Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Imaging spectroscopy of solar microwave radiation. I. Flaring emission

We present observations of an impulsive microwave burst on the Sun with both high spatial and spectral resolution, made with the Solar Array at the Owens Valley Radio Observatory. The burst was imaged in total intensity, as well as both right and left circular polarization, at 24 frequencies distributed logarithmically over the range 2.4-14.0 GHz, with spatial resolution ranging from ∼5″-29″. This powerful new technique for studying microwave bursts shows that: (1) even a relatively weak burst with a simple temporal and spectral morphology in total power can have a complex spatial structure, comprising three distinct sources; (2) the burst structure changes with frequency so that images at widely spaced frequencies show a different number and/or location of sources, whereas images at closely spaced frequencies reveal the relationship between sources at different frequencies; and (3) the brightness temperature spectrum of each source is different, so that the composite total-power spectrum is not representative of the spectrum of any individual source. We used the measured brightness temperature spectrum to infer the emission process responsible for each microwave source, and to derive physical conditions in the source region. We confirmed our predictions using soft X-ray measurements from GOES, soft X-ray images from Yohkoh, and Ha flare images together with sunspot and magnetogram images from the Big Bear Solar Observatory. The primary microwave source, located close to but not coincident with either the lone flaring soft X-ray kernel or primary Ha kernel, had a peak brightness temperature of only ∼ 10 7 K, but nevertheless was produced by nonthermal gyrosynchrotron emission. The two secondary sources, both without any soft X-ray or Hα counterparts, had lower turnover frequencies but also were produced by nonthermal gyrosynchrotron emission. These sources were connected to the primary flare site by magnetic loops visible in soft X-rays, suggesting that their nonthermal electrons escaped from the primary microwave source.link_to_subscribed_fulltex

The STIX Imaging Concept

We provide a mathematical description of the imaging concept of the Spectrometer/Telescope for Imaging X-rays (STIX) onboard Solar Orbiter. Specifically, we describe the STIX indirect-imaging technique, which is based on spatial modulation of the X-ray photon flux by means of tungsten grids, and we show that each of 30 STIX imaging sub-collimators measures a Fourier component of the flaring X-ray source corresponding to a specific two-dimensional angular frequency. We also provide details about the count-distribution model, which describes the relationship between the photon flux and the measured pixel counts. The derived imaging model is the fundamental starting point both for the interpretation of STIX data and for the description of the data-calibration process. Finally, we provide an overview of the algorithms implemented for the solution of the imaging problem and a comparison of the results obtained with these different methods in the case of the SOL2022-03-31T18 flaring event

The E2F family: specific functions and overlapping interests

The E2F transcription factors are key regulators of cell cycle progression and the E2F field has made rapid advances since its advent in 1986. Yet, while our understanding of the roles and functions of the E2F family has made enormous progress, with each discovery new questions arise. In this review, we summarise the most recent advances in the field and discuss the remaining key questions. In particular, we will focus on how specificity is achieved among the E2Fs