bluuebunny/crossref_metadata_2025 huggingface dataset:
UropathogenicEscherichia colipopulation structure and antimicrobial susceptibility in Norfolk, UK
Authors: Carter Cailean , Hutchison Alexandra , Rudder Steven , Trotter Elizabeth , Waters Emma , Elumogo Ngozi , Langridge Gemma C.
Published: March 2023

Synopsis

Background

Half of all women have experienced a urinary tract infection (UTI) in their lifetime and this remains a persistent issue in rural counties like Norfolk, UK. In alignment globally, UropathogenicE. coli(UPEC) are the main etiological agent for UTIs in Norfolk and are increasingly difficult to treat due to multi-drug resistance (MDR).

Objective

We set out to identify which clonal groups and resistance genes are disseminating in the community and hospitals in Norfolk, the first study of its kind for UPEC in this region.

Methods

We collected 217 clinicalE. coliisolates causing UTIs in the community and hospital from the Clinical Microbiology laboratory at Norfolk and Norwich University Hospital. These were whole genome sequenced using the Illumina and MinION platforms forin silicomulti-locus sequence typing and antibiotic resistance determinant detection.

Results

The isolates were composed of 74 sequence types (STs); 8 lineages represented 57% of this population: ST73, ST12, ST69, ST131, ST404, ST95, ST127, and ST1193. Importantly, primary UTI screening deemed 8% of isolates to be MDR, with high rates of resistance to ampicillin (52.1%) and trimethoprim (36.2%) in hospitals. Of concern is the probable clonal expansion of MDR groups ST131 and ST1193 in hospitals and community settings with chromosomally encodedblaCTX-M-15,blaOXA-1, and aac(6’)-Ib-cr5.

Conclusions

The burden of reported UTIs in Norfolk is largely caused by non-MDR isolates. The UPEC population is continually evolving, and monitoring samples with consideration of sources will help reduce burden of disease.
TheHypolimnas misippusgenome supports a common origin of the W chromosome in Lepidoptera
Authors: Orteu Anna , McCarthy Shane A. , Hornett Emily A. , Gemmell Matthew R. , Reynolds Louise A. , Warren Ian A. , Gordon Ian J. , Hurst Gregory D. D. , Durbin Richard , Martin Simon H. , Jiggins Chris D.
Published: March 2023

Moths and butterflies (Lepidoptera) have a heterogametic sex chromosome system with females carrying ZW chromosomes and males ZZ. The lack of W chromosomes in early diverging lepidopteran lineages has led to the suggestion of an ancestral Z0 system in this clade and a B chromosome origin of the W. This contrasts with the canonical model of W chromosome evolution in which the W would have originated from the same homologous autosomal pair as the Z chromosome. Despite the distinct models proposed, the rapid evolution of the W chromosome has hindered the elucidation of its origin. Here, we present high-quality, chromosome-level genome assemblies of twoHypolimnasspecies (Hypolimnas missipusandHypolimnas bolina)and use theH. misippusassembly to explore the evolution of W chromosomes in butterflies and moths. We show that inH. misippusthe W chromosome has higher similarity to the Z chromosome than any other chromosome, which could suggest a possible origin from the same homologous autosome pair as the Z chromosome. However, using genome assemblies of closely related species (ditrysian lineages) containing assembled W chromosomes, we present contrasting evidence suggesting that the W chromosome might have evolved from a B chromosome instead. Crucially, by using a synteny analysis to infer homology, we show that W chromosomes are likely to share a common evolutionary origin in Lepidoptera. This study highlights the difficulty of studying the evolution of W chromosomes and contributes to better understanding its evolutionary origins.

Significance

Butterflies and moths have a sex determination system in which females carry two different sex chromosomes, Z and W, while males carry two copies of the Z. The evolutionary origin of the W chromosome has been elusive, with many possible scenarios being suggested, such as the independent evolution of W chromosomes in many butterfly and moth species. Here, we present genome assemblies of twoHypolimnasbutterfly species and use one of them to shed light on the evolution of the W chromosome. We show that W chromosomes across butterflies and moths are very similar which suggests a shared common origin.
Experimental heatwaves and warming cause distinctive community responses through their interactions with a novel species
Authors: Chen Jinlin , Lewis Owen T.
Published: March 2023

As mean temperatures increase and heatwaves become more frequent, species are expanding their distributions to colonise new habitats. The resulting novel species interactions will simultaneously shape the temperature-driven reorganization of resident communities. The interactive effects of climate change and climate change-facilitated invasion have rarely been studied in multi-trophic communities, and are likely to differ depending on the nature of the climatic driver (i.e. climate extremes or constant warming). We recreated under laboratory conditions a host-parasitoid community typical of high-elevation rainforest sites in Queensland, Australia, comprising fourDrosophilaspecies and two associated parasitoid species. We subjected these communities to climate change in the form of either heatwaves or constant warming, in combination with an invasion treatment involving a novel host species from lower-elevation habitats. The two parasitoid species were sensitive to both warming and heatwaves, while the demographic responses ofDrosophilaspecies were highly idiosyncratic, reflecting the combined effects of thermal tolerance, parasitism, competition, and facilitation. After multiple generations, heatwaves (but not constant warming) promoted the establishment of low-elevation species in upland communities. The introduction of this invading species correlated negatively with the abundance of one of the parasitoid species, leading to cascading effects on its hosts and their competitors. Our study, therefore, reveals differing, sometimes contrasting, impacts of extreme temperatures and constant warming on community composition. It also highlights how the scale and direction of climate impacts could be further modified by range-expanding species within a bi-trophic community network.
Alpha 9 integrin expression enables reconstruction of the spinal cord sensory pathway
Authors: Stepankova Katerina , Smejkalova Barbora , Machova Urdzikova Lucia , Haveliková Katerina , de Winter Fred , Suchankova Stepanka , Verhaagen Joost , Herynek Vit , Turecek Rostislav , Kwok Jessica , Fawcett James , Jendelova Pavla
Published: March 2023

Full recovery from spinal cord injury can only occur if the axon pathways connecting the brain and spinal cord regenerate and restore motor and sensory connections. Neither sensory nor motor axons can regenerate spontaneously in the spinal cord in mammals. This failure is partly due to the lack of suitable adhesion molecules on the sensory axons that allows them to interact with the environment of the damaged spinal cord. In this rat study, an integrin adhesion molecule along with its activator was expressed in sensory neurons using an adeno-associated viral (AAV) vector. Expression of these adhesion molecules allowed sensory axons to regenerate through the spinal cord injury and all the way back to the brainstem, restoring the sensory pathway. Treated animals regained touch sensation and sensory behaviours.

The integrin ligands in the injured spinal cord are tenascin-C and osteopontin, but adult PNS and CNS neurons lack receptors to them. Sensory neurons were transduced with α9 integrin, which combines with endogenous β1 as α9β1 (which is a tenascin/osteopontin receptor) together with the integrin activator kindlin-1. Regeneration from sensory neurons transduced with α9integrin and kindlin-1 was examined after C4 and after T10 dorsal column lesions with C6,7 and L4.5 sensory ganglia injected with AAV1 vectors. In animals treated with α9 integrin and kindlin-1, sensory axons regenerated through tenascin-C-expressing connective tissue strands and bridges across the lesion and then re-entered the CNS tissue.

Many axons regenerated rostrally to the level of the medulla. Regenerated axons were particularly visible at the border between white and grey matter in the dorsal cord. Stimulation of the median/sciatic nerve caused many neurons rostral to the injury to activate and express cFos. VGLUT1/2 staining indicated newly formed functional synapses above the lesion. Behavioural recovery was seen in heat, mechanical sensation and tape removal tests. Many axons regenerated from the thoracic lesions to the brainstem, a distance of 4-5 cm, equivalent to the length of 1 or 2 spinal segments in humans.
Evaluating the performance of machine learning methods for risk estimation of delirium in patients hospitalized from the emergency department
Authors: Mueller Brianna , Street W. Nick , Carnahan Ryan M. , Lee Sangil
Published: March 2023

Introduction

Delirium is a cerebral dysfunction seen commonly in the acute care setting. It is associated with increased mortality and morbidity and is frequently missed in the emergency department (ED) and inpatient care by clinical gestalt alone. Identifying those at risk of delirium may help prioritize screening and interventions in the hospital setting.

Objective

Our objective was to leverage electronic health records to identify a clinically valuable risk estimation model for prevalent delirium in patients being transferred from the ED to inpatient units.

Methods

This was a retrospective cohort study to develop and validate a risk model to detect delirium using patient data available from prior visits and ED encounter. Electronic health records were extracted for patients hospitalized from the ED between January 1, 2014, and December 31, 2020. Eligible patients were aged 65 or older, admitted to an inpatient unit from the emergency department, and had at least one DOSS assessment or CAM‐ICU recorded within 72 h of hospitalization. Six machine learning models were developed to estimate the risk of delirium using clinical variables including demographic features, physiological measurements, medications administered, lab results, and diagnoses.

Results

A total of 28,531 patients met the inclusion criteria with 8057 (28.4%) having a positive delirium screening within the outcome observation period. Machine learning models were compared using the area under the receiver operating curve (AUC). The gradient boosted machine achieved the best performance with an AUC of 0.839 (95% CI, 0.837–0.841). At a 90% sensitivity threshold, this model achieved a specificity of 53.5% (95% CI 53.0%–54.0%) a positive predictive value of 43.5% (95% CI 43.2%–43.9%), and a negative predictive value of 93.1% (95% CI 93.1%–93.2%). A random forest model and L1‐penalized logistic regression also demonstrated notable performance with AUCs of 0.837 (95% CI, 0.835–0.838) and 0.831 (95% CI, 0.830–0.833) respectively.

Conclusion

This study demonstrated the use of machine learning algorithms to identify a combination of variables that enables an estimation of risk of positive delirium screens early in hospitalization to develop prevention or management protocols.
The limitations of overtime limits to reduce long working hours: Evidence from the 2018 to 2021 working time reform in Korea
Authors: Carcillo Stéphane , Hijzen Alexander , Thewissen Stefan
Published: March 2023

This article provides a first assessment of the causal impact of the 2018–2021 reform in Korea meant to combat its long working‐hour culture. The reform consists of lowering the statutory limit on total weekly working hours from 68 to 52. We apply a difference‐in‐difference approach in which we take advantage of the stepwise implementation of the reform by firm size using individual‐level data. We present three main findings. First, the introduction of the 52‐h limit reduced but far from eliminated the incidence of working more than 52 h. Second, there is some evidence that the introduction led to a reallocation of working hours, with more employees shifting from working fulltime to working overtime within the new limit (41–52 h). Third, and more tentatively, this reallocation more likely took place within firms to account for fewer overtime hours worked by their employees, rather than within households to compensate for any income effects. Overall, our results show that a lower statutory limit can help to lessen a long working‐hour culture, but is an insufficient measure by itself to fully eradicate it.
Impact of pre‐existing type 2 diabetes with and without cardiovascular disease on patients with COVID‐19
Authors: Nguyen Chi , Crowe Christopher L. , Kuti Effie , Narsipur Nihal , Donato Bonnie , Pepe Rebecca S. , Djaraher Rachel , Seman Leo , Graeter Nancy , Power Thomas P. , Mehra Rinku , Willey Vincent J.
Published: March 2023

Aim

To compare adverse outcomes among COVID‐19 patients with pre‐existing type 2 diabetes (T2D) only, T2D and cardiovascular disease (CVD), or neither.

Methods

This retrospective cohort study used administrative claims, laboratory and mortality data from the HealthCore Integrated Research Database. Patients with COVID‐19 were identified from 3 January 2020 to 31 May 2021 and stratified by the presence of T2D and CVD. Outcomes included hospitalization, intensive care unit (ICU) admission, mortality and complications following COVID‐19 infection. Propensity score matching and multivariable analyses were performed.

Results

A total of 321 232 COVID‐19 patients were identified (21 651 T2D + CVD, 28 184 T2D only, and 271 397 neither) with a mean (SD) follow‐up of 5.4 (3.0) months. After matching, 6 967 patients were identified for each group, and residual baseline differences remained. Adjusted analyses showed that COVID‐19 patients with T2D + CVD were 59% more probable to be hospitalized, 74% more probable to be admitted to the ICU, and had a 26% higher mortality risk than those with neither. COVID‐19 patients with T2D only were 28% and 32% more probable to be admitted to the hospital and ICU than those with neither, respectively. Among all T2D + CVD patients, acute respiratory distress syndrome (31%) and acute kidney disease (24%) were observed.

Conclusion

Our study highlights the incrementally poorer outcomes associated with pre‐existing T2D + CVD in COVID‐19 patients compared with those without T2D/CVD and suggests consideration of a more optimal management approach in these patients.
On resistance: As evinced in Iranian political affairs
Authors: Shabani Omid P.
Published: March 2023

Along with fundamental rights such as liberty and property, the Declaration of the Rights of Man and of the Citizen in 1789 also envisions a right to resist oppression. Irrespective of one's place on the political spectrum, resistance has been employed as an alternative both to submission and to revolt. After briefly sketching a historical and theoretical account of resistance I propose two parallel sets of criteria to further characterize good resistance. I submit that the first set is normative (I call it emancipatory) and the second set is critical (meaning it can be empirically assessed). I further break this typology down as follows: (1) Resistance is emancipatory when it is (a) nonviolent, (b) progressive, and (c) civil; and (2) it is critical when it seeks to (a) change policies and practices that are unjust, and (b) empower citizens to enjoy their full rights. I show the usefulness of this scheme by applying it to the political situation in Iran and by evincing these criteria in three instances of resistance there. Thus, in this context, I argue, resistance is a preferable alternative to both revolution and reform.
Identification of ultrastructural and biochemical cuticular markers influencing temperature of ice nucleation in selected genotypes of corn
Authors: Hamilton Kaila , Rahman Tawhidur , Sadowski Jason , Karunakaran Chithra , Tanino Karen
Published: March 2023

Corn is an economically important yet frost‐sensitive crop, injured at the moment of ice nucleation. However, the influence of autumn temperatures on subsequent ice nucleation temperature is unknown. A 10‐day chilling treatment under phytotron conditions (“mild”, 18/6°C) or (“extreme”, 10/5°C) generated no‐visible damage but induced changes in the cuticle of the four genotypes in this study. The putatively more cold hardy Genotypes 884 and 959 leaves nucleated at colder temperatures compared to the more sensitive Genotypes 675 and 275. After chilling treatment, all four genotypes displayed warmer ice nucleation temperatures, with Genotype 884 expressing the largest shift to warmer nucleation temperatures. Cuticular hydrophobicity reduced while cuticular thickness remained unchanged under the chilling treatment. By contrast, under five‐week field conditions, cuticle thickness increased in all genotypes, with Genotype 256 expressing a significantly thinner cuticle. FTIR spectroscopy revealed increases in the spectral regions of cuticular lipids in all genotypes after phytotron chilling treatment, while those spectral regions decreased under field conditions. A total of 142 molecular compounds were detected, with 28 compounds significantly induced under either phytotron or field conditions. Of these, seven compounds were induced under both conditions (Alkanes C31–C33, Ester C44, C46, β‐amyrin, and triterpene). While clear differential responses were observed, chilling conditions preceding a frost modified physical and biochemical properties of the leaf cuticle under both phytotron and field conditions indicating this response is dynamic and could be a factor in selecting corn genotypes better adapted to avoiding frost with lower ice nucleation temperature.
Review of industry response to an earthquake in a large natural gas field: Raton Basin, Colorado
Authors: Macartney* Hal
Published: March 2023

This chapter is a narrative review of how an oil and gas company responded to an earthquake within their operating area, and it is offered as an example for others who might be contemplating what to do in a similar situation. The chapter describes a process and practical steps that help to manage the operational, regulatory, and other consequences of seismicity potentially attributable to industry activity, and ultimately the possibility of large and damaging earthquakes in the future. The process involved collecting high-quality (and proprietary) data, ongoing monitoring, and collaboration with regulators and science agencies. The outcome in this case was continuation of producing operations and a better understanding of local seismicity. This chapter does not address the seismicity in detail, or its cause, nor what studies found.
121 Viral & bacterial RNA transcripts of substantia nigra and olfactory bulb in parkinson disease
Authors: Kaye Steve , Abbott James , Gentleman Steve , Oertel Wolfgang , McClure Myra , Hawkes Christopher H
Published: March 2023

Introduction

It is known that several viral species can induce parkinsonism in animals and humans, but no specific virus has been discovered in the classical human form of PD.

Methods

To investigate this further, we used next generation sequencing (NGS) to analyse post-mortem transcriptomes of substantia nigra (SN) and olfactory bulb (OB) in four PD cases and four multiple sclerosis patients who acted as positive controls. Bioinformatic analysis of the data set removed the majority of human transcripts and the remaining sequence data were compared to existing viral sequence data sets to search for signature viral sequences.

Results

Despite high read numbers and good quality NGS data, no viral or bacterial transcripts could be identified from either of the tissues examined. The few matches to existing viral databases were to viruses which rarely, if ever, infect humans and no multiple hits (matches to more than one gene of the same virus) were observed. Similarly, no bacterial sequences were found although it should be noted the analysis was carried out at the mRNA level.

Conclusion

This small but detailed analysis provided no evidence of RNA viral signatures in the OB or SN in the four samples taken from Parkinson’s disease brains. It is still possible that other brain areas known to display Lewy body pathology may contain viral sequences.
132 Does the use of a patient passport improve patient care in MND? A qualitative study
Authors: Abdelgalil Reem , Gaur Akshay , Hewamadduma Channa
Published: March 2023

Background

Care provision for Motor Neurone Disease (MND) patients require a Multidisciplinary Team (MDT) approach. Healthcare Professionals (HCPs) and MND patients often find it challenging to communicate effectively. Communication is particularly difficult and discontinuous in patients with rapidly changing conditions such as MND. Patient Passports (PP) can be used as a tool to improve communication and patient experience. We studied the place of PP in MND care.

Aim

To explore the views of MND patients and staff involved in MND care regarding the use of PP.

Methods

MND patients (n=35) and staff involved in MND care were consulted using semi-structured interviews and focus group discussions.

Results

Overall, themes emerged overwhelmingly favoured the use of a MND passport. These include improvement in communication, standardising healthcare provision across different regions and allowing for greater coordination of care. The emergency care providers and community HCP felt the PP was paramount to communicate with the parent team. However, concern was raised for the need to tailor it to the patient.

Conclusion

The PP was recognised as a distinct need. However, to validate the above findings, wider MND patient/carer and HCP survey is necessary.
142 Influence of baseline OFF-time on opicapone efficacy in Parkinson’s disease patients with motor fluctuations
Authors: Korlipara P , Ferreira J , Gama H , Santos A , Ikedo F , Rocha J , Soares-Da-Silva P
Published: March 2023

Background

Opicapone (OPC), a novel once-daily peripheral COMT inhibitor, has shown to be safe and effective in reducing OFF-time in Parkinson’s disease (PD) patients with motor fluctuations.

Objective

To evaluate the efficacy of OPC in levodopa-treated PD patients with motor fluctuations and subdivided by their baseline OFF-time.

Methods

BIPARK-I was a multinational, multicentre, double-blind, 14–15-week, placebo and active-controlled study to evaluate the efficacy of OPC in PD patients with end-of-dose motor fluctuations. This post-hoc subgroup analysis investigated efficacy of OPC 50 mg and entacapone (ENT), in levodopa-treated PD patients who were subdivided by baseline OFF-time (>90 mins and every additional 30 mins interval up to an interval with minimum sample size of 40 patients per active arm).

Results

Subjects with higher baseline OFF-times had a greater response under both OPC 50 mg and ENT with an average difference of -26.6 mins OFF-time reduction favouring OPC 50 mg. The estimated difference increased with increasing baseline OFF-time, reaching statistically significance (p<0.05) for subjects with >390 mins baseline OFF-time.

Conclusion

Higher baseline OFF-time correlated with greater response for both OPC 50 mg and ENT. OPC 50 mg presented a greater OFF-time reduction than ENT for all subgroup intervals, reaching statistically significance for subjects with >390 mins baseline OFF-time.
148 Longitudinal resting state changes in parkinson’s disease
Authors: Naidu Saadnah , Xing Lily Yue , Mohammadi-Nejad Ali-Reza , Sotiropoulos Stamatios , Auer Dorothee
Published: March 2023

Introduction

There is currently no objective method of monitoring progression of Parkinson’s disease (PD). We demonstrate resting-state magnetic resonance imaging (rs-MRI) as a potential biomarker of PD progression.

Methods

15 patients with idiopathic PD (age at baseline: mean±std, 66.43±7.16 years; follow-up: 69.46±7.09; Male, 10; H&Y baseline: 1.9±0.63; follow-up: 2.2±1.08) were recruited. Baseline and follow-up visits occurred 3.03± 0.18 years apart (Disease duration baseline: 3.61±1.33; follow-up: 6.64±1.38). (Disease severity: MDS-UPDRS-III baseline 27.17±15.28; follow-up: 35.53±16.45).

Image acquisition

rs-MRI was performed using 3T GE 750 MRI; 32-channel head coil; TR=2000ms; TE=30ms; Eyes open, medicated.

Analysis

An in-house optimised standardised pipeline was used based on FSL (1), MRIQC algorithm (2). Functional connectivity (FC) was derived from the following seeds (5 mm radius): primary motor cortex (M1), anterior and posterior putamen, caudate, supplementary motor area (SMA) and substantia nigra (SN). (Coordinates determined using AAL template and FSL atlas). Z score >2.3 used to report significance in a paired t test.

Results

Overall, we found greater FC at baseline vs follow-up in the motor cortex and SN, while FC with the posterior putamen and SMA showed a dissociated pattern of increased and decreased FC changes with disease progression.

Conclusion

Our preliminary analysis of a longitudinal dataset of >2 years mean duration show promising change patterns in line with progressive motor cortex and SN disconnection and complex putaminal and SMA disconnection.
163 Development of clinical and patient-reported quality metrics for multiple sclerosis: a UK pilot study report
Authors: Giovannoni Gavin , White Sarah , Mistry Niraj , Calhoun Samantha , Young Carolyn , Coutts Mhairi , Roberts Megan , Anderson Philip , Bernstein Rachel , Hobart Jeremy
Published: March 2023

Background

Quality standards (QS) for people with multiple sclerosis (PwMS) are suboptimal, ambiguous and restricted to certain patient subgroups and care pathways.

Aim

Develop and pilot MS metrics measuring service provision quality to identify areas for improvement.

Methods

A multidisciplinary Working Group developed clinician and patient-reported metrics and standardised data collection forms through an iterative process.

Results

Metrics covered: referral; diagnosis; treatment; annual review; general management; education. Pilot (n=76) showed: 31% of PwMS were referred to MS specialist within 4 weeks of suspected/confirmed demyelination; 28% and 56% had uncomplicated MS confirmed and were offered specialist MS nurse appointment, respectively, within 4 weeks of specialist referral; 75% of eligible PwMS were offered disease-modifying therapy within 8 weeks of confirmed MS diagnosis; 85% had comprehensive multidisciplinary team (MDT) annual review; 90% had a defined point of contact within the MS service; 86% of unscheduled contacts by PwMS, MDT or general practitioners were responded to within 3 days; 53% of MS services maintained a single database of PwMS; and 76% of PwMS were offered ongoing education. Data collection continues and updated findings will be reported.

Discussion

MS metrics/data forms are feasible for routine clinical settings, simple to interpret and provide a valuable benchmark for guiding MS service improvements.
198 A population study of temporal changes in MS disease modifying drug management and cost
Authors: McCarron Mark , Mullan Fiona , Hinchcliff Carol , McVerry Ferghal
Published: March 2023

Background

Multiple sclerosis (MS) management is changing. The prevalence of MS is increasing. We sought to investigate changes in disease modifying treatment (DMT) rates and costs in a defined population.

Methods

Among a population of 296,000 (Western Health and Social Care Trust) all MS patients taking DMTs were annually recorded including sequential DMT changes over an 11-year period (2008 to 2018 inclusive). Individual patient frequency of DMT switches were recorded. Drug costs were calculated over 10 years.

Results

From 2008 until 2018 there was more than a threefold increase in the number of MS patients taking a DMT (113 versus 394, Cochran-Armitage test for trend P<0.0001), representing by 2018 approximately 50% of all MS patients in this population. 216 patients switched drugs ranging from once (N=216) to 5 times (N=6 patients). Drug prices escalated sixfold from £832,351 in 2008 to £5,074,276 in 2018.

Conclusion

The increasing use of DMTs suggest that most NHS neurologists should become skilled in managing MS. As DMT coverage continues to increase in the MS population, drug costs should cover the funding of neurology teams to care for DMT-treated MS patients.
11.51 Stiff person and related syndromes: review of 21 patients and their response to treatment
Authors: Thompson Joseph , Sadalage Girija , Karim Abid , Jacob Saiju
Published: March 2023

Introduction

In patients with stiff person syndrome (SPS) and related syndromes the objective of treatment is to provide symptomatic relief from stiffness and spasms. Intravenous immunoglobulin (IVIG) therapy is a commonly prescribed treatment for SPS patients, however there is no widely used method of assessing the effectiveness of IVIG treatment in SPS. This issue has been addressed by the introduction of the Birmingham Response to IVIG Treatment (BRIT) scale.

Methods

Data from 21 patients was retrospectively analysed to explore a number of outcomes including: time to diagnosis, antibody statuses, clinical phenotype, first symptom, distribution of stiffness and EMG changes and treatments received.

9/21 patients had pre- and post-IVIG BRIT data, which was analysed using paired t-tests.

Results

Average time from first presentation to diagnosis was 37 months (range: 1–180 months). Anti-GAD antibody was positive in 18/21 (85.7%) with two glycine positive and one seronegative patient. EMG changes were found in 5/15 (33.3%) of patients.

Both functional ability score (p=0.0422) and quality of life score (p=0.0175) improved with statistical significance after receiving IVIG treatment.

Conclusion

IVIG treatment is effective in improving quality of life and functional ability in SPS patients. Treatment response can be comprehensively measured using the BRIT scale.
013 Spinal cord biopsy in neuromyelitis optica: a case report
Authors: Corbin David OC , Gill John , Caires Geoff de , William Jacqueline , Torre Matthew Gregory
Published: March 2023

We report a case of longitudinal extensive myelopathy (LEM) in a previously-well 31-year old male electrician who presented with a 2-month history of progressive bilateral weakness of the lower limbs, urinary difficulty and constipation. There were flexor spasms at the hips, ankle clonus, and Hoffman’s, but no cranial nerve, signs. Pain sensation was reduced below the nipples. MRI images showed expansion of the spinal cord from C3 to T2, with extensive T2 abnormalities, irregular post-contrast enhancement and cystic changes, suggesting a radiological diagnosis of pilocytic astrocytoma. Laminectomy at C3/C4 revealed no tumour. Biopsies were taken where an enhancing lesion was seen on the MRI study. Histopathology revealed gliotic changes affecting white matter tracts, with foci of chronic inflammation containing scattered CD3+ T, and rare CD20+ B, lymphocytes. There was no evidence of malignancy. HIV, syphilis, and HTLV-I serologic studies were negative. The patient was treated with prednisolone and azathioprine and was ambulant unassisted 18 months later. Serologic studies for anti-AQP4 IgG autoantibodies were unavailable at the time of presentation, but were subsequently found to be positive in the patient’s serum. While LEM is frequently seen in neuromyelitis optica, very few cases of the spinal cord pathology have been published.
020 A fluey man – a reason for neurologists to remain vigilant
Authors: Singh Neena , Gimson Amy , Dobson Ruth
Published: March 2023

Case

We present a 64 year old gentleman with previous non-metastatic melanoma and newly diagnosed myeloma, for which he had received steroids but not chemotherapy. He developed fever followed by an ascending acute flaccid paralysis with brainstem involvement, requiring ventilatory support within hours of onset. MRI demonstrated an extensive enhancing longitudinal spinal cord lesion with signal change in thalami, temporal lobes and pons. CSF protein was >6 g, WCC 150 (90% neutrophils), no organisms and negative virology. Neurophysiology demonstrated a selective motor neuropathy/neuronopathy.

H1N1-influenza A (‘swine flu’) RNA was detected on nasopharyngeal aspirate. He was treated with Zanamavir, antimicrobials, steroids, and plasma exchange. His clinical improvement remains slow, and he will require long-term care.

Discussion

This patient developed a rare, catastrophic neurological complication of pandemic FluA, in the context of untreated multiple myeloma. Whilst not a pure acute flaccid myelitis, this case highlights the need to be aware of uncommon neurological complications of viral infections.

There has been a peak in 2018 of cases of acute flaccid myelitis across the UK, Europe, and America. Public Health England has declared a national incident in response to this. The cause remains unproven, and neurologists should report suspected cases to PHE.
024 Electronic intervention to improve acute neurology referral system
Authors: Routledge Emma , Ziff Oliver , Jarman Paul , Turner Chris , Chandratheva Arvind
Published: March 2023

Introduction

There is conflicting viewpoints regarding phone versus email referral systems within acute neurology.

Methods

Our study evaluates the referrals system at University College London Hospital. We assessed how effective the pre-existing phone system was at managing referrals and compared this to a newly implemented email system. Over a month period the neurology phone call-log was interrogated. We recorded incoming and outgoing calls (missed and received), timing and call duration. After the email system was implemented, we assessed the email-logs over a month period.

Results

With the phone system nighty nine incoming and 54 outgoing calls were recorded. Of these, 63% incoming calls were missed and 37% outgoing calls were not answered. Fridays were the busiest day of the week with 33% of the total calls (6% Mondays, 22% Tuesdays, 20% Wednesday, 19% Thursday). Most calls were received between 09:00 – 10:00 (25% of total) & 16:00 – 17:00 (22% of total). With the email system, 45 referrals were received electronically. Of these, all were responded to within 24 hours.

Conclusions

The phone referral system was not fit for purpose with 63% of incoming calls missed. The electronic system was associated with far-reaching improvements in managing referrals.
031 Managing rituximab delivery in a neurosciences centre
Authors: Dorsey R , Williams T , Singh-Curry V , Johnson M , Pritchard J , Muraro P , Nicholas R
Published: March 2023

Rituximab has potential indications in neurology not as yet studied in RCTs making access difficult but also means that there is no coherent process to ensure useful outcome data is acquired. In addition alternatives such as immunoglobulins now have limited availability. We set up a multidisciplinary team (MDT) to establish appropriate indication for rituximab, and ensure consistency of administration and outcome data collection.

Data from neurosciences in Imperial Healthcare NHS Trust was audited (6/2010–4/2018). After completing a systematic review a MDT was initiated with peripheral nerve, epilepsy, and neuroinflammatory experts. The MDT was then audited (4/2018–1/2019).

79 subjects were assessed: mean age 49.7±15.4 years (range 19–80yrs). 42 (5.4 per year) were treated since 2010 and 29 since the MDT began (34.8 per year). The commonest diagnoses were limbic encephalitis (17) and vasculitis (12). Subjects had on average 2.8 immune therapies prior to treatment. 21/71 had PLEX and 23/71 had immunoglobulins. Prior to the MDT inception 65% of subject reported positive outcomes. After the MDT 8 (19%) were rejected and there was minimal use in those without a clear diagnosis.

Subjects who receive rituximab often have a series of in-hospital complex expensive therapies prior to treatment. A rituximab MDT increases its use in appropriate groups.
043 A specialist cognitive clinic for the deaf community
Authors: Harris Matthew , Au Darica , Judd Katy , Atkinson Joanna , Mummery Catherine
Published: March 2023

Background

Early dementia diagnosis is crucial to ensure timely treatment and support. Approximately 100,000 people in the UK are Deaf and use British Sign Language as their first language. For this population access to healthcare can be difficult, clinical assessment challenging and misdiagnosis may occur.

In August 2011, a specialist cognitive clinic for the Deaf community was established at the National Hospital for Neurology and Neurosurgery. We sought to evaluate this service to inform future provision of care.

Methods

We retrospectively analysed electronic patient records from August 2011 until December 2018.

Results

36 patients were reviewed aged 35–83 years (median 71.5). 83% of those referred did not have a prior diagnosis. 17% had previously been given a provisional diagnosis, however this was changed in 67% of cases following review in our clinic.

All patients underwent neuropsychological assessment and in 92% cranial imaging was performed. 8% additionally underwent FDG-PET and 25% lumbar puncture. 47% were diagnosed with a neurodegenerative disorder (Alzheimer’s Disease in 77%), 6% mild cognitive impairment, 11% a pre-existing neurological disorder and 19% with subjective memory complaints without evidence of neurodegeneration.

Donepezil was commenced in all patients diagnosed with Alzheimer’s disease. 9% experienced adverse effects and changed medication.

Conclusion

In this evaluation, we found that Deaf patients had difficulties obtaining an accurate diagnosis prior to clinic and we observed a high proportion of neurodegenerative and neurological diagnoses (64%) compared to other cognitive clinics (reportedly 40–50%). We believe these results highlight the challenges Deaf patients have in accessing healthcare and this underscores the importance of this service in ensuring patients receive an accurate and timely diagnosis.
069 Progressive multifocal leukoencephalopathy in good’s syndrome
Authors: Edwards M , Cousins R , Smith R , Hinds NP
Published: March 2023

A 65-year-old retired paramedic presented with progressive visual disturbance, cognitive impairment and behavioural change over a course of 3 months. At the time of admission he was cortically blind and disoriented to time, place and person. His past medical history included a recently resected thymoma. An MRI Head with contrast revealed bilateral white matter signal change mainly in occipital lobes extending to both temporal and parietal lobes. This was non-enhancing with no obvious oedema. His basic CSF parameters were normal and JCV antibodies werenegative. However his CSF JCV PCR was significantly high and consistent with a diagnosis of progressive multifocal leukoencephalopathy (PML). HIV testing was negative and he was not taking any immunosuppressive therapy. The patient was found to be hypogammaglobulinaemic as well having a low B-cell count. In the context of a thymoma this was a case of Good’s syndrome. Unfortunately the patient deteriorated further due to a hospital acquired pneumonia and he was palliated prior to his death. PML is a rare diagnosis and most often related to HIV or immunosuppression. It has been reported in cases of hypogammaglobulinaemia but this is thought to be one of only a handful of cases of PML in Good’s syndrome.
083 Facial twitching, breathlessness and fever: an unexpected and potentially lethal triad
Authors: Mbizvo Gashirai K , Lentell Isabel , Leen Clifford , Roddie Huw , Derry Chris , Duncan Susan , Rannikmäe Kristiina
Published: March 2023

Background

We describe a patient co-presenting with epilepsia partialis continua (EPC), disseminated tuberculosis (TB), and hemophagocytic lymphohistiocytosis (HLH).

Case

A 54-year-old lady presented with facial twitching, breathlessness, and night sweats. Clinical examination revealed pyrexia and continuous, stereotyped, right-sided facial contractions. These worsened with speech and continued through sleep. A clinical diagnosis of EPC was made (video provided). CT imaging of the chest and serous fluid analyses were consistent with a diagnosis of disseminated Mycobacterium tuberculosis, with a left motor strip tuberculoma evident on post-contrast MRI brain. An additional diagnosis of HLH was made following the identification of pancytopenia and hyperferritinaemia on peripheral blood, with hemophagocytosis evident on bone marrow investigation (pathology slides provided). She was extremely unwell and hospitalised for six months, including two admissions to intensive care for invasive ventilation. She was treated successfully with high doses of antiepileptic drugs, 12 months of oral anti-TB therapy, and chemotherapy with eight weeks of etoposide and dexamethasone for HLH, followed by 12 months of ciclosporin and prednisolone.

Conclusions

Presentation with this triad is rare – to our knowledge, this is the first documented case. A lack of evidence surrounding the co-expression of this triad may represent absolute rarity or, more likely, clinical failure to recognise the triad (resulting in early death from untreated TB/HLH). Therefore, the case helps improve education around how such a patient may present and be managed.
Painlevé equations, integrable systems and the stabilizer set of Virasoro orbit
Authors: Cariñena José F. , Guha Partha , Rañada Manuel F.
Published: March 2023

We study a geometrical formulation of the nonlinear second-order Riccati equation (SORE) in terms of the projective vector field equation on [Formula: see text], which in turn is related to the stability algebra of Virasoro orbit. Using Darboux integrability method, we obtain the first integral of the SORE and the results are applied to the study of its Lagrangian and Hamiltonian descriptions. Using these results, we show the existence of a Lagrangian description for SORE, and the Painlevé II equation is analyzed.
Large N two-dimensional Yang–Mills fields for the spectral behavior of Brownian particles and relativistic many-body systems
Authors: Ganesan Timothy
Published: March 2023

This work explores the spectral behavior of interacting many-body systems — gravitating dust solutions (galaxy formations and black hole clusters) and Brownian fluids. The eigenvalue dynamics of these systems are then represented by the two-dimensional Yang–Mills field (i.e. spectral projection). The interacting particles in the many-body systems are associated with random matrices of dimensions, N. The Painlevé II dynamical system is shown to surface at large N ([Formula: see text]); when the mentioned Yang–Mills field is configured in a specific way. Critical phenomena (Douglas–Kazakov phase transition) of the interacting many-body systems at large N were attained via the spectral projection of the mentioned physical systems. In addition, the existence of instantons (spectral Dirac monopoles) in the strong coupling phase was shown during phase transition.
Numerical Investigation of Reducing Wave Propagation Hazard Utilizing an Appropriate Vegetation Area
Authors: Ziaadini-Dashtekhaki Maryam , Ghaeini-Hessaroeyeh Mahnaz , Hamzehei-Javaran Saleh
Published: March 2023

In this study, a numerical model was employed to determine the optimal location for vegetation as an environmentally friendly method of attenuating tsunami waves. The governing equations are shallow water equations solved using shock-capturing schemes with second-order accuracy model. This simulation was validated using experimental data and another numerical model for simulating the propagation of tsunami waves on a vegetated horizontal bed and vegetated sloping beach. The parameters of wave damping rate, maximum velocity, and height for the plant area at various locations and vegetation zone lengths were investigated using numerical models. By increasing the length of the plant zone, the height and velocity of the tsunami wave were reduced, and the wave damping was increased. The examination of various locations and lengths of the plant area demonstrated that the plant area’s distance from the shoreline is a significant factor in coastal protection. The results exhibit that the location of the forest area has a great impact on the control of destructive factors along the beach. As a result, this study provides some information for designing a tsunami-resistant forest area.
Almost Optimal Exact Distance Oracles for Planar Graphs
Authors: Charalampopoulos Panagiotis , Gawrychowski Paweł , Long Yaowei , Mozes Shay , Pettie Seth , Weimann Oren , Wulff-Nilsen Christian
Published: March 2023

We consider the problem of preprocessing a weighted directed planar graph in order to quickly answer exact distance queries. The main tension in this problem is between
space
S
and
query time
Q
, and since the mid-1990s all results had polynomial time-space tradeoffs, e.g.,
Q
= ~ Θ(
n/√ S
) or
Q
= ~Θ(

n
5/2
/S
3/2

).

In this article we show that there is no polynomial tradeoff between time and space and that it is possible to
simultaneously
achieve almost optimal space
n

1+
o
(1)

and almost optimal query time
n

o
(1)

. More precisely, we achieve the following space-time tradeoffs:

n

1+
o
(1)

space and log

2+
o
(1)

n
query time,

n
log

2+
o
(1)

n
space and
n

o
(1)

query time,

n

4/3+
o
(1)

space and log

1+
o
(1)

n
query time.

We reduce a distance query to a variety of
point location
problems in additively weighted
Voronoi diagrams
and develop new algorithms for the point location problem itself using several partially persistent dynamic tree data structures.
Supplementary Data from Local Radiotherapy Induces Homing of Hematopoietic Stem Cells to the Irradiated Bone Marrow
Authors: Bastianutto Carlo , Mian Asim , Symes Julie , Mocanu Joseph , Alajez Nehad , Sleep Gillian , Shi Wei , Keating Armand , Crump Michael , Gospodarowicz Mary , Medin Jeff , Minden Mark , Liu Fei-Fei
Published: March 2023

Supplementary Data from Local Radiotherapy Induces Homing of Hematopoietic Stem Cells to the Irradiated Bone Marrow
Supplementary Table 1, Figure Legends 1-5 from Integrative Microarray Analysis of Pathways Dysregulated in Metastatic Prostate Cancer
Authors: Setlur Sunita R. , Royce Thomas E. , Sboner Andrea , Mosquera Juan-Miguel , Demichelis Francesca , Hofer Matthias D. , Mertz Kirsten D. , Gerstein Mark , Rubin Mark A.
Published: March 2023

Supplementary Table 1, Figure Legends 1-5 from Integrative Microarray Analysis of Pathways Dysregulated in Metastatic Prostate Cancer
Supplementary Figure Legends 1-3, Table 1 from Elevated CRAF as a Potential Mechanism of Acquired Resistance to BRAF Inhibition in Melanoma
Authors: Montagut Clara , Sharma Sreenath V. , Shioda Toshi , McDermott Ultan , Ulman Matthew , Ulkus Lindsey E. , Dias-Santagata Dora , Stubbs Hannah , Lee Diana Y. , Singh Anurag , Drew Lisa , Haber Daniel A. , Settleman Jeffrey
Published: March 2023

Supplementary Figure Legends 1-3, Table 1 from Elevated CRAF as a Potential Mechanism of Acquired Resistance to BRAF Inhibition in Melanoma
Supplementary Table 4 from MicroRNA Signatures in Human Ovarian Cancer
Authors: Iorio Marilena V. , Visone Rosa , Di Leva Gianpiero , Donati Valentina , Petrocca Fabio , Casalini Patrizia , Taccioli Cristian , Volinia Stefano , Liu Chang-Gong , Alder Hansjuerg , Calin George A. , Ménard Sylvie , Croce Carlo M.
Published: March 2023

Supplementary Table 4 from MicroRNA Signatures in Human Ovarian Cancer
Supplementary Figure 4 from Targeting the Nuclear Factor-κB Rescue Pathway Has Promising Future in Human Renal Cell Carcinoma Therapy
Authors: Sourbier Carole , Danilin Sabrina , Lindner Véronique , Steger Jacques , Rothhut Sylvie , Meyer Nicolas , Jacqmin Didier , Helwig Jean-Jacques , Lang Hervé , Massfelder Thierry
Published: March 2023

Supplementary Figure 4 from Targeting the Nuclear Factor-κB Rescue Pathway Has Promising Future in Human Renal Cell Carcinoma Therapy
Supplementary Figure 2 from Targeting the Nuclear Factor-κB Rescue Pathway Has Promising Future in Human Renal Cell Carcinoma Therapy
Authors: Sourbier Carole , Danilin Sabrina , Lindner Véronique , Steger Jacques , Rothhut Sylvie , Meyer Nicolas , Jacqmin Didier , Helwig Jean-Jacques , Lang Hervé , Massfelder Thierry
Published: March 2023

Supplementary Figure 2 from Targeting the Nuclear Factor-κB Rescue Pathway Has Promising Future in Human Renal Cell Carcinoma Therapy