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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.

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

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]

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.

Reliable methods for detecting and analyzing gene expression are necessary tools for understanding development and investigating biological responses to genetic and environmental perturbation. With its fully sequenced genome, invariant cell lineage, transparent body, wiring diagram, detailed anatomy, and wide array of genetic tools, Caenorhabditis elegans is an exceptionally useful model organism for linking gene expression to cellular phenotypes. The development of new techniques in recent years has greatly expanded our ability to detect gene expression at high resolution. Here, we provide an overview of gene expression methods for C. elegans, including techniques for detecting transcripts and proteins in situ, bulk RNA sequencing of whole worms and specific tissues and cells, single-cell RNA sequencing, and high-throughput proteomics. We discuss important considerations for choosing among these techniques and provide an overview of publicly available online resources for gene expression data., Competing Interests: Conflicts of interest: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

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.)

Circadian rhythms are important for maintaining homeostasis, from regulating physiological activities (e.g., sleep-wake cycle and cognitive performance) to cellular processes (e.g., cell cycle and DNA damage repair). Melatonin is a key regulator of circadian rhythms and exerts control by binding to melatonin receptor 1 (MT1), decreasing neuronal firing in the suprachiasmatic nucleus (SCN). Previous work studying effects of melatonin on circadian rhythms utilized in vivo models. Since MT1 is also expressed outside of the brain, it is important to study impacts of melatonin on circadian gene oscillations in vitro. We evaluated the effects of melatonin and an MT1 inverse agonist, UCSF7447, in U2OS circadian reporter cell lines, which facilitate detailed assessments of oscillatory changes. We report that cellular circadian rhythms are responsive to treatment with MT1-targeting molecules; their activities are not dependent upon the SCN. Corroborating in vivo data, both melatonin and UCSF7447 lengthened the periods of BMAL1 and PER2 , and while melatonin delayed circadian phases, UCSF7447 advanced them. Compounds were also dosed at two different times, however this did not yield changes. Our findings indicate the importance of utilizing in vitro models and that the direct effects of melatonin likely go beyond the SCN and should be explored further.