Automatic segmentation of hemorrhagic transformation on follow-up non-contrast CT after acute ischemic stroke.

Background: Hemorrhagic transformation (HT) following reperfusion therapies is a serious complication for patients with acute ischemic stroke. Segmentation and quantification of hemorrhage provides critical insights into patients' condition and aids in prognosis. This study aims to automatically segment hemorrhagic regions on follow-up non-contrast head CT (NCCT) for stroke patients treated with endovascular thrombectomy (EVT). Methods: Patient data were collected from 10 stroke centers across two countries. We propose a semi-automated approach with adaptive thresholding methods, eliminating the need for extensive training data and reducing computational demands. We used Dice Similarity Coefficient (DSC) and Lin's Concordance Correlation Coefficient (Lin's CCC) to evaluate the performance of the algorithm. Results: A total of 51 patients were included, with 28 Type 2 hemorrhagic infarction (HI2) cases and 23 parenchymal hematoma (PH) cases. The algorithm achieved a mean DSC of 0.66 ± 0.17. Notably, performance was superior for PH cases (mean DSC of 0.73 ± 0.14) compared to HI2 cases (mean DSC of 0.61 ± 0.18). Lin's CCC was 0.88 (95% CI 0.79-0.93), indicating a strong agreement between the algorithm's results and the ground truth. In addition, the algorithm demonstrated excellent processing time, with an average of 2.7 s for each patient case. Conclusion: To our knowledge, this is the first study to perform automated segmentation of post-treatment hemorrhage for acute stroke patients and evaluate the performance based on the radiological severity of HT. This rapid and effective tool has the potential to assist with predicting prognosis in stroke patients with HT after EVT.

Gene Flow and Isolation in the Arid Nearctic Revealed by Genomic Analyses of Desert Spiny Lizards.

The opposing forces of gene flow and isolation are two major processes shaping genetic diversity. Understanding how these vary across space and time is necessary to identify the environmental features that promote diversification. The detection of considerable geographic structure in taxa from the arid Nearctic has prompted research into the drivers of isolation in the region. Several geographic features have been proposed as barriers to gene flow, including the Colorado River, Western Continental Divide, and a hypothetical Mid-Peninsular Seaway in Baja California. However, recent studies suggest that the role of barriers in genetic differentiation may have been overestimated when compared to other mechanisms of divergence. In this study, we infer historical and spatial patterns of connectivity and isolation in Desert Spiny Lizards (Sceloporus magister) and Baja Spiny Lizards (S. zosteromus), which together form a species complex composed of parapatric lineages with wide distributions in arid western North America. Our analyses incorporate mitochondrial sequences, genomic-scale data, and past and present climatic data to evaluate the nature and strength of barriers to gene flow in the region. Our approach relies on estimates of migration under the multispecies coalescent to understand the history of lineage divergence in the face of gene flow. Results show that the S. magister complex is geographically structured, but we also detect instances of gene flow. The Continental Divide is a strong barrier to gene flow, while the Colorado River is more permeable. Analyses yield conflicting results for the catalyst of differentiation of peninsular lineages in S. zosteromus. Our study shows how large-scale genomic data for thoroughly sampled species can shed new light on biogeography. Furthermore, our approach highlights the need for the combined analysis of multiple sources of evidence to adequately characterize the drivers of divergence.

Functional outcomes of patients with ischaemic stroke with known atrial fibrillation not on therapeutic anticoagulation.

BACKGROUND: Anticoagulation significantly reduces the risk of ischaemic stroke in patients with atrial fibrillation (AF). There are a proportion of patients with known AF who remain off anticoagulation. Aims This study aims to retrospectively compare the baseline characteristics, treatments and functional outcomes between patients with ischaemic stroke and known AF based on their anticoagulation status. METHODS: A single-centre, retrospective review of consecutive patients with an ischaemic stroke and a known history of AF was conducted. RESULTS: Two hundred four patients with an ischaemic stroke had documented AF prior to the index admission, of which 126 were anticoagulated. Median admission National Institutes of Health Stroke Scale score was lower for anticoagulated patients, though not statistically significant (5.1 vs 7.0, P = 0.09). Median baseline modified Rankin score (mRS) did not significantly differ. Nonanticoagulated patients were more likely to have large vessel occlusions (37.2% vs 23.8%, P = 0.04) and more likely to receive intravenous thrombolysis (15.4% vs 1.6%, P < 0.01). There was no difference in rates of endovascular clot retrieval between groups (P > 0.05). Unfavourable functional outcome at 90 days (mRS ≥ 3) did not significantly differ between groups (P = 0.51). A total of 38.5% of nonanticoagulated patients had no documented reason for this. Of the patients who survived the index admission, 81.5% of patients who were not anticoagulated on admission received anticoagulation. CONCLUSIONS: Baseline anticoagulation was associated with milder stroke severity in ischaemic stroke patients with known AF. There was no significant difference in functional outcomes at 90 days between groups. Larger observational studies are required to further assess this cohort.

Risk factors of hemorrhagic transformation in acute ischaemic stroke: A systematic review and meta-analysis.

Background: Hemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)]. Methods: Electronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated. Results: A total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212-5.599, I 2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041-1.272, I 2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970-7.591, I 2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060-1.105, I 2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001-1.005, I 2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565-0.833, I 2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012-1.866, I 2 = 86.4%) were predictors of sICH after EVT. Conclusion: Several predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.

Total and Subgenomic RNA Viral Load in Patients Infected With SARS-CoV-2 Alpha, Delta, and Omicron Variants.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear. METHODS: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in specimens from 3204 individuals hospitalized with coronavirus disease 2019 (COVID-19) at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression. RESULTS: Mean Ct values at presentation for N were 24.14 (SD 4.53) for non-variants of concern, 25.15 (SD 4.33) for Alpha, 25.31 (SD 4.50) for Delta, and 26.26 (SD 4.42) for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants. CONCLUSIONS: RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements add little information for the purposes of estimating infectivity.

Prior anticoagulation and bridging thrombolysis improve outcomes in patients with atrial fibrillation undergoing endovascular thrombectomy for anterior circulation stroke.

BACKGROUND: Where stroke occurs with pre-existing atrial fibrillation (AF)studies validating the safety and efficacy of bridging thrombolysis, and the use of endovascular thrombectomy (EVT) in the setting of prior anticoagulation, are limited to single-center reports. METHODS: In a retrospective analysis, AF patients undergoing EVT for anterior circulation large vessel occlusion stroke enrolled in a prospectively-maintained, international multicenter database (International Stroke Perfusion Imaging Registry (INSPIRE)) between 2016 and 2019 were studied. Patients were categorized by anticoagulation status: anticoagulated (warfarin/non-vitamin K oral anticoagulants) versus not anticoagulated. Patients not anticoagulated were further divided into intravenous thrombolysis versus no thrombolysis. Outcomes compared between groups included 90-day modified Rankin Scale, 90-day mortality, rates of symptomatic intracerebral hemorrhage (sICH), and good reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3). RESULTS: Of 563 AF patients, 118 (21%) were on anticoagulation. AF patients on anticoagulation showed improved 90-day functional outcomes (adjusted odds ratio (aOR) 1.68, 95% confidence interval (95% CI) 1.00 to 2.82). Mortality (26.3% vs 23.8%), sICH (4.5% vs 3.9%), and rates of good reperfusion (91.3% vs 88.0%) were similar between those anticoagulated and those not anticoagulated. Thrombolysis before EVT in AF patients was independently associated with improved 90-day functional outcomes (aOR 1.81, 95% CI 1.18 to 2.79) and reduced mortality (aOR 0.51, 95% CI 0.31 to 0.84), with similar sICH rates (3.4% vs 4.5%). CONCLUSIONS: Anticoagulated patients with AF who underwent EVT had improved 90-day functional outcomes and similar sICH rates. Thrombolysis before EVT in AF patients was associated with improved 90-day functional outcomes and reduced mortality.

Organellar DNA continues to provide a rich source of information in the genomics era.

The genomics revolution continues to change how ecologists and evolutionary biologists study the evolution and maintenance of biodiversity. It is now easier than ever to generate large molecular data sets consisting of hundreds to thousands of independently evolving nuclear loci to estimate a suite of evolutionary and demographic parameters. However, any inferences will be incomplete or inaccurate if incorrect taxonomic identities and perpetuated throughout the analytical pipeline. Due to decades of research and comprehensive online databases, sequencing and analysis of mitochondrial DNA (mtDNA), chloroplast DNA (cpDNA) and select nuclear genes can provide researchers with a cost effective and simple means to verify the species identity of samples prior to subsequent phylogeographic and population genomic analysis. The addition of these sequences to genomic studies can also shed light on other important evolutionary questions such as explanations for gene tree-species tree discordance, species limits, sex-biased dispersal patterns, adaptation, and mtDNA introgression. Although the mtDNA and cpDNA genomes often should not be used exclusively to make historical inferences given their well-known limitations, the addition of these data to modern genomic studies adds little cost and effort while simultaneously providing a wealth of useful data that can have significant implications for both basic and applied research.

Mobile App to Enhance Patient Activation and Patient-Provider Communication in Major Depressive Disorder Management: Collaborative, Randomized Controlled Pilot Study.

BACKGROUND: Enhanced patient-provider engagement can improve patient health outcomes in chronic conditions, including major depressive disorder (MDD). OBJECTIVE: We evaluated the impact of a digitally enabled care mobile app, Pathway, designed to improve MDD patient-provider engagement. Patients used a mobile interface to assess treatment progress and share this information with primary care providers (PCPs). METHODS: In this 52-week, real-world effectiveness and feasibility study conducted in primary care clinics, 40 patients with MDD who were recently prescribed antidepressant monotherapy were randomized to use a mobile app with usual care (20/40, 50%) or usual care alone (20/40, 50%). Patients in the app arm engaged with the app daily for 18 weeks; a report was generated at 6-week intervals and shared with the PCPs to facilitate shared treatment decision-making discussions. The patients discontinued the app at week 18 and were followed through year 1. Coprimary outcome measures, assessed via research visits, included change from baseline in the 13-item Patient Activation Measure (PAM-13) and 7-item Patient-Provider Engagement Scale scores at week 18. Additional outcome measures included depression severity (9-item Patient Health Questionnaire [PHQ-9]) and cognitive symptoms (5-item Perceived Deficits Questionnaire-Depression). RESULTS: All 37 patients (app arm: n=18, 49%; usual care arm: n=19, 51%) who completed the 18-week follow-up period (n=31, 84% female, mean age 36, SD 11.3 years) had moderate to moderately severe depression. Improvements in PAM-13 and PHQ-9 scores were observed in both arms. Increases in PAM-13 scores from baseline to 18 weeks were numerically greater in the app arm than in the usual care arm (mean 10.5, SD 13.2 vs mean 8.8, SD 9.4; P=.65). At 52 weeks, differences in PAM-13 scores from baseline demonstrated significantly greater improvements in the app arm than in the usual care arm (mean 20.2, SD 17.7 vs mean 1.6, SD 14.2; P=.04). Compared with baseline, PHQ-9 scores decreased in both the app arm and the usual care arm at 18 weeks (mean 7.8, SD 7.2 vs mean 7.0, SD 6.5; P=.73) and 52 weeks (mean 9.5, SD 4.0 vs mean 4.7, SD 6.0; P=.07). Improvements in 7-item Patient-Provider Engagement Scale and WHO-5 scores were observed in both arms at 18 weeks and were sustained through 52 weeks in the app arm. Improvements in WHO-5 scores at 52 weeks were significantly greater in the app arm than in the usual care arm (41.5 vs 20.0; P=.02). CONCLUSIONS: Patients with MDD will engage with a mobile app designed to track treatment and disease progression. PCPs will use the data generated as part of their assessment to inform clinical care. The study results suggest that an app-enabled clinical care pathway may enhance patient activation and benefit MDD management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03242213; https://clinicaltrials.gov/ct2/show/NCT03242213.

Characterising persons diagnosed with HIV as either recent or long-term using a cross-sectional analysis of recent infection surveillance data collected in Malawi from September 2019 to March 2020.

OBJECTIVES: In Malawi, a recent infection testing algorithm (RITA) is used to characterise infections of persons newly diagnosed with HIV as recent or long term. This paper shares results from recent HIV infection surveillance and describes distribution and predictors. SETTING: Data from 155 health facilities in 11 districts in Malawi were pooled from September 2019 to March 2020. PARTICIPANTS: Eligible participants were ≥13 years, and newly diagnosed with HIV. Clients had RITA recent infections if the rapid test for recent infection (RTRI) test result was recent and viral load (VL) ≥1000 copies/mL; if VL was <1000 copies/mL the RTRI result was reclassified as long-term. Results were stratified by age, sex, pregnancy/breastfeeding status and district. RESULTS: 13 838 persons consented to RTRI testing and 12 703 had valid RTRI test results and VL results after excluding clients not newly HIV-positive, RTRI negative or missing data (n=1135). A total of 12 365 of the 12 703 were included in the analysis after excluding those whose RTRI results were reclassified as long term (n=338/784 or 43.1%). The remainder, 446/12 703 or 3.5%, met the definition of RITA recent infection. The highest percentage of recent infections was among breastfeeding women (crude OR (COR) 3.2; 95% CI 2.0 to 5.0), young people aged 15-24 years (COR 1.6; 95% CI 1.3 to 1.9) and persons who reported a negative HIV test within the past 12 months (COR 3.3; 95% CI 2.6 to 4.2). Factors associated with recent infection in multivariable analysis included being a non-pregnant female (adjusted OR (AOR) 1.4; 95% CI 1.2 to 1.8), a breastfeeding female (AOR 2.2; 95% CI 1.4 to 3.5), aged 15-24 years (AOR 1.6; 95% CI 1.3 to 1.9) and residents of Machinga (AOR 2.0; 95% CI 1.2 to 3.5) and Mzimba (AOR 2.4; 95% CI 1.3 to 4.5) districts. CONCLUSIONS: Malawi's recent HIV infection surveillance system demonstrated high uptake and identified sub-populations of new HIV diagnoses with a higher percentage of recent infections.

Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting.

BACKGROUND: Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. METHODS: Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. RESULTS: During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8-77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9-58.3], P<0.001). No difference was observed between specificities of NCCT+CTA and NCCT+CTA+CTP (98.7% [95% CI, 98.5-100] versus 98.7% [95% CI, 96.9-99.6], P=0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1-77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5-2.7mL). CONCLUSIONS: Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.

Video head impulse testing to differentiate vestibular neuritis from posterior circulation stroke in the emergency department: a prospective observational study.

Background and aims: Vertigo is a common presentation to the emergency department (ED) with 5% of presentations due to posterior circulation stroke (PCS). Bedside investigations such as the head impulse test (HIT) are used to risk stratify patients, but interpretation is operator dependent. The video HIT (v-HIT) provides objective measurement of the vestibular-ocular-reflex (VOR) and may improve diagnostic accuracy in acute vestibular syndrome (AVS). We aimed to evaluate the use of v-HIT as an adjunct to clinical assessment to acutely differentiate vestibular neuritis (VN) from PCS. Methods: 133 patients with AVS were consecutively enrolled from the ED of our comprehensive stroke centre between 2018 and 2021. Patient assessment included a targeted vestibular history, HINTs examination (Head Impulse, Nystagmus and Test of Skew), v-HIT and MRI>48 hours after symptom onset. The HINTS/v-HIT findings were analysed and compared between VN, PCS and other cause AVS. Clinical course, v-HIT and MRI findings were used to determine diagnosis. Results: Final diagnosis was VN in 40%, PCS 15%, migraine 16% and other cause AVS 29%. PCS patients were older than VN patients (mean age 68.5±10.6 vs 60.1±14.2 years, p=0.14) and had more cardiovascular risk factors (3 vs 2, p=0.002). Mean VOR gain was reduced (<0.8) in ipsilateral horizontal and (<0.7) anterior canals in VN but was normal in PCS, migraine and other cause AVS. V-HIT combined with HINTs was 89% sensitive and 96% specific for a diagnosis of VN. Conclusions V-HIT combined with HINTs is a reliable tool to exclude PCS in the ED.

Cerebrovascular Disease Profiles of Culturally and Linguistically Diverse Communities in South Western Sydney and New South Wales.

INTRODUCTION: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). METHODS: This was a 10-year retrospective analysis (2011-2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. RESULTS: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. DISCUSSION/CONCLUSION: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Incidence of COVID-19 reinfection among Midwestern healthcare employees.

Given the overwhelming worldwide rate of infection and the disappointing pace of vaccination, addressing reinfection is critical. Understanding reinfection, including longevity after natural infection, will allow us to better know the prospect of herd immunity, which hinges on the assumption that natural infection generates sufficient, protective immunity. The primary objective of this observational cohort study is to establish the incidence of reinfection of COVID-19 among healthcare employees who experienced a prior COVID-19 infection over a 10-month period. Of 2,625 participants who experienced at least one COVID-19 infection during the 10-month study period, 156 (5.94%) experienced reinfection and 540 (20.57%) experienced recurrence after prior infection. Median days were 126.50 (105.50-171.00) to reinfection and 31.50 (10.00-72.00) to recurrence. Incidence rate of COVID-19 reinfection was 0.35 cases per 1,000 person-days, with participants working in COVID-clinical and clinical units experiencing 3.77 and 3.57 times, respectively, greater risk of reinfection relative to those working in non-clinical units. Incidence rate of COVID-19 recurrence was 1.47 cases per 1,000 person-days. This study supports the consensus that COVID-19 reinfection, defined as subsequent infection ≥ 90 days after prior infection, is rare, even among a sample of healthcare workers with frequent exposure.

A Multicentre Study Comparing Cerebrovascular Disease Profiles in Pacific Islander and Caucasian Populations Presenting with Stroke and Transient Ischaemic Attack.

INTRODUCTION: In a multicentre study, we contrasted cerebrovascular disease profiles in Pacific Island (PI)-born patients (Indigenous Polynesian [IP] or Indo-Fijian [IF]) presenting with transient ischaemic attack (TIA), ischaemic stroke (IS) or intracerebral haemorrhage (ICH) with those of Caucasians (CSs). METHODS: Using a retrospective case-control design, we compared PI-born patients with age- and gender-matched CS controls. Consecutive patients were admitted to 3 centres in South Western Sydney (July 2013-June 2020). Demographic and clinical data studied included vascular risk factors, stroke subtypes, and imaging characteristics. RESULTS: There were 340 CS, 183 (27%) IP, and 157 (23%) IF patients; mean age 65 years; and 302 (44.4%) female. Of these, 587 and patients presented with TIA/IS and 93 (13.6%) had ICH. Both IP and IF patients were significantly more likely to present >24 h from symptom onset (odds ratios [ORs] vs. CS 1.87 and 2.23). IP patients more commonly had body mass indexes >30 (OR 1.94). Current smoking and excess alcohol intake were higher in CS. Hypertension, diabetes, and chronic kidney disease were significantly higher in both IP and IF groups in comparison to CS. IP patients had higher rates of AF and those with known AF were more commonly undertreated than both IF and CS patients (OR 2.24, p = 0.007). ICH was more common in IP patients (OR 2.32, p = 0.005), while more IF patients had intracranial arterial disease (OR 5.10, p < 0.001). DISCUSSION/CONCLUSION: Distinct cerebrovascular disease profiles are identifiable in PI-born patients who present with TIA or stroke symptoms in Australia. These may be used in the future to direct targeted approaches to stroke prevention and care in culturally and linguistically diverse populations.

Genome-Scale Data Reveal Deep Lineage Divergence and a Complex Demographic History in the Texas Horned Lizard (Phrynosoma cornutum) throughout the Southwestern and Central United States.

The southwestern and central United States serve as an ideal region to test alternative hypotheses regarding biotic diversification. Genomic data can now be combined with sophisticated computational models to quantify the impacts of paleoclimate change, geographic features, and habitat heterogeneity on spatial patterns of genetic diversity. In this study, we combine thousands of genotyping-by-sequencing (GBS) loci with mtDNA sequences (ND1) from the Texas horned lizard (Phrynosoma cornutum) to quantify relative support for different catalysts of diversification. Phylogenetic and clustering analyses of the GBS data indicate support for at least three primary populations. The spatial distribution of populations appears concordant with habitat type, with desert populations in AZ and NM showing the largest genetic divergence from the remaining populations. The mtDNA data also support a divergent desert population, but other relationships differ and suggest mtDNA introgression. Genotype-environment association with bioclimatic variables supports divergence along precipitation gradients more than along temperature gradients. Demographic analyses support a complex history, with introgression and gene flow playing an important role during diversification. Bayesian multispecies coalescent analyses with introgression (MSci) analyses also suggest that gene flow occurred between populations. Paleo-species distribution models support two southern refugia that geographically correspond to contemporary lineages. We find that divergence times are underestimated and population sizes are overestimated when introgression occurred and is ignored in coalescent analyses, and furthermore, inference of ancient introgression events and demographic history is sensitive to inclusion of a single recently admixed sample. Our analyses cannot refute the riverine barrier or glacial refugia hypotheses. Results also suggest that populations are continuing to diverge along habitat gradients. Finally, the strong evidence of admixture, gene flow, and mtDNA introgression among populations suggests that P. cornutum should be considered a single widespread species under the General Lineage Species Concept.

SARS-CoV-2 Genomic Surveillance Reveals Little Spread From a Large University Campus to the Surrounding Community.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had high incidence rates at institutions of higher education (IHE) in the United States, but the transmission dynamics in these settings are poorly understood. It remains unclear to what extent IHE-associated outbreaks have contributed to transmission in nearby communities. METHODS: We implemented high-density prospective genomic surveillance to investigate these dynamics at the University of Michigan and the surrounding community during the Fall 2020 semester (August 16-November 24). We sequenced complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from 1659 individuals, including 468 students, representing 20% of cases in students and 25% of total cases in Washtenaw County over the study interval. RESULTS: Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community. CONCLUSIONS: The largest outbreaks among students at the University of Michigan did not significantly contribute to the rise in community cases in Fall 2020. These results provide valuable insights into SARS-CoV-2 transmission dynamics at the regional level.

Nitrous oxide-induced myeloneuropathy.

BACKGROUND AND PURPOSE: Nitrous oxide misuse is a recognized issue worldwide. Prolonged misuse inactivates vitamin B12, causing a myeloneuropathy. METHODS: Twenty patients presenting between 2016 and 2020 to tertiary hospitals in Sydney with myeloneuropathy due to nitrous oxide misuse were reviewed. RESULTS: The average age was 24 years, and mean canister consumption was 148 per day for 9 months. At presentation, paresthesias and gait unsteadiness were common, and seven patients were bedbound. Mean serum B12 was normal (258 pmol/L, normal range [NR] = 140-750) as was active B12 (87 pmol/L, normal > 35). In contrast, mean serum homocysteine was high (51 µmol/L, NR = 5-15). Spinal magnetic resonance imaging (MRI) showed characteristic dorsal column T2 hyperintensities in all 20 patients. Nerve conduction studies showed a predominantly axonal sensorimotor neuropathy (n = 5). Patients were treated with intramuscular vitamin B12, with variable functional recovery. Three of the seven patients who were bedbound at presentation were able to walk again with an aid at discharge. Of eight patients with follow-up data, most had persistent paresthesias and/or sensory ataxia. Mobility scores at admission and discharge were not significantly correlated with the serum total and active B12 levels or cumulative nitrous oxide use. There were no significant trends between serum active B12 level and cumulative nitrous oxide use (Spearman rho = -0.331, p = 0.195). CONCLUSIONS: Nitrous oxide misuse can cause a severe but potentially reversible subacute myeloneuropathy. Serum and active B12 can be normal, while elevated homocysteine and dorsal column high T2 signal on MRI strongly suggest the diagnosis. Neurological deficits can improve with abstinence and B12 supplementation, even in the most severely affected patients.

The effects of climate and demographic history in shaping genomic variation across populations of the Desert Horned Lizard (Phrynosoma platyrhinos).

Species often experience spatial environmental heterogeneity across their range, and populations may exhibit signatures of adaptation to local environmental characteristics. Other population genetic processes, such as migration and genetic drift, can impede the effects of local adaptation. Genetic drift in particular can have a pronounced effect on population genetic structure during large-scale geographic expansions, where a series of founder effects leads to decreases in genetic variation in the direction of the expansion. Here, we explore the genetic diversity of a desert lizard that occupies a wide range of environmental conditions and that has experienced post-glacial expansion northwards along two colonization routes. Based on our analyses of a large SNP data set, we find evidence that both climate and demographic history have shaped the genetic structure of populations. Pronounced genetic differentiation was evident between populations occupying cold versus hot deserts, and we detected numerous loci with significant associations with climate. The genetic signal of founder effects, however, is still present in the genomes of the recently expanded populations, which comprise subsets of genetic variation found in the southern populations.