pages, 6 figure

Characterization of the Myocardial Inflammatory Response in Acute Stress-Induced (Takotsubo) Cardiomyopathy

This work was supported by grants from NHS Grampian Endowments and British Heart Foundation Project Grant no. PG/15/108/31928 The authors have reported that they have no relationships relevant to the contents of this paper to disclose.Peer reviewedPublisher PD

Molecular testing in stage I–III non-small cell lung cancer : approaches and challenges

Precision medicine in non-small cell lung cancer (NSCLC) is a rapidly evolving area, with the development of targeted therapies for advanced disease and concomitant molecular testing to inform clinical decision-making. In contrast, routine molecular testing in stage I–III disease has not been required, where standard of care comprises surgery with or without adjuvant or neoadjuvant chemotherapy, or concurrent chemoradiotherapy for unresectable stage III disease, without the integration of targeted therapy. However, the phase 3 ADAURA trial has recently shown that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, reduces the risk of disease recurrence by 80% versus placebo in the adjuvant setting for patients with stage IB–IIIA EGFR mutation-positive NSCLC following complete tumor resection with or without adjuvant chemotherapy, according to physician and patient choice. Treatment with adjuvant osimertinib requires selection of patients based on the presence of an EGFR-TKI sensitizing mutation. Other targeted agents are currently being evaluated in the adjuvant and neoadjuvant settings. Approval of at least some of these other agents is highly likely in the coming years, bringing with it in parallel, a requirement for comprehensive molecular testing for stage I–III disease. In this review, we consider the implications of integrating molecular testing into practice when managing patients with stage I–III non-squamous NSCLC. We discuss best practices, approaches and challenges from pathology, surgical and oncology perspectives

Three Millisecond Pulsars in FERMI LAT Unassociated Bright Sources

We searched for radio pulsars in 25 of the non-variable, unassociated sources in the Fermi LAT Bright Source List with the Green Bank Telescope at 820 MHz. We report the discovery of three radio and gamma-ray millisecond pulsars (MSPs) from a high Galactic latitude subset of these sources. All of the pulsars are in binary systems, which would have made them virtually impossible to detect in blind gamma-ray pulsation searches. They seem to be relatively normal, nearby (<=2 kpc) millisecond pulsars. These observations, in combination with the Fermi detection of gamma-rays from other known radio MSPs, imply that most, if not all, radio MSPs are efficient gamma-ray producers. The gamma-ray spectra of the pulsars are power-law in nature with exponential cutoffs at a few GeV, as has been found with most other pulsars. The MSPs have all been detected as X-ray point sources. Their soft X-ray luminosities of ~10^{30-31} erg/s are typical of the rare radio MSPs seen in X-rays.Comment: Accepted for publication in ApJ Letter