Re-meandering attenuates frequent high-flows and diversifies physical habitat in a gravel-bed river

Channel re-meandering is commonly used in river restoration. However, few investigations have combined multi-temporal, reach-scale data from hydrological and topographic monitoring, and hydraulic numerical modelling to evaluate this restoration approach, particularly for low to medium energy gravel-bed rivers in low sediment supply settings. The Eddleston Water project focuses on the application and evaluation of Natural Flood Management measures to reduce flood risk to downstream communities and improve riverine physical habitat; providing a natural laboratory to examine re-meandering. A 1.6 km section of river was re-meandered between 2013 and 2016, increasing river length by 18 %. Assessment of the impact on flood attenuation was made using analysis of hydrological time series (2011–2020), comparing repeat (2018 and 2020) reach-scale topographic surveys of the channels to map geomorphic change, and numerically modelling two-dimensional flood extents and dynamics for flood events of different magnitude. Hydrological analysis showed enhanced flow attenuation was only statistically significant for in-channel events. Numerical hydraulic modelling showed a small impact on flood attenuation for a Q5 event (<15 min peak travel time delay, <1.2 % peak attenuation); effects were just discernible for a Q20 event. Repeat topographic surveys and sediment budgets identified overall bed degradation but showed physical habitat diversity was maintained. Whilst hydraulic effects were relatively small, they should be considered in the context of re-meandering being only undertaken on a small proportion of the river network. However, insights from hydraulic modelling show re-meandering design must consider interactions between channel and floodplain topography to maximise connectivity and thus attenuation

Consumer‐grade UAV solid‐state LiDAR accurately quantifies topography in a vegetated fluvial environment

To accompany a journal article in Earth Surface Processes & Landforms (ESPL) which details an investigation into the data quality and limitations of using the DJI L1 solid-state LiDAR system at both a controlled test location (Garscube Sports Fields, Glasgow, Scotland) and also in a geomorphic environment (River Feshie, Highlands, Scotland). Included are the following datasets (further detailed in readme file): • Point Clouds o Garscube – 4 x raw, unthinned o Feshie – 6 x thinned to 15cm density o Terrestrial Laser Scanning – 7 x gravel comparison patches • Digital Elevation Model o River Feshie only (see Figure 10 of article) • GNSS points o Garscube – GCPs & Football pitch markings o Feshie – GCPs, check points and vegetatio

An Adaptive Antiretroviral Therapy Adherence Intervention for Youth with HIV Through Text Message and Cell Phone Support with and without Incentives: A Sequential Multiple Assignment Randomized Trial (SMART)

Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months. Those with VL \u3c 200 or adherence \u3e 80% after the initial 3 months were rerandomized to usual care or 3 months of tapered, 2x/week CPS or SMS. Self-reported adherence and VLs were collected every 3 months for one year. Eighty-three youth were recruited with 81% identifying as cisgender males, 55% Black, 22% Latine/x, and 76% gay, and 56% recruited from the Southern US. Both cohorts initially randomized to CPS and SMS demonstrated significant improvements in adherence over the 12-months (P \u3c.001). Participants randomized to CPS had significant improvements in 7-day self-reported adherence over 12 months compared to those on SMS (P \u3c.027). Those receiving a tapered intervention for an additional 3 months had improved self-reported adherence compared to those randomized to the standard of care arm (P \u3c.001). Both SMS and CPS appear to be effective interventions for youth with poor antiretroviral adherence. Tapering the intervention for an additional 3 months is useful in maintaining adherence after the initial intervention. Additional research is required to determine how to best sequence these interventions, including the use of incentives

Dominant NARS1 mutations causing axonal Charcot-Marie-Tooth disease expand NARS1-associated diseases

Pathogenic variants in six aminoacyl-tRNA synthetase (ARS) genes are implicated in neurological disorders, most notably inherited per- ipheral neuropathies. ARSs are enzymes that charge tRNA molecules with cognate amino acids. Pathogenic variants in asparaginyl- tRNA synthetase (NARS1) cause a neurological phenotype combining developmental delay, ataxia and demyelinating peripheral neur- opathy. NARS1 has not yet been linked to axonal Charcot–Marie–Tooth disease. Exome sequencing of patients with inherited periph- eral neuropathies revealed three previously unreported heterozygous NARS1 variants in three families. Clinical and electrophysiological details were assessed. We further characterized all three variants in a yeast complementation model and used a knock-in mouse model to study variant p.Ser461Phe. All three variants (p.Met236del, p.Cys342Tyr and p.Ser461Phe) co-segregate with the sensorimotor axonal neuropathy phenotype. Yeast complementation assays show that none of the three NARS1 variants support wild-type yeast growth when tested in isolation (i.e. in the absence of a wild-type copy of NARS1), consistent with a loss-of-function effect. Similarly, the homo- zygous knock-in mouse model (p.Ser461Phe/Ser472Phe in mouse) also demonstrated loss-of-function characteristics. We present three previously unreported NARS1 variants segregating with a sensorimotor neuropathy phenotype in three families. Functional studies in yeast and mouse support variant pathogenicity. Thus, NARS1 is the seventh ARS implicated in dominant axonal Charcot–Marie–Tooth disease, further stressing that all dimeric ARSs should be evaluated for Charcot–Marie–Tooth disease

Confirmed 6-Month Disability Improvement and Worsening Correlate with Long-term Disability Outcomes in Alemtuzumab-Treated Patients with Multiple Sclerosis: Post Hoc Analysis of the CARE-MS Studies.

INTRODUCTION In the 2-year CARE-MS trials (NCT00530348; NCT00548405) in patients with relapsing-remitting multiple sclerosis, alemtuzumab showed superior efficacy versus subcutaneous interferon beta-1a. Efficacy was maintained in two consecutive extensions (NCT00930553; NCT02255656). This post hoc analysis compared disability outcomes over 9 years among alemtuzumab-treated patients according to whether they experienced confirmed disability improvement (CDI) or worsening (CDW) or neither CDI nor CDW. METHODS CARE-MS patients were randomized to receive two alemtuzumab courses (12 mg/day; 5 days at baseline; 3 days at 12 months), with additional as-needed 3-day courses in the extensions. CDI or CDW were defined as ≥ 1.0-point decrease or increase, respectively, in Expanded Disability Status Scale (EDSS) score from core study baseline confirmed over 6 months, assessed in patients with baseline EDSS score ≥ 2.0. Improved or stable EDSS scores were defined as ≥ 1-point decrease or ≤ 0.5-point change (either direction), respectively, from core study baseline. Functional systems (FS) scores were also assessed. RESULTS Of 511 eligible patients, 43% experienced CDI and 34% experienced CDW at any time through year 9 (patients experiencing both CDI and CDW were counted in each individual group); 29% experienced neither CDI nor CDW. At year 9, patients with CDI had a -0.58-point mean EDSS score change from baseline; 88% had stable or improved EDSS scores. Improvements occurred across all FS, primarily in sensory, pyramidal, and cerebellar domains. Patients with CDW had a +1.71-point mean EDSS score change; 16% had stable or improved EDSS scores. Patients with neither CDI nor CDW had a -0.10-point mean EDSS score change; 98% had stable or improved EDSS scores. CONCLUSION CDI achievement at any point during the CARE-MS studies was associated with improved disability at year 9, highlighting the potential of alemtuzumab to change the multiple sclerosis course. Conversely, CDW at any point was associated with worsened disability at year 9

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504–32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer’s disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentatothalamo- motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome

Low serum levels of 25-hydroxyvitamin D (25(OH)D), and low sunlight exposure, are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomised 1:1:1:1 to placebo, 1000, 5000, or 10 000 IU of oral vitamin D3 daily within each study centre (n=23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the HRs (95%CI) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre, and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions, and use of steroids, the HRs (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. Trial registration Australian Clinical Trials Registration Number ACTRN12612001160820

Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort