Doppler images of II Pegasi for 2004-2010

Aims. We study the spot activity of II Peg during the years 2004-2010 to determine long- and short-term changes in the magnetic activity. In a previous study, we detected a persistent active longitude, as well as major changes in the spot configuration occurring on a timescale of shorter than a year. The main objective of this study is to determine whether the same phenomena persist in the star during these six years of spectroscopic monitoring. Methods. The observations were collected with the high-resolution SOFIN spectrograph at the Nordic Optical Telescope. The temperature maps were calculated using a Doppler imaging code based on Tikhonov regularization. Results. We present 12 new temperature maps that show spots distributed mainly over high and intermediate latitudes. In each image, 1-3 main active regions can be identified. The activity level of the star is clearly lower than during our previous study for the years 1994-2002. In contrast to the previous observations, we detect no clear drift of the active regions with respect to the rotation of the star. Conclusions. Having shown a systematic longitudinal drift of the spot-generating mechanism during 1994-2002, the star has clearly switched to a low-activity state for 2004-2010, during which the spot locations appear more random over phase space. It could be that the star is near to a minimum of its activity cycle.Comment: Accepted for publication in Astron. and Astrophys., 8 pages, 5 figure

The impact of COVID-19 on cancer care and oncology clinical research: an experts' perspective

The coronavirus disease-19 (COVID-19) pandemic promises to have lasting impacts on cancer clinical trials that could lead to faster patient access to new treatments. In this article, an international panel of oncology experts discusses the lasting impacts of the pandemic on oncology clinical trials and proposes solutions for clinical trial stakeholders, with the support of recent data on worldwide clinical trials collected by IQVIA. These lasting impacts and proposed solutions encompass three topic areas. Firstly, acceleration and implementation of new operational approaches to oncology trials with patient-centric, fully decentralized virtual approaches that include remote assessments via telemedicine and remote devices. Geographical differences in the uptake of remote technology, including telemedicine, are discussed in the article, focusing on the impact of the local adoption of new operational approaches. Secondly, innovative clinical trials. The pandemic has highlighted the need for new trial designs that accelerate research and limit risks and burden for patients while driving optimization of clinical trial objectives and endpoints, while testing is being minimized. Areas of considerations for clinical trial stakeholders are discussed in detail. In addition, the COVID-19 pandemic has exposed the underrepresentation of minority groups in clinical trials; the approach for oncology clinical trials to improve generalizability of efficacy and outcomes data is discussed. Thirdly, a new problem-focused collaborative framework between oncology trial stakeholders, including decision makers, to leverage and further accelerate the innovative approaches in clinical research developed during the COVID-19 pandemic. This could shorten timelines for patient access to new treatments by addressing the cultural and technological barriers to adopting new operational approaches and innovative clinical trials. The role of the different stakeholders is described, with the aim of making COVID-19 a catalyst for positive change in oncology clinical research and eventually in cancer care

On the Contribution of Unresolved Galactic Stars to the Diffuse Soft X-ray Background

Using stellar luminosity functions derived from ROSAT data, the contributions of Galactic stars to the diffuse X-ray background are calculated for ROSAT PSPC energy bands. The model follows that of Guillout et al. (1996), but uses ROSAT rather than {\it Einstein} data to determine the intrinsic luminosity distributions. The model adequately predicts the numbers of stellar sources observed in deep ROSAT surveys. The contribution of unresolved stellar sources to the ROSAT All-Sky Survey at the Galactic poles is 6.85, 4.76, and 4.91 $\times$ counts s$^{-1}$ arcmin$^{-2}$ in bands R12 (1/4 keV), R45(3/4 keV), and R67(1.5 keV), respectively, which is equivalent to 4.66, 31.3 and 26.9 $\times10^{-14}$ ergs cm$^{-2}$ s$^{-1}$ deg$^{-2}$.Comment: 14 pages, 8 figures, accepted by Ap

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

Epigenetic regulators, such as EZH2, are frequently mutated in cancer, and loss-of-function EZH2 mutations are common in myeloid malignancies. We have examined the importance of cellular context for Ezh2 loss during the evolution of acute myeloid leukemia (AML), where we observed stage-specific and diametrically opposite functions for Ezh2 at the early and late stages of disease. During disease maintenance, WT Ezh2 exerts an oncogenic function that may be therapeutically targeted. In contrast, Ezh2 acts as a tumor suppressor during AML induction. Transcriptional analysis explains this apparent paradox, demonstrating that loss of Ezh2 derepresses different expression programs during disease induction and maintenance. During disease induction, Ezh2 loss derepresses a subset of bivalent promoters that resolve toward gene activation, inducing a feto-oncogenic program that includes genes such as Plag1, whose overexpression phenocopies Ezh2 loss to accelerate AML induction in mouse models. Our data highlight the importance of cellular context and disease phase for the function of Ezh2 and its potential therapeutic implications.The Huntly laboratory is funded by CRUK (program C18680/ A25508), the European Research Council (grant 647685 COMAL), the Kay Kendall Leukaemia Fund, the Medical Research Council (MRC), Bloodwise, the Wellcome Trust, and the Cambridge National Institute of Health Research Biomedical Research Centre. F. Basheer is a recipient of a Wellcome Trust PhD for Clinicians award. P. Gallipoli is funded by the Wellcome Trust (109967/Z/15/Z). We acknowledge the Wellcome Trust/ MRC center grant (097922/Z/11/Z) and support from Wellcome Trust strategic award 100140. Research in the laboratory is also supported by core funding from the Wellcome Trust and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. This research was supported by the Cambridge National Institute of Health Research Biomedical Research Centre Cell Phenotyping Hub

Blinatumomab compared with standard of care for the treatment of adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia

Background A single‐arm, phase 2 trial demonstrated the efficacy and safety of blinatumomab, a bispecific T‐cell–engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with blinatumomab with those of a historical control treated with the standard of care (SOC). Methods The blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second‐generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 blinatumomab study in r/r Philadelphia chromosome–negative ALL. Results In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61‐3.89) or 1.70 (95% credible interval [CrI], 0.94‐2.94) with Bayesian data augmentation. Overall survival favored blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57‐1.14) or 0.77 (95% CrI, 0.61‐0.96) with Bayesian data augmentation. Conclusions These results further support blinatumomab as a treatment option for patients with r/r Ph+ ALL

The occurrence and management of fluid retention associated with TKI therapy in CML, with a focus on dasatinib

Tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib are indicated as second-line treatment for chronic myeloid leukemia resistant or intolerant to the current first-line TKI imatinib. These are agents are well tolerated, but potent and as such should be monitored for potentially serious side-effects like fluid retention and pleural effusions. Here we present key clinical trial data and safety considerations for all FDA approved TKIs in context for effective management of fluid retention and pleural effusions. Altering the dasatinib regimen from 70 mg twice daily to 100 mg daily reduces the risk of pleural effusion for patients taking dasatinib. Should pleural effusion develop, dasatinib should be interrupted until the condition resolves. Patients with a history of pleural effusion risk factors should be monitored closely while taking dasatinib. Patients receiving imatinib and nilotinib are not without risk of fluid retention. All patients should also be educated to recognize and report key symptoms of fluid retention or pleural effusion. Pleural effusions are generally managed by dose interruption/reduction and other supportive measures in patients with chronic myeloid leukemia receiving dasatinib therapy