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Lavnish Joshi,1–3 Asaf Bar,4 Oren Tomkins-Netzer,1,3 Satish Yaganti,1 Jiten Morarji,1 Panayiotis Vouzounis,1 Sophie Seguin-Greenstein,1,4 Simon R Taylor,3,5 Sue Lightman1,3 1Department of Clinical Ophthalmology, UCL Institute of Ophthalmology and Moorfields Eye Hospital, London, UK; 2Ophthalmology Department, Ashford & St Peter’s NHS Foundation Trust, Ashford, Middlesex, UK; 3Ophthalmology Department, Royal Surrey County Hospital NHS Foundation Trust, Guildford, Surrey, UK; 4Ophthalmology Department, Wolfson Medical Center, Holon Israel; 5Ophthalmology Department, University of Surrey, Guildford, Surrey, UK Background: Outcomes of intravitreal antivascular endothelial growth factor injections are variable among patients with diabetic macular edema (DME). The aim of this study was to determine the ocular and systemic predictors of DME response to intravitreal bevacizumab (IVB). Methods: Retrospective review over 2 years of 78 eyes from 54 patients. An anatomical response to IVB was defined as a 20% reduction in central macula thickness after the first course (three injections) of IVB. Results: Twenty-eight percent of patients had an anatomical response after the first course of IVB. Systemic hypertension (odds ratio, 95% confidence interval: 12.1, 0.7–21) was a statistically significant predictor (P=0.025) of a good response to IVB, whereas previous macular laser was a statistically significant (P=0.0005) predictor of a poor response (0.07, 0.01–0.32). Sixty-eight percent of eyes underwent subsequent treatment for DME after the first course of IVB. The visual acuity gain at 24 months in hypertensive (0.7±3.6 letters) and nonhypertensive (5.2±3.7 letters) patients was not significantly different (P=0.41). Conclusion: Hypertension and previous macular laser were positive and negative predictors of response to IVB, respectively. However, long-term visual acuity changes were not significantly different between eyes with and without systemic hypertension. Keywords: diabetes, macular edema, intravitreal therapy

We have constructed a new time-scale, TT(IPTA16), based on observations of radio pulsars presented in the first data release from the International Pulsar Timing Array (IPTA). We used two analysis techniques with independent estimates of the noise models for the pulsar observations and different algorithms for obtaining the pulsar time-scale. The two analyses agree within the estimated uncertainties and both agree with TT(BIPM17), a post-corrected time-scale produced by the Bureau International des Poids et Mesures (BIPM). We show that both methods could detect significant errors in TT(BIPM17) if they were present. We estimate the stability of the atomic clocks from which TT(BIPM17) is derived using observations of four rubidium fountain clocks at the US Naval Observatory. Comparing the power spectrum of TT(IPTA16) with that of these fountain clocks suggests that pulsar-based time-scales are unlikely to contribute to the stability of the best time-scales over the next decade, but they will remain a valuable independent check on atomic time-scales. We also find that the stability of the pulsar-based time-scale is likely to be limited by our knowledge of solar-system dynamics, and that errors in TT(BIPM17) will not be a limiting factor for the primary goal of the IPTA, which is to search for the signatures of nano-Hertz gravitational waves.

We analyse the stochastic properties of the 49 pulsars that comprise the first International Pulsar Timing Array (IPTA) data release. We use Bayesian methodology, performing model selection to determine the optimal description of the stochastic signals present in each pulsar. In addition to spin-noise and dispersion-measure (DM) variations, these models can include timing noise unique to a single observing system, or frequency band. We show the improved radio-frequency coverage and presence of overlapping data from different observing systems in the IPTA data set enables us to separate both system and band-dependent effects with much greater efficacy than in the individual pulsar timing array (PTA) data sets. For example, we show that PSR J1643-1224 has, in addition to DM variations, significant band-dependent noise that is coherent between PTAs which we interpret as coming from time-variable scattering or refraction in the ionized interstellar medium. Failing to model these different contributions appropriately can dramatically alter the astrophysical interpretation of the stochastic signals observed in the residuals. In some cases, the spectral exponent of the spin-noise signal can vary from 1.6 to 4 depending upon the model, which has direct implications for the long-term sensitivity of the pulsar to a stochastic gravitational-wave (GW) background. By using a more appropriate model, however, we can greatly improve a pulsar's sensitivity to GWs. For example, including system and band-dependent signals in the PSR J0437-4715 data set improves the upper limit on a fiducial GW background by ~60 per cent compared to a model that includes DM variations and spin-noise only.

Objectives: To determine whether weight problems in children (overweight, obesity and overweight or obesity) were related to deprivation indices when attributed only according to electoral ward of the school attended. To determine whether children with weight problems were more likely to be found in some wards rather than others, and to compare the distribution for boys and girls.Design: Retrospective, cross-sectional, observational study.Setting: One hundred and six primary schools from all parts of Liverpool city.Subjects: Five cohorts of 9-10-year-old children between 1998 and 2003.Main Outcome Measures: Body mass index (BMI) for each child to estimate proportions overweight, obese and overweight or obese according to international criteria.Results: Between January 1998 and March 2003, the heights and weights of 7902 boys and 7514 girls were measured and BMI calculated. The prevalence of boys and girls categorised as overweight or obese was very high (1620, 20.6% and 1909, 25.7%, respectively). Prevalence was not related to deprivation and varied between wards only for the girls; some wards had very different prevalence rates for boys and girls (Picton: 59 boys, 23.4%; 106 girls, 36.6%). The most deprived ward did not have a remarkable prevalence of overweight or obesity (Speke: 32 boys, 15.3%; 40 girls, 19.8%).Conclusions: Obesity is a major problem and requires urgent action but targeting intervention on the basis of administrative areas may be very wasteful. Different factors seem to lead to obesity in boys and girls, and attention should be paid to the role of the physical environment. [ABSTRACT FROM AUTHOR]

Victor Menezo,1,2 Simon RJ Taylor3,4 1Institut Catala de Retina, Barcelona, Spain; 2Department of Ophthalmology, Provincial Hospital Consortium Castellon, Castello, Spain; 3Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK; 4Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK Abstract: Birdshot chorioretinopathy is a relatively uncommon subtype of idiopathic posterior uveitis with distinct clinical characteristics and a strong genetic association with the Human Leukocyte Antigen (HLA)-A29 allele. The diagnosis remains clinical and is based on the presence of typical clinical features, including multiple, distinctive, hypopigmented choroidal lesions throughout the fundus. The long-term visual prognosis of this disorder, however, remains guarded – central visual acuity can be preserved until late in the disease and it is not uncommon for patients to receive inadequate immunosuppressive treatment, leading to a poor long-term outcome in which peripheral retinal damage eventually leads to visual deterioration. Birdshot chorioretinopathy has proven a particularly attractive area of study within the field of uveitis, as it is a relatively easily defined disease with an associated human leukocyte antigen haplotype. Despite this, however, the immune mechanisms involved in its pathogenesis remain unclear, and some patients continue to lose retinal function despite therapy with corticosteroids and conventional immunosuppressive agents. Laboratory research continues to investigate the underlying mechanisms of disease, and clinical research is now being driven to improve the phenotyping and monitoring of this condition as, in the era of so-called personalized medicine, it is becoming increasingly important to identify patients at risk of visual loss early so that they can be treated more aggressively with targeted therapies such as the newer biological agents. This approach requires the formation of collaborative groups, as the relative rarity of the condition makes it difficult for one center to accumulate enough patients for worthwhile studies. Nevertheless, results obtained with newer therapies, such as biological agents directed against particular cytokines or cell-surface receptors, demonstrate ever improving control of the inflammation in refractory cases, providing hope that the outlook for visual function in this condition can only improve. Keywords: birdshot chorioretinopathy, HLA-A29, retinal vasculitis, Th17 cells, monoclonal antibodies, interleukin antagonists

Discusses the abstract of the articles `What's Intermediate About `Intermediate' Sanctions? The Case of Young Offender Dispositions in Canada,' by Voula Marinos and `The Dangerous Offender Provisions; Are They Targeting the Right Offenders?,' by James Bonta, Ivan Zinger et al, published in the `Canadian Journal of Criminology,' dated October 1998.

Discusses the article titled `Rethinking Community Resistance to Prison Siting: Results From a Community Impact Assessment,' by Michael Young, which appeared in the July 1998 issue of `Canadian Journal of Criminology.' Public support for penal institutions in Canada; `Not in my backyard' syndrome.

Discusses the topics featured in the article "Mandatory Minimum Sentences: A Utilitarian Perspective," by Thomas Gabor in the July 2001 issue of the "Canadian Journal of Criminology." Increase in the promulgation of minimum sentences in Canada and the U.S.; Criticisms commonly leveled against mandatory sentences; Anecdotes demonstrating disproportionate sentences.

Adenosine-to-inosine (A-to-I) editing of double-stranded RNA (dsRNA) by ADAR1 is an essential modifier of the immunogenicity of cellular dsRNA. The role of MDA5 in sensing unedited cellular dsRNA and the downstream activation of type I interferon (IFN) signaling are well established. However, we have an incomplete understanding of pathways that modify the response to unedited dsRNA. We performed a genome-wide CRISPR screen and showed that GGNBP2, CNOT10, and CNOT11 interact and regulate sensing of unedited cellular dsRNA. We found that GGNBP2 acts between dsRNA transcription and its cytoplasmic sensing by MDA5. GGNBP2 loss prevented induction of type I IFN and autoinflammation after the loss of ADAR1 editing activity by modifying the subcellular distribution of endogenous A-to-I editing substrates and reducing cytoplasmic dsRNA load. These findings reveal previously undescribed pathways to modify diseases associated with ADAR mutations and may be determinants of response or resistance to small-molecule ADAR1 inhibitors.

The C. elegans nervous system is compact and well described, ideal for identifying genetic programs that drive neuron-specific development, function, and connectivity. Here, we present a protocol for isolating specific neuron types for gene expression profiling by bulk or single-cell RNA sequencing. We describe steps for worm synchronization, dissociation, and fluorescence-activated cell sorting (FACS) isolation. We then detail procedures for RNA extraction and preparing cells for single-cell sequencing. This protocol is applicable to the isolation of individual cell types from larval and adult animals. For additional details on the use and execution of this protocol, see Taylor et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)