The breast cancer screening programmes in the United Kingdom currently invite women aged 50-70 years for screening mammography every 3 years. Since the time the screening programmes were established, ...there has been debate, at times sharply polarised, over the magnitude of their benefit and harm, and the balance between them. The expected major benefit is reduction in mortality from breast cancer. The major harm is overdiagnosis and its consequences; overdiagnosis refers to the detection of cancers on screening, which would not have become clinically apparent in the woman's lifetime in the absence of screening. Professor Sir Mike Richards, National Cancer Director, England, and Dr Harpal Kumar, Chief Executive Officer of Cancer Research UK, asked Professor Sir Michael Marmot to convene and chair an independent panel to review the evidence on benefits and harms of breast screening in the context of the UK breast screening programmes. The panel, authors of this report, reviewed the extensive literature and heard testimony from experts in the field who were the main contributors to the debate. 85 references
ABSTRACT
We present the results of processing an additional 44 per cent of the High Time Resolution Universe South Low Latitude (HTRU-S LowLat) pulsar survey, the most sensitive blind pulsar survey ...of the southern Galactic plane to date. Our partially coherent segmented acceleration search pipeline is designed to enable the discovery of pulsars in short, highly accelerated orbits, while our 72-min integration lengths will allow us to discover pulsars at the lower end of the pulsar luminosity distribution. We report the discovery of 40 pulsars, including three millisecond pulsar-white dwarf binary systems (PSRs J1537−5312, J1547−5709, and J1618−4624), a black-widow binary system (PSR J1745−23) and a candidate black-widow binary system (PSR J1727−2951), a glitching pulsar (PSR J1706−4434), an eclipsing binary pulsar with a 1.5-yr orbital period (PSR J1653−45), and a pair of long spin-period binary pulsars which display either nulling or intermittent behaviour (PSRs J1812−15 and J1831−04). We show that the total population of 100 pulsars discovered in the HTRU-S LowLat survey to date represents both an older and lower luminosity population, and indicates that we have yet to reach the bottom of the luminosity distribution function. We present evaluations of the performance of our search technique and of the overall yield of the survey, considering the 94 per cent of the survey which we have processed to date. We show that our pulsar yield falls below earlier predictions by approximately 25 per cent (especially in the case of millisecond pulsars), and discuss explanations for this discrepancy as well as future adaptations in RFI mitigation and searching techniques which may address these shortfalls.
Abstract
We report the discovery of PSR J1757−1854, a 21.5-ms pulsar in a highly-eccentric, 4.4-h orbit with a neutron star (NS) companion. PSR J1757−1854 exhibits some of the most extreme ...relativistic parameters of any known pulsar, including the strongest relativistic effects due to gravitational-wave damping, with a merger time of 76 Myr. Following a 1.6-yr timing campaign, we have measured five post-Keplerian parameters, yielding the two component masses (mp = 1.3384(9) M⊙ and mc = 1.3946(9) M⊙) plus three tests of general relativity, which the theory passes. The larger mass of the NS companion provides important clues regarding the binary formation of PSR J1757−1854. With simulations suggesting 3-σ measurements of both the contribution of Lense–Thirring precession to the rate of change of the semimajor axis and the relativistic deformation of the orbit within ∼7–9 yr, PSR J1757−1854 stands out as a unique laboratory for new tests of gravitational theories.
Abstract Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing ...severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (⩾65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (⩾20%) or intermediate (10–20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10–20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem.
Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought ...to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes.
Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses.
Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS hazard ratio (HR) = 0.40, P < 0.001 in favour of pCR, DMFS (HR = 0.32, P < 0.001) and OS (HR = 0.32, P < 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1).
pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis.
EORTC 10994/BIG 1-00 Trial registration number NCT00017095.
Abstract
We report the joint WASP/KELT discovery of WASP-167b/KELT-13b, a transiting hot Jupiter with a 2.02-d orbit around a V = 10.5, F1V star with Fe/H = 0.1 ± 0.1. The 1.5 R
Jup planet was ...confirmed by Doppler tomography of the stellar line profiles during transit. We place a limit of <8 M
Jup on its mass. The planet is in a retrograde orbit with a sky-projected spin–orbit angle of λ = −165° ± 5°. This is in agreement with the known tendency for orbits around hotter stars to be more likely to be misaligned. WASP-167/KELT-13 is one of the few systems where the stellar rotation period is less than the planetary orbital period. We find evidence of non-radial stellar pulsations in the host star, making it a δ-Scuti or γ-Dor variable. The similarity to WASP-33, a previously known hot-Jupiter host with pulsations, adds to the suggestion that close-in planets might be able to excite stellar pulsations.
ABSTRACT
We report observed and derived timing parameters for three millisecond pulsars (MSPs) from observations collected with the Parkes 64-m telescope, Murriyang. The pulsars were found during ...reprocessing of archival survey data by Mickaliger et al. One of the new pulsars (PSR J1546–5925) has a spin period P = 7.8 ms and is isolated. The other two (PSR J0921–5202 with P = 9.7 ms and PSR J1146–6610 with P = 3.7 ms) are in binary systems around low-mass (${\gt}0.2\, {\rm M}_{\odot }$) companions. Their respective orbital periods are 38.2 and 62.8 d. While PSR J0921–5202 has a low orbital eccentricity e = 1.3 × 10−5, in keeping with many other Galactic MSPs, PSR J1146–6610 has a significantly larger eccentricity, e = 7.4 × 10−3. This makes it a likely member of a group of eccentric MSP–helium white dwarf binary systems in the Galactic disc whose formation is poorly understood. Two of the pulsars are co-located with previously unidentified point sources discovered with the Fermi satellite’s Large Area Telescope, but no γ-ray pulsations have been detected, likely due to their low spin-down powers. We also show that, particularly in terms of orbital diversity, the current sample of MSPs is far from complete and is subject to a number of selection biases.
We have analysed time-slice simulations from 17 global models, participating in the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), to explore changes in present-day (2000) ...hydroxyl radical (OH) concentration and methane (CH4) lifetime relative to preindustrial times (1850) and to 1980. A comparison of modeled and observation-derived methane and methyl chloroform lifetimes suggests that the present-day global multi-model mean OH concentration is overestimated by 5 to 10% but is within the range of uncertainties. The models consistently simulate higher OH concentrations in the Northern Hemisphere (NH) compared with the Southern Hemisphere (SH) for the present-day (2000; inter-hemispheric ratios of 1.13 to 1.42), in contrast to observation-based approaches which generally indicate higher OH in the SH although uncertainties are large. Evaluation of simulated carbon monoxide (CO) concentrations, the primary sink for OH, against ground-based and satellite observations suggests low biases in the NH that may contribute to the high north–south OH asymmetry in the models. The models vary widely in their regional distribution of present-day OH concentrations (up to 34%). Despite large regional changes, the multi-model global mean (mass-weighted) OH concentration changes little over the past 150 yr, due to concurrent increases in factors that enhance OH (humidity, tropospheric ozone, nitrogen oxide (NOx) emissions, and UV radiation due to decreases in stratospheric ozone), compensated by increases in OH sinks (methane abundance, carbon monoxide and non-methane volatile organic carbon (NMVOC) emissions). The large inter-model diversity in the sign and magnitude of preindustrial to present-day OH changes (ranging from a decrease of 12.7% to an increase of 14.6%) indicate that uncertainty remains in our understanding of the long-term trends in OH and methane lifetime. We show that this diversity is largely explained by the different ratio of the change in global mean tropospheric CO and NOx burdens (Delta CO/Delta NOx, approximately represents changes in OH sinks versus changes in OH sources) in the models, pointing to a need for better constraints on natural precursor emissions and on the chemical mechanisms in the current generation of chemistry-climate models. For the 1980 to 2000 period, we find that climate warming and a slight increase in mean OH (3.5 +/- 2.2%) leads to a 4.3 +/- 1.9% decrease in the methane lifetime. Analysing sensitivity simulations performed by 10 models, we find that preindustrial to present-day climate change decreased the methane lifetime by about four months, representing a negative feedback on the climate system. Further, we analysed attribution experiments performed by a subset of models relative to 2000 conditions with only one precursor at a time set to 1860 levels. We find that global mean OH increased by 46.4 +/- 12.2% in response to preindustrial to present-day anthropogenic NOx emission increases, and decreased by 17.3 +/-2.3%, 7.6 +/- 1.5%, and 3.1 +/- 3.0% due to methane burden, and anthropogenic CO, and NMVOC emissions increases, respectively.
ABSTRACT
The main goal of pulsar timing array experiments is to detect correlated signals such as nanohertz-frequency gravitational waves. Pulsar timing data collected in dense monitoring campaigns ...can also be used to study the stars themselves, their binary companions, and the intervening ionized interstellar medium. Timing observations are extraordinarily sensitive to changes in path-length between the pulsar and the Earth, enabling precise measurements of the pulsar positions, distances and velocities, and the shapes of their orbits. Here we present a timing analysis of 25 pulsars observed as part of the Parkes Pulsar Timing Array (PPTA) project over time spans of up to 24 yr. The data are from the second data release of the PPTA, which we have extended by including legacy data. We make the first detection of Shapiro delay in four Southern pulsars (PSRs J1017−7156, J1125−6014, J1545−4550, and J1732−5049), and of parallax in six pulsars. The prominent Shapiro delay of PSR J1125−6014 implies a neutron star mass of Mp = 1.5 ± 0.2 M⊙ (68 per cent credibility interval). Measurements of both Shapiro delay and relativistic periastron advance in PSR J1600−3053 yield a large but uncertain pulsar mass of $M_p = 2.06^{+0.44}_{-0.41}$ M⊙ (68 per cent credibility interval). We measure the distance to PSR J1909−3744 to a precision of 10 lyr, indicating that for gravitational wave periods over a decade, the pulsar provides a coherent baseline for pulsar timing array experiments.
Since the start of the Wide-angle Search for Planets (WASP) program, more than 160 transiting exoplanets have been discovered in the WASP data. In the past, possible transit-like events identified by ...the WASP pipeline have been vetted by human inspection to eliminate false alarms and obvious false positives. The goal of this paper is to assess the effectiveness of machine learning as a fast, automated, and reliable means of performing the same functions on ground-based wide-field transit-survey data without human intervention. To this end, we have created training and test data sets made up of stellar light curves showing a variety of signal types including planetary transits, eclipsing binaries, variable stars, and non-periodic signals. We use a combination of machine-learning methods including Random Forest Classifiers (RFCs) and convolutional neural networks (CNNs) to distinguish between the different types of signals. The final algorithms correctly identify planets in the test data ∼90 per cent of the time, although each method on its own has a significant fraction of false positives. We find that in practice, a combination of different methods offers the best approach to identifying the most promising exoplanet transit candidates in data from WASP, and by extension similar transit surveys.
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