On February 24, 2022, Russia launched a full-scale invasion of Ukraine that dominated headlines around the world. Millions of Ukrainians would flee the country, and a third of the population would be ...displaced. In the days following the invasion, Swedish migration expert Gregg Bucken-Knapp sent text messages to his Ukrainian colleagues, offering support and assistance. These were their responses. In a series of graphic vignettes, Messages from Ukraine takes the words of Ukrainian migration professionals and transforms them into snapshots of how war affects the lives of everyday people: those who are forced to flee home and seek safety elsewhere, those who choose to stay and volunteer or fight, those who witness events unfolding from afar, and those who find themselves trapped in cities under siege. Messages from Ukraine captures a moment in time to tell a timeless story about war, displacement, determination, and resilience. Proceeds from the sale of Messages from Ukraine will go to the Canada-Ukraine Foundation, a national charitable foundation that provides humanitarian aid to the people of Ukraine.
The war in Ukraine has altered the course of global history. These authors explore how.When Vladimir Putin's forces sought to conquer Ukraine in February 2022, they did more than threaten the ...survival of a vulnerable democracy. The invasion unleashed a crisis that has changed the course of world affairs. This conflict has reshaped alliances, deepened global cleavages, and caused economic disruptions that continue to reverberate around the globe. It has initiated the first great-power nuclear crisis in decades and raised fundamental questions about the sources of national power and military might in the modern age. The outcome of the conflict will profoundly influence the international balance of power, the relationship between democracies and autocracies, and the rules that govern global affairs. In War in Ukraine, Hal Brands brings together an all-star cast of analysts to assess the conflict's origins, course, and implications and to offer their appraisals of one of the most geopolitically consequential crises of the early twenty-first century. Essays cover topics including the twists and turns of the war itself, the successes and failures of US strategy, the impact of sanctions, the future of Russia and its partnership with China, and more.Contributors: Anne Applebaum, Joshua Baker, Alexander Bick, Hal Brands, Daniel Drezner, Peter Feaver, Lawrence Freedman, Francis Gavin, Brian Hart, William Inboden, Andrea Kendall-Taylor, Michael Kimmage, Michael Kofman, Stephen Kotkin, Mark Leonard, Bonny Lin, Thomas Mahnken, Dara Massicot, Michael McFaul, Robert Person, Kori Schake, and Ashley Tellis.
IntroductionSporadic CJD (sCJD) is universally fatal. While median survival is 5 months, there is consider- able heterogeneity with some surviving weeks while others survive several months or years. ...We sought to evaluate characteristics influencing disease duration, and the performance of latest diagnostic criteria incorporating cortical ribboning on MRI brain and the RT-QuIC assay.Methods501 autopsy-confirmed cases from surveillance centres in the UK, France, Germany and Italy were stratified into short (<75 days), typical (75-222 days) and long (>222 days) survival groups. We evaluated clinical features, investigation results, and diagnostic criteria classification.ResultsShort survival was associated with male sex (p=0.02) and older age (p=0.004). Prion protein gene codon 129 polymorphism status greatly influenced duration (p=<0.001, with longest survival in methionine- valine heterozygotes). Extrapyramidal features were most frequent in long survivors (p=0.04). EEG and 14-3-3 were most sensitive with short survival (p<0.001), RT-QuIC with typical survival (p=0.03) and MRI sen- sitivity did not vary (p=0.4). Previous diagnostic criteria lacked sensitivity in long survivors (p=0.001) while updated criteria were equivalent between groups (p=0.19): sensitivity for long survivors increased 27.7%.ConclusionsThis study demonstrates important factors influencing survival and associated phenotypes. The latest diagnostic criteria for sCJD have significantly enhanced diagnosis in long survivors.
IntroductionDisruption to clinical services, triggered by the COVID-19 pandemic, led to extended intervals between ocrelizumab treatments for some patients.ObjectivesTo assess the rates of developing ...low immunoglobulin levels and timing of CD19+ B-cell count repopulation in a real-world clinical population. To assess for evidence of clinical or radiological MS disease activity with extended interval dosing of ocrelizumab.MethodsWe audited 712 patients given ocrelizumab by our seven clinical services. All monitoring of immunoglobulin levels and CD19+ cell counts were recorded. Disease activity was defined as on treatment clinical relapse, radiological activity, and EDSS progression.ResultsLow immunoglobulin levels developed in 102 patients, the odds ratio for developing hypogam- maglobulinaemia comparing extended to standard interval dosing was 0.42 (CI 0.22-0.81). Disease activity included 20 participants with clinical relapses and 72 with new MRI lesions. There was no evidence of excess clinical or radiological disease activity on switching to extended interval dosing. 38 had EDSS progression, giving an odds ratio comparing extended to standard interval dosing of 0.77 (CI 0.38-1.56).ConclusionsThis real-world data of extended interval dosing of ocrelizumab indicates lower rates of hypogammaglobulinaemia and no detrimental effect on short-term treatment efficacy.
Trigeminal neuralgia is a common cause of facial pain, typically producing paroxysmal bursts of shooting pain in one or more divisions of the trigeminal nerve. Whilst it usually occurs as a primary ...phenomenon due to neurovascular conflict, secondary causes account for around 15% of cases, most commonly cerebellopontine angle tumours. Multiple sclerosis is another common secondary cause of presumed inflammatory aetiology.We report a case of trigeminal neuralgia in association with diffuse scleroderma. A 43 year old carpenter presented with typical symptoms of unilateral facial pain around a year after receiving a diagnosis of systemic sclerosis with seropositivity to Scl-70 and centromere antibodies. MR imaging at the time revealed enhancement of the left trigeminal nerve, which resolved on subsequent imaging six months later.The association of trigeminal neuralgia and diffuse scleroderma has previously been reported, with a recent case-control study providing novel evidence of a direct association between the two conditions. Nevertheless it represents a very rare cause in patients presenting to the neurology clinic. In this presen- tation we explore the subject of secondary trigeminal neuralgia and provide a précis of the up-to-date management for this painful condition.
Visual deterioration in Idiopathic Intracranial Hypertension (IIH) warrants surgical intervention. All patients with IIH admitted to St. George’s, London for 10-years from 2010 were identified and ...those with shunts were analyzed retrospectively. Of 1234 IIH patients, 27 had shunts, 12/27 were aged 19-30 and 24 were females. The most common indication for a shunt was quantifiable visual impairment (52%). Majority had lumboperitoneal shunts (67%). The average length of stay was 16 days (2SD+/-8 days). In the first 3 years, neurologists were not involved in the care of 11/27 patients but all since. The number of shunts per year peaked at 6 in 2013 and is now 1-2. At first follow-up, vision and headache improved in 84% and 85% of patients, respectively. 40% had recurrence of symptoms despite a functioning shunt due to coexisting migraine (36%), functional neurological disorder (9%) or both (18%). The most common complication was shunt obstruction (single-revision; 30%; multiple-revisions; 19%), followed by low-pressure symptoms (26%), requiring readmissions in 81% of patients. Shunting is not without risks but is currently indicated in those with deteriorating visual function; hence, the decision to proceed with shunting in IIH should be made with vigilance in accordance with the 2018 consensus guidelines.
RG6102 is a bispecific 2+1 monoclonal antibody (mAb) under development for the treatment of Alz- heimer’s disease (AD). It combines the anti-amyloid beta antibody gantenerumab with a transferrin ...receptor 1-binding “Brain Shuttle” module, enabling active receptor-mediated transport across the blood–brain barrier.In preclinical studies, RG6102 has shown superior distribution, target engagement and amyloid plaque clearance compared with gantenerumab. In a human Phase Ia study, there was a markedly increased cerebrospinal fluid (CSF)/plasma ratio for RG6102 compared with typical mAbs.Brainshuttle AD is a 28-week, randomised, global, multicentre, double-blind, placebo-controlled, parallel- group Phase Ib/IIa study evaluating the safety, tolerability, immunogenicity and pharmacokinetics/phar- macodynamics (PK/PD) of RG6102. Multiple-ascending intravenous doses of RG6102 are administered every 4 weeks to patients with prodromal or mild-to-moderate AD. The study consists of a screening period, a double-blind treatment period and a safety follow-up period.The primary objective is to evaluate the safety and tolerability of RG6102. Secondary outcome measures include the change from baseline in brain amyloid load, plasma and CSF concentration of RG6102 and incidence of anti-drug antibodies to RG6102. Exploratory endpoints include the clinical effect of multiple doses of RG6102 on clinical outcome measures and on various PD biomarkers.Recruitment for Brainshuttle AD is currently ongoing.
IntroductionHNPP is an autosomal dominant disorder with estimated prevalence between 0.84- 16/100,000, commonly presenting as mononeuropathies involving pressure-prone areas. Presentation as both a ...brachial plexopathy and spinal accessory neuropathy is rare, and previously unreported.Case ReportA 30-year old female with no known medical co-morbidities presented with a 3-month history of right shoulder pain and weakness, and intermittent numbness of the elbow and hand. Examina- tion showed wasting of right trapezius and spinati muscles, shoulder droop, and weakness involving the right sternocleidomastoid, shoulder, and median and ulnar-supplied hand muscles. Nerve conduction studies and electromyography revealed axonal-loss pattern neuropathy of right suprascapular and spinal accessory nerves. Focal demyelination was seen in bilateral median and ulnar nerves across the wrists and elbows. Needle EMG showed denervation changes in right infraspinatus and trapezius muscles. Sub- sequent genetic testing of patient and her mother revealed deletion of chromosome 17p11.2 including PMP22. She improved clinically following a period of intensive physiotherapy.ConclusionHNPP typically affects pressure-prone sites such as the median, ulnar or peroneal nerves. Brachial plexopathy is uncommon, and involvement of spinal accessory nerve is very rare. Recognition of symptoms, with appropriate targeted electrodiagnostic and genetic investigations is important in achieving an accurate diagnosis and management.
Genome-wide association studies (GWAS) of Multiple Sclerosis (MS) have focussed on populations of European ancestry. Studying MS genetics in other ancestries is necessary to ensure the ...generalisability of these findings.We report the design of a new collaborative MS genetics project – ‘ADAMS’. Individuals with MS from non-White-British ethnic backgrounds will be recruited either via a website – https://app.mantal.co.uk/ adams – or in-person at a participating site. We will collect demographic and phenotypic data using a combination of a baseline questionnaire and subsequent healthcare record linkage. We will collect DNA from up to 1000 participants using saliva kits (Oragene-600) and genotype individuals using the Illumina Global Screening Array version 3. Genotypes will be combined with large ancestrally-matched control datasets (UK Biobank and East London Genes and Health).We have recruited 91 participants within the first eight weeks of the study. Of this initial cohort, 73.9% are female, 84.5% were born in the UK, 32.4% identified as Asian or Asian British, 28.2% as Black, African, Caribbean or Black British, and the remainder identified as having mixed, other, or White backgrounds. 51% stated they were unlimited in their mobility. 84.7% of participants have relapse-onset forms of MS and 76.1% have ever had disease-modifying therapy. The median age at diagnosis is 30.5 and the median age at recruitment 36.7. Further recruitment and genetics results will follow over the next 3 years.
BackgroundLetters dictated by healthcare professionals in routine patient care form an invaluable dataset but are difficult to access and interpret. The UK MS Register (UKMSR) previously outlined ...(ABN2019) usage of Natural Language Processing Algorithms (NLP-A) to harvest and transform written language into analysable data in databases. We expanded the variables captured, increased the number of donating hospitals and compared the results to the previous NLP-A.AimApply the new NLP-A to a random letter selection and evaluate output and results.MethodsA random, seeded, selection algorithm chose 100 letters from a corpus of 2690 consented in/outpatient letters from 13 Trusts. Letters were reviewed by human domain experts for Date Of Birth, NHS Number, Gender, Clinic Date, Postcode, MS Type and Expanded Disability Status Score (EDSS). NLP-A was applied and assessment made against the same variables.ResultsRun time was 15.4s, Sensitivity and Specificity > 98% in all cases except Clinic Date (Sensitivity 87%, Specificity 20%), MSType (Sensitivity 84%, Specificity 98%) and Postcode (Sensitivity 100%, Specificity 66%). Low specificity in Clinic Date illustrates disagreement on criteria between reviewer and NLP-A. These results represent a 5% increase (in common variables) in Sensitivity and Specificity over the 2019 algorithm.ConclusionWe have improved the ability to accurately and rapidly identify required variables from the UKMSR minimum dataset using NLP-A. We are continuing to implement this on a widespread basis in the UKMSR.
