Observational signatures of mass-loading in jets launched by rotating black holes

It is widely believed that relativistic jets in X-ray binaries (XRBs) and active-galactic nuclei are powered by the rotational energy of black holes. This idea is supported by general-relativistic magnetohydrodynamic (GRMHD) simulations of accreting black holes, which demonstrate efficient energy extraction via the Blandford–Znajek mechanism. However, due to uncertainties in the physics of mass loading, and the failure of GRMHD numerical schemes in the highly magnetized funnel region, the matter content of the jet remains poorly constrained. We investigate the observational signatures of mass loading in the funnel by performing general-relativistic radiative transfer calculations on a range of 3D GRMHD simulations of accreting black holes. We find significant observational differences between cases in which the funnel is empty and cases where the funnel is filled with plasma, particularly in the optical and X-ray bands. In the context of Sgr A*, current spectral data constrains the jet filling only if the black hole is rapidly rotating with a gsim 0.9. In this case, the limits on the infrared flux disfavor a strong contribution from material in the funnel. We comment on the implications of our models for interpreting future Event Horizon Telescope observations. We also scale our models to stellar-mass black holes, and discuss their applicability to the low-luminosity state in XRBs

High energy radiation from jets and accretion disks near rotating black holes

We model the low/hard state in X-ray binaries as a magnetically arrested accretion flow, and calculate the resulting radiation using a general-relativistic radiative transport code. Firstly, we investigate the origin of the high-energy emission. We find the following indications of a significant jet contribution at high energies: (i) a pronounced γ-ray peak at ∼ 1023 Hz, (ii) a break in the optical/UV band where the spectrum changes from disk to jet dominated, and (iii) a low-frequency synchrotron peak ≲ 1014 Hz implies that a significant fraction of any observed X-ray and γ-ray emission originates in the jet. Secondly, we investigate the effects of black hole spin on the high-energy emission. We find that the X-ray and γ-ray power depend strongly on spin and inclination angle. Surprisingly, this dependence is not a result of the Blandford-Znajek mechanism, but instead can be understood as a redshift effect. For rapidly rotating black holes, observers with large inclinations see deeper into the hot, dense, highly-magnetized inner regions of the accretion flow. Since the lower frequency emission originates at larger radii, it is not significantly affected by the spin. Therefore, the ratio of the X-ray to near-infrared power is an observational probe of black hole spin

Let’s talk about sex(ual) wellbeing! Staff perceptions of implementing a novel service for people with Multiple Sclerosis

BACKGROUND: In people with multiple sclerosis (PwMS), a complex interplay of neurological dysfunction, polypharmacy and psychological issues, contrive to impair their sexual and reproductive wellbeing. Realising an unmet need, the Tayside MS service in collaboration with a sexual health clinician (LJ), established a ‘Pelvic Health Clinic’ to improve quality of life for PwMS. OBJECTIVE: To explore clinician's perceptions of implementing an MS Pelvic Health service with a view to establishing future outcomes for health care professionals about the utility in such a service. METHOD: In this small-scale qualitative case study, we explored clinician's perceptions of such a clinic adjunct. Semi-structured interviews were conducted, transcribed, and thematically analysed in a reflexive manner. RESULTS: Five participants consented. Ten sub-themes emerged, which were organised into three main themes: service tensions, patient needs and practitioner feelings. CONCLUSION: Clinicians highly valued the new MS ‘pelvic health clinic’. Knowing that there was a service available empowered clinicians to ask patients about sexual health needs. Specific referral criteria may help further develop the service and improve patient care. Staff welcome training and support in this area or the option to signpost onwards; either mechanism lends itself to enhancing MS patient needs

Polynomial whitening for high-dimensional data

The inverse square root of a covariance matrix is often desirable for performing data whitening in the process of applying many common multivariate data analysis methods. Direct calculation of the inverse square root is not available when the covariance matrix is either singular or nearly singular, as often occurs in high dimensions. We develop new methods, which we broadly call polynomial whitening, to construct a low-degree polynomial in the empirical covariance matrix which has similar properties to the true inverse square root of the covariance matrix (should it exist). Our method does not suffer in singular or near-singular settings, and is computationally tractable in high dimensions. We demonstrate that our construction of low-degree polynomials provides a good substitute for high-dimensional inverse square root covariance matrices, in both

Simplicial and minimal-variance distances in multivariate data analysis

In this paper, we study the behaviour of the so-called k-simplicial distances and k-minimal-variance distances between a point and a sample. The family of k-simplicial distances includes the Euclidean distance, the Mahalanobis distance, Oja’s simplex distance and many others. We give recommendations about the choice of parameters used to calculate the distances, including the size of the sub-sample of simplices used to improve computation time, if needed. We introduce a new family of distances which we call k-minimal-variance distances. Each of these distances is constructed using polynomials in the sample covariance matrix, with the aim of providing an alternative to the inverse covariance matrix, that is applicable when data is degenerate. We explore some applications of the considered distances, including outlier detection and clustering, and compare how the behaviour of the distances is affected for different parameter choices

A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74

Photoreversible interconversion of a phytochrome photosensory module in the crystalline state.

A major barrier to defining the structural intermediates that arise during the reversible photointerconversion of phytochromes between their biologically inactive and active states has been the lack of crystals that faithfully undergo this transition within the crystal lattice. Here, we describe a crystalline form of the cyclic GMP phosphodiesterases/adenylyl cyclase/FhlA (GAF) domain from the cyanobacteriochrome PixJ in Thermosynechococcus elongatus assembled with phycocyanobilin that permits reversible photoconversion between the blue light-absorbing Pb and green light-absorbing Pg states, as well as thermal reversion of Pg back to Pb. The X-ray crystallographic structure of Pb matches previous models, including autocatalytic conversion of phycocyanobilin to phycoviolobilin upon binding and its tandem thioether linkage to the GAF domain. Cryocrystallography at 150 K, which compared diffraction data from a single crystal as Pb or after irradiation with blue light, detected photoconversion product(s) based on Fobs - Fobs difference maps that were consistent with rotation of the bonds connecting pyrrole rings C and D. Further spectroscopic analyses showed that phycoviolobilin is susceptible to X-ray radiation damage, especially as Pg, during single-crystal X-ray diffraction analyses, which could complicate fine mapping of the various intermediate states. Fortunately, we found that PixJ crystals are amenable to serial femtosecond crystallography (SFX) analyses using X-ray free-electron lasers (XFELs). As proof of principle, we solved by room temperature SFX the GAF domain structure of Pb to 1.55-Å resolution, which was strongly congruent with synchrotron-based models. Analysis of these crystals by SFX should now enable structural characterization of the early events that drive phytochrome photoconversion

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell–based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology

Evidence-based practice education for healthcare professions: an expert view

Internationally, evidence-based practice (EBP) is recognised as a foundational element of healthcare professional education. Achieving competency in this area is a complex undertaking that is reflected in disparities between ‘best EBP’ and actual clinical care. The effective development and implementation of professional education to facilitate EBP remains a major and immediate challenge. To ascertain nuanced perspectives on the provision of EBP education internationally, interviews were conducted with five EBP education experts from the UK, Canada, Australia and New Zealand. Definitive advice was provided in relation to (1) EBP curriculum considerations, (2) teaching EBP and (3) stakeholder engagement in EBP education. While a considerable amount of EBP activity throughout health profession education is apparent, effectively embedding EBP throughout curricula requires further development, with a ‘real-world’ pragmatic approach that engenders dialogue and engagement with all stakeholders required