Ventricular Entrapment Due To Isolated Intraventricular Aspergillus Infection

Introduction: Intraventricular aspergillus infections are a rare manifestation of fungal infections of the central nervous system (CNS). Intraventricular aspergillus infections have most commonly been identified in immunocompromised patients. Spread to the central nervous system is thought to occur hematogenously (usually from pulmonary infection) or directly from the paranasal sinuses. Clinical diagnosis is difficult, as symptoms are nonspecific, but imaging can be used to create a more accurate differential. This case report describes the rare diagnosis of an intraventricular aspergillus infection in an immunocompromised patient presenting with ventricular entrapment and demonstrates the role of imaging in making the diagnosis. Case Report: We present the case of a 59-year-old male with a history of renal transplant on immunosuppressive therapy, presenting with a two-week history of right-sided weakness and speech difficulty. Of note, patient was diagnosed with acute invasive pulmonary aspergillosis during a prior admission this year and had just completed a 12-week course of antifungal therapy. CT of the head at that time demonstrated only slight asymmetry of the ventricles without definite intracranial lesion. Initial non-contrast CT of the head demonstrated a complex cystic mass within the left lateral ventricle with asymmetric ventricular enlargement. CT of the head with contrast demonstrated a complex lesion within the left ventricle with peripheral enhancement and enlargement of the ventricle. MRI demonstrated a cystic lesion within the left lateral ventricle with a hyperintense FLAIR component anteriorly with restricted diffusion. Post-contrast MRI showed enhancement at the periphery of the complex lesion. There was also entrapment of the left lateral ventricle. After placement of an external ventricular drain for hydrocephalus, surgical biopsy of the lesion demonstrated numerous uniform, septate, fungal hyphae with rare acute angle branching consistent with aspergillus. Throughout the admission, there had been slow, but progressive, decline in neurological function. The patient has been continued on antifungal therapy pending improvement in neurological function. Conclusion: Isolated intraventricular aspergillus infection is a rare manifestation of CNS fungal infection, most commonly seen in immunocompromised patients. Given the nonspecific clinical symptoms of this diagnosis, imaging can localize and narrow the vast differential for these CNS lesions. Patients that have been diagnosed as such require immediate, long-term, and systemic antifungal therapy. With the mortality rate of patients with intraventricular aspergillus infections being highly dependent on accurate and immediate diagnosis, recognizing key imaging features can aid in improving current poor outcomes.https://scholarlycommons.henryford.com/merf2020caserpt/1097/thumbnail.jp

Crystallization of Bosonic Quantum Hall States

The dominance of interactions over kinetic energy lies at the heart of strongly correlated quantum matter, from fractional quantum Hall liquids, to atoms in optical lattices and twisted bilayer graphene. Crystalline phases often compete with correlated quantum liquids, and transitions between them occur when the energy cost of forming a density wave approaches zero. A prime example occurs for electrons in high magnetic fields, where the instability of quantum Hall liquids towards a Wigner crystal is heralded by a roton-like softening of density modulations at the magnetic length. Remarkably, interacting bosons in a gauge field are also expected to form analogous liquid and crystalline states. However, combining interactions with strong synthetic magnetic fields has been a challenge for experiments on bosonic quantum gases. Here, we study the purely interaction-driven dynamics of a Landau gauge Bose-Einstein condensate in and near the lowest Landau level (LLL). We observe a spontaneous crystallization driven by condensation of magneto-rotons, excitations visible as density modulations at the magnetic length. Increasing the cloud density smoothly connects this behaviour to a quantum version of the Kelvin-Helmholtz hydrodynamic instability, driven by the sheared internal flow profile of the rapidly rotating condensate. At long times the condensate self-organizes into a persistent array of droplets, separated by vortex streets, which are stabilized by a balance of interactions and effective magnetic forces

Geometric squeezing into the lowest Landau level

The equivalence between neutral particles under rotation and charged particles in a magnetic field relates phenomena as diverse as spinning atomic nuclei, weather patterns, and the quantum Hall effect. In their quantum descriptions, translations along different directions do not commute, implying a Heisenberg uncertainty relation between spatial coordinates. Here, we exploit the ability to squeeze non-commuting variables to dynamically create a Bose-Einstein condensate occupying a single Landau gauge wavefunction in the lowest Landau level. We directly resolve the extent of the zero-point cyclotron orbits, and demonstrate geometric squeezing of the orbits' guiding centers by more than ${7}~$dB below the standard quantum limit. The condensate attains an angular momentum of more than ${1000}\,{\hbar}$ per particle, and an interatomic distance comparable to the size of the cyclotron orbits. This offers a new route towards strongly correlated fluids and bosonic quantum Hall states.Comment: 6 pages, 4 figures and Supplementary Materials of 8 pages, 4 figure

Inequalities in access to paid sick leave among workers in England and Wales

Background: It is poorly understood which workers lack access to sick pay in England and Wales. This evidence gap has been of particular interest in the context of the Covid-19 pandemic given the relationship between presenteeism and infectious disease transmission. // Method: This cross-sectional analysis (n = 8874) was nested within a large community cohort study based across England and Wales (Virus Watch). An online survey in February 2021 asked participants in work if they had access to paid sick leave. We used logistic regression to examine sociodemographic factors associated with lacking access to sick pay. // Results: Only 66% (n = 5864) of participants reported access to sick pay. South Asian workers (adjusted odds ratio [OR] 1.40, 95% confidence interval [CI] 1.06–1.83) and those from Other minority ethnic backgrounds (OR 2.93, 95% CI 1.54–5.59) were more likely to lack access to sick pay compared to White British workers. Older workers (OR range 1.72 [1.53–1.93]–5.26 [4.42–6.26]), workers in low-income households (OR 2.53, 95% CI 2.15–2.98) and those in transport, trade, and service occupations (OR range 2.03 [1.58–2.61]–5.29 [3.67–7.72]) were also more likely to lack access to sick pay compared respectively to workers aged 25–44, those in high income households and managerial occupations. // Discussion: Unwarranted age and ethnic inequalities in sick pay access are suggestive of labour market discrimination. Occupational differences are also cause for concern. Policymakers should consider expanding access to sick pay to mitigate transmission of Covid-19 and other endemic respiratory infections in the community, and in the context of pandemic preparation

BALR-6 regulates cell growth and cell survival in B-lymphoblastic leukemia

BackgroundA new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), has been recently described. These lncRNAs are implicated to play pivotal roles in various molecular processes, including development and oncogenesis. Gene expression profiling of human B-ALL samples showed differential lncRNA expression in samples with particular cytogenetic abnormalities. One of the most promising lncRNAs identified, designated B-ALL associated long RNA-6 (BALR-6), had the highest expression in patient samples carrying the MLL rearrangement, and is the focus of this study.ResultsHere, we performed a series of experiments to define the function of BALR-6, including several novel splice forms that we identified. Functionally, siRNA-mediated knockdown of BALR-6 in human B-ALL cell lines caused reduced cell proliferation and increased cell death. Conversely, overexpression of BALR-6 isoforms in both human and mouse cell lines caused increased proliferation and decreased apoptosis. Overexpression of BALR-6 in murine bone marrow transplantation experiments caused a significant increase in early hematopoietic progenitor populations, suggesting that its dysregulation may cause developmental changes. Notably, the knockdown of BALR-6 resulted in global dysregulation of gene expression. The gene set was enriched for leukemia-associated genes, as well as for the transcriptome regulated by Specificity Protein 1 (SP1). We confirmed changes in the expression of SP1, as well as its known interactor and downstream target CREB1. Luciferase reporter assays demonstrated an enhancement of SP1-mediated transcription in the presence of BALR-6. These data provide a putative mechanism for regulation by BALR-6 in B-ALL.ConclusionsOur findings support a role for the novel lncRNA BALR-6 in promoting cell survival in B-ALL. Furthermore, this lncRNA influences gene expression in B-ALL in a manner consistent with a function in transcriptional regulation. Specifically, our findings suggest that BALR-6 expression regulates the transcriptome downstream of SP1, and that this may underlie the function of BALR-6 in B-ALL

Nucleocapsid and spike antibody responses post virologically confirmed SARS-CoV-2 infection: An observational analysis in the Virus Watch community cohort

Objectives: Seroprevalence studies can provide a measure of SARS-CoV-2 cumulative incidence, but a better understanding of spike (anti-S) and nucleocapsid (anti-N) antibody dynamics following infection is needed to assess longevity of detectability. / Methods: Adults aged ≥18 years old, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary-blood samples which were tested for anti-S and anti-N. Participants self-reported vaccination dates and past medical history. Prior polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System (SGSS) linkage data. Primary outcome variables were seropositivity and total anti-N and anti-S levels after PCR confirmed infection. / Results: A total of 13,802 eligible individuals provided 58,770 capillary blood samples. 537 of these had a prior positive PCR confirmed SARS-CoV-2 infection within 0-269 days of antibody sample date, with 432 (80.45%) having a positive anti-N result. Median anti-N levels peaked between days 90 and 119 post PCR results and then began to decline. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories. / Conclusion: Our findings suggests that anti-N have around 80% sensitivity for identifying previous COVID-19 infection and duration of detectability is affected by sex and age

Reported exposure to SARS-CoV-2 and relative perceived importance of different settings for SARS-CoV-2 acquisition in England and Wales: Analysis of the Virus Watch Community Cohort

We aimed to assess the relative importance of different settings for SARS-CoV-2 transmission in a large community cohort based on perceived location of infection for self-reported confirmed SARS-COV-2 cases. We demonstrate the importance of home, work and education as perceived venues for transmission. In children, education was most important and in older adults essential shopping was of high importance.  Our findings support public health messaging about infection control at home, advice on working from home and restrictions in different venues.</ns3:p

Comparative effectiveness of different primary vaccination courses on mRNA-based booster vaccines against SARs-COV-2 infections: a time-varying cohort analysis using trial emulation in the Virus Watch community cohort.

BACKGROUND: The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK's booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual's primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations. METHODS: Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driven by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation. RESULTS: A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13. CONCLUSION: After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection

Nucleocapsid and spike antibody responses following virologically confirmed SARS-CoV-2 infection: an observational analysis in the Virus Watch community cohort.

OBJECTIVES: Seroprevalence studies can provide a measure of SARS-CoV-2 cumulative incidence, but a better understanding of spike and nucleocapsid (anti-N) antibody dynamics following infection is needed to assess the longevity of detectability. METHODS: Adults aged ≥18 years, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples, which were tested for spike antibody and anti-N. Participants self-reported vaccination dates and past medical history. Previous polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System linkage data. The primary outcome variables were seropositivity and total anti-N and spike antibody levels after PCR-confirmed infection. RESULTS: A total of 13,802 eligible individuals provided 58,770 capillary blood samples. A total of 537 of these had a previous positive PCR-confirmed SARS-CoV-2 infection within 0-269 days of antibody sample date, among them 432 (80.45%) having a positive anti-N result. Median anti-N levels peaked between days 90 and 119 after PCR results and then began to decline. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories. CONCLUSION: Our findings suggest that anti-N has around 80% sensitivity for identifying previous COVID-19 infection, and the duration of detectability is affected by sex and age