An anatomy-based lumped parameter model of cerebrospinal venous circulation: can an extracranial anatomical change impact intracranial hemodynamics?

Background The relationship between extracranial venous system abnormalities and central nervous system disorders has been recently theorized. In this paper we delve into this hypothesis by modeling the venous drainage in brain and spinal column areas and simulating the intracranial flow changes due to extracranial morphological stenoses. Methods A lumped parameter model of the cerebro-spinal venous drainage was created based on anatomical knowledge and vessels diameters and lengths taken from literature. Each vein was modeled as a hydraulic resistance, calculated through Poiseuille’s law. The inputs of the model were arterial flow rates of the intracranial, vertebral and lumbar districts. The effects of the obstruction of the main venous outflows were simulated. A database comprising 112 Multiple Sclerosis patients (Male/Female = 42/70; median age ± standard deviation = 43.7 ± 10.5 years) was retrospectively analyzed. Results The flow rate of the main veins estimated with the model was similar to the measures of 21 healthy controls (Male/Female = 10/11; mean age ± standard deviation = 31 ± 11 years), obtained with a 1.5 T Magnetic Resonance scanner. The intracranial reflux topography predicted with the model in cases of internal jugular vein diameter reduction was similar to those observed in the patients with internal jugular vein obstacles. Conclusions The proposed model can predict physiological and pathological behaviors with good fidelity. Despite the simplifications introduced in cerebrospinal venous circulation modeling, the key anatomical feature of the lumped parameter model allowed for a detailed analysis of the consequences of extracranial venous impairments on intracranial pressure and hemodynamics

The 2014-2017 outburst of the young star ASASSN-13db: A time-resolved picture of a very low-mass star between EXors and FUors

ASASSN-13db is a M5-type star with a protoplanetary disk, the lowest mass star known to experience accretion outbursts. Since its discovery in 2013, it has experienced two outbursts, the second of which started in November 2014 and lasted until February 2017. We use high- and low-resolution spectroscopy and time-resolved photometry from the ASAS-SN survey, the LCOGT and the Beacon Observatory to study the lightcurve and the dynamical and physical properties of the accretion flow. The 2014-2017 outburst lasted for nearly 800 days. A 4.15d period in the lightcurve likely corresponds to rotational modulation of a star with hot spot(s). The spectra show multiple emission lines with variable inverse P-Cygni profiles and a highly variable blueshifted absorption below the continuum. Line ratios from metallic emission lines (Fe I/Fe II, Ti I/Ti II) suggest temperatures of $\sim$5800-6000 K in the accretion flow. Photometrically and spectroscopically, the 2014-2017 event displays an intermediate behavior between EXors and FUors. The accretion rate (\.{M}=1-3$\times$10$^{-7}$M$_\odot$/yr), about 2 orders of magnitude higher than the accretion rate in quiescence, is not significantly different from the accretion rate observed in 2013. The absorption features in the spectra suggest that the system is viewed at a high angle and drives a powerful, non-axisymmetric wind, maybe related to magnetic reconnection. The properties of ASASSN-13db suggest that temperatures lower than those for solar-type stars are needed for modeling accretion in very low-mass systems. Finally, the rotational modulation during the outburst reveals that accretion-related structures settled after the begining of the outburst and can be relatively stable and long-lived. Our work also demonstrates the power of time-resolved photometry and spectroscopy to explore the properties of variable and outbursting stars. (Abridged)

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

Background: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. Methods: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. Findings: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. Interpretation: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. Funding: The UK National Institute for Health Research Health Technology Assessment Programme

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Exploring the dimming event of RW Aurigae A through multi-epoch VLT/X-shooter spectroscopy

Context. RW Aur A is a classical T Tauri star that has suddenly undergone three major dimming events since 2010. The reason for these dimming events is still not clear. Aims. We aim to understand the dimming properties, examine accretion variability, and derive the physical properties of the inner disc traced by the CO ro-vibrational emission at near-infrared wavelengths (2.3 μm). Methods. We compared two epochs of X-shooter observations, during and after the dimming. We modelled the rarely detected CO bandhead emission in both epochs to examine whether the inner disc properties had changed. The spectral energy distribution was used to derive the extinction properties of the dimmed spectrum and compare the infrared excess between the two epochs. Lines tracing accretion were used to derive the mass accretion rate in both states. Results. The CO originates from a region with physical properties of T = 3000 K, NCO = 1 × 1021 cm−2 and vk sin i = 113 km s−1. The extinction properties of the dimming layer were derived with the effective optical depth ranging from τeff ~2.5−1.5 from the UV to the near-IR. The inferred mass accretion rate Ṁacc is ~1.5 × 10−8 M⊙ yr−1 and ~2 × 10−8 M⊙ yr−1 after and during the dimming respectively. By fitting the spectral energy distribution, additional emission is observed in the infrared during the dimming event from dust grains with temperatures of 500–700 K. Conclusions. The physical conditions traced by the CO are similar for both epochs, indicating that the inner gaseous disc properties do not change during the dimming events. The extinction curve is flatter than that of the interstellar medium, and large grains of a few hundred microns are thus required. When we correct for the observed extinction, the mass accretion rate is constant in the two epochs, suggesting that the accretion is stable and therefore does not cause the dimming. The additional hot emission in the near-IR is located at about 0.5 au from the star and is not consistent with an occulting body located in the outer regions of the disc. The dimming events could be due to a dust-laden wind, a severe puffing-up of the inner rim, or a perturbation caused by the recent star-disc encounterEuropean Commission Horizon 2020European Research CouncilIrish Research CouncilScience Foundation IrelandEuropean Southern Observatory FellowshipPublished version is permitted without embargo - A

Exploring the dimming event of RW Aurigae A through multi-epoch VLT/X-shooter spectroscopy

Context. RW Aur A is a classical T Tauri star that has suddenly undergone three major dimming events since 2010. The reason for these dimming events is still not clear. Aims. We aim to understand the dimming properties, examine accretion variability, and derive the physical properties of the inner disc traced by the CO ro-vibrational emission at near-infrared wavelengths (2.3 μm). Methods. We compared two epochs of X-shooter observations, during and after the dimming. We modelled the rarely detected CO bandhead emission in both epochs to examine whether the inner disc properties had changed. The spectral energy distribution was used to derive the extinction properties of the dimmed spectrum and compare the infrared excess between the two epochs. Lines tracing accretion were used to derive the mass accretion rate in both states. Results. The CO originates from a region with physical properties of T = 3000 K, NCO = 1 × 1021 cm−2 and vk sin i = 113 km s−1. The extinction properties of the dimming layer were derived with the effective optical depth ranging from τeff ~2.5−1.5 from the UV to the near-IR. The inferred mass accretion rate Ṁacc is ~1.5 × 10−8 M⊙ yr−1 and ~2 × 10−8 M⊙ yr−1 after and during the dimming respectively. By fitting the spectral energy distribution, additional emission is observed in the infrared during the dimming event from dust grains with temperatures of 500–700 K. Conclusions. The physical conditions traced by the CO are similar for both epochs, indicating that the inner gaseous disc properties do not change during the dimming events. The extinction curve is flatter than that of the interstellar medium, and large grains of a few hundred microns are thus required. When we correct for the observed extinction, the mass accretion rate is constant in the two epochs, suggesting that the accretion is stable and therefore does not cause the dimming. The additional hot emission in the near-IR is located at about 0.5 au from the star and is not consistent with an occulting body located in the outer regions of the disc. The dimming events could be due to a dust-laden wind, a severe puffing-up of the inner rim, or a perturbation caused by the recent star-disc encounterEuropean Commission Horizon 2020European Research CouncilIrish Research CouncilScience Foundation IrelandEuropean Southern Observatory FellowshipPublished version is permitted without embargo - A