Long-Term Follow-Up of Intravitreal Ranibizumab for the Treatment of Choroidal Neovascularization due to Choroidal Osteoma

Choroidal osteoma is an uncommon benign osseous intraocular tumor that typically affects young adult women. Choroidal neovascularization (CNV) is one of the complications that can develop in eyes with choroidal osteoma. We present a case of CNV secondary to choroidal osteoma treated with intravitreal ranibizumab. A 57-year-old lady presented with painless loss of vision with a right-eye visual acuity of 20/800. Fundus examination showed a well-demarcated yellowish peripapillary choroidal osteoma with associated retinal and subretinal hemorrhage due to CNV. Three intravitreal ranibizumab injections at monthly intervals were given and her visual acuity improved to 20/30 following treatment. After 1.2 years of follow-up, the right eye visual acuity was maintained at 20/30 with no evidence of CNV recurrence. Our findings suggest that intravitreal ranibizumab may be an effective therapeutic option for treating CNV secondary to choroidal osteoma

Neutrino mass in cosmology: status and prospects

I give an overview of the effects of neutrino masses in cosmology, focussing on the role they play in the evolution of cosmological perturbations. I discuss how recent observations of the cosmic microwave background anisotropies and the large-scale matter distribution can probe neutrino masses with greater precision than current laboratory experiments. I describe several new techniques that will be used to probe cosmology in the future, as well as recent advances in the computation of the nonlinear matter power spectrum and related observables.Comment: 41 pages, 5 figures, written for the Annual Review of Nuclear and Particle Science in January 2011. Publisher limits the number of references. Apologies if I missed your

Determinants of antibiotic prescribing for upper respiratory tract infections in an emergency department with good primary care access: a qualitative analysis

Upper respiratory tract infections (URTIs) account for substantial attendances at emergency departments (EDs). There is a need to elucidate determinants of antibiotic prescribing in time-strapped EDs – popular choices for primary care despite highly accessible primary care clinics. Semi-structured in-depth interviews were conducted with purposively sampled physicians (n = 9) in an adult ED in Singapore. All interviews were analysed using thematic analysis and further interpreted using the Social Ecological Model to explain prescribing determinants. Themes included: (1) reliance on clinical knowledge and judgement, (2) patient-related factors, (3) patient–physician relationship factors, (4) perceived practice norms, (5) policies and treatment guidelines and (6) patient education and awareness. The physicians relied strongly on their clinical knowledge and judgement in managing URTI cases and seldom interfered with their peers’ clinical decisions. Despite departmental norms of not prescribing antibiotics for URTIs, physicians would prescribe antibiotics when faced with uncertainty in patients’ diagnoses, treating immunocompromised or older patients with comorbidities, and for patients demanding antibiotics, especially under time constraints. Participants had a preference for antibiotic prescribing guidelines based on local epidemiology, but viewed hospital policies on prescribing as a hindrance to clinical judgement. Participants highlighted the need for more public education and awareness on the appropriate use of antibiotics and management of URTIs. Organisational practice norms strongly influenced antibiotic prescribing decisions by physicians, who can be swayed by time pressures and patient demands. Clinical decision support tools, hospital guidelines and patient education targeting at individual, interpersonal and community levels could reduce unnecessary antibiotic use

Interacting neutrinos in cosmology: exact description and constraints

We consider the impact of neutrino self-interactions described by an effective four-fermion coupling on cosmological observations. Implementing the exact Boltzmann hierarchy for interacting neutrinos first derived in [arxiv:1409.1577] into the Boltzmann solver CLASS, we perform a detailed numerical analysis of the effects of the interaction on the cosmic microwave background (CMB) anisotropies, and compare our results with known approximations in the literature. While we find good agreement between our exact approach and the relaxation time approximation used in some recent studies, the popular $\left( c_{\text{eff}}^2,c_{\text{vis}}^2 \right)$-parameterisation fails to reproduce the correct scale dependence of the CMB temperature power spectrum. We then proceed to derive constraints on the effective coupling constant $G_{\text{eff}}$ using currently available cosmological data via an MCMC analysis. Interestingly, our results reveal a bimodal posterior distribution, where one mode represents the standard $\Lambda$CDM limit with $G_{\rm eff} \lesssim 10^8 \, G_{\rm F}$, and the other a scenario in which neutrinos self-interact with an effective coupling constant $G_{\rm eff} \simeq 3 \times 10^9 \, G_{\rm F}$.Comment: 25 pages, 11 figures; accepted for publication in JCA

Optical activity of neutrinos and antineutrinos

Using the one-loop helicity amplitudes for low-energy $\nu\gamma\to\nu\gamma$ and $\bar\nu\gamma\to\bar\nu\gamma$ scattering in the standard model with massless neutrinos, we study the optical activity of a sea of neutrinos and antineutrinos. In particular, we estimate the values of the index of refraction and rotary power of this medium in the absence of dispersion.Comment: Additional reference

Neutrinos in Non-linear Structure Formation - a Simple SPH Approach

We present a novel method for implementing massive neutrinos in N-body simulations. Instead of sampling the neutrino velocity distribution by individual point particles we take neutrino free-streaming into account by treating it as an effective redshift dependent sound speed in a perfect isothermal fluid, and assume a relation between the sound speed and velocity dispersion of the neutrinos. Although the method fails to accurately model the true neutrino power spectrum, it is able to calculate the total matter power spectrum to the same accuracy as more complex hybrid neutrino methods, except on very small scales. We also present an easy way to update the publicly available Gadget-2 version with this neutrino approximation.Comment: 13 pages, 7 figure

Neutrino and axion hot dark matter bounds after WMAP-7

We update cosmological hot dark matter constraints on neutrinos and hadronic axions. Our most restrictive limits use 7-year data from the Wilkinson Microwave Anisotropy Probe for the cosmic microwave background anisotropies, the halo power spectrum (HPS) from the 7th data release of the Sloan Digital Sky Survey, and the Hubble constant from Hubble Space Telescope observations. We find 95% C.L. upper limits of \sum m_\nu<0.44 eV (no axions), m_a<0.91 eV (assuming \sum m_\nu=0), and \sum m_\nu<0.41 eV and m_a<0.72 eV for two hot dark matter components after marginalising over the respective other mass. CMB data alone yield \sum m_\nu<1.19 eV (no axions), while for axions the HPS is crucial for deriving m_a constraints. This difference can be traced to the fact that for a given hot dark matter fraction axions are much more massive than neutrinos.Comment: 9 pages, 3 figures, uses iopart.cls; v2: one additional figure, references added, version accepted by JCA

RELA governs a network of islet-specific metabolic genes necessary for beta cell function

Published online: 14 June 2023AIMS/HYPOTHESIS: NF-κB activation unites metabolic and inflammatory responses in many diseases yet less is known about the role that NF-κB plays in normal metabolism. In this study we investigated how RELA impacts the beta cell transcriptional landscape and provides network control over glucoregulation. METHODS: We generated novel mouse lines harbouring beta cell-specific deletion of either the Rela gene, encoding the canonical NF-κB transcription factor p65 (βp65KO mice), or the Ikbkg gene, encoding the NF-κB essential modulator NEMO (βNEMOKO mice), as well as βA20Tg mice that carry beta cell-specific and forced transgenic expression of the NF-κB-negative regulator gene Tnfaip3, which encodes the A20 protein. Mouse studies were complemented by bioinformatics analysis of human islet chromatin accessibility (assay for transposase-accessible chromatin with sequencing [ATAC-seq]), promoter capture Hi-C (pcHi-C) and p65 binding (chromatin immunoprecipitation-sequencing [ChIP-seq]) data to investigate genome-wide control of the human beta cell metabolic programme. RESULTS: Rela deficiency resulted in complete loss of stimulus-dependent inflammatory gene upregulation, consistent with its known role in governing inflammation. However, Rela deletion also rendered mice glucose intolerant because of functional loss of insulin secretion. Glucose intolerance was intrinsic to beta cells as βp65KO islets failed to secrete insulin ex vivo in response to a glucose challenge and were unable to restore metabolic control when transplanted into secondary chemical-induced hyperglycaemic recipients. Maintenance of glucose tolerance required Rela but was independent of classical NF-κB inflammatory cascades, as blocking NF-κB signalling in vivo by beta cell knockout of Ikbkg (NEMO), or beta cell overexpression of Tnfaip3 (A20), did not cause severe glucose intolerance. Thus, basal p65 activity has an essential and islet-intrinsic role in maintaining normal glucose homeostasis. Genome-wide bioinformatic mapping revealed the presence of p65 binding sites in the promoter regions of specific metabolic genes and in the majority of islet enhancer hubs (~70% of ~1300 hubs), which are responsible for shaping beta cell type-specific gene expression programmes. Indeed, the islet-specific metabolic genes Slc2a2, Capn9 and Pfkm identified within the large network of islet enhancer hub genes showed dysregulated expression in βp65KO islets. CONCLUSIONS/INTERPRETATION: These data demonstrate an unappreciated role for RELA as a regulator of islet-specific transcriptional programmes necessary for the maintenance of healthy glucose metabolism. These findings have clinical implications for the use of anti-inflammatories, which influence NF-κB activation and are associated with diabetes.Nathan W. Zammit, Ying Ying Wong, Stacey N. Walters, Joanna Warren, Simon C. Barry, Shane T. Gre

Three Level Thoracolumbar Spondylectomy for Recurrent Giant Cell Tumour of the Spine: A Case Report

Giant cell tumour (GCT) is a benign tumour but can be locally aggressive and with the potential to metastasise especially to the lungs. Successful treatments have been reported for long bone lesions; however, optimal surgical and medical treatment for spinal and sacral lesions are not well established. In treating spinal GCTs, the aim is to achieve complete tumour excision, restore spinal stability and decompress the neural tissues. The ideal surgical procedure is an en bloc spondylectomy or vertebrectomy, where all tumour cells are removed as recurrence is closely related to the extent of initial surgical excision. However, such a surgery has a high complication rate, such as dura tear and massive blood loss. We report a patient with a missed pathological fracture of T12 treated initially with a posterior subtraction osteotomy, who had recurrence three years after the index surgery and subsequently underwent a three level vertebrectomy and posterior spinal fusion