Accounting for Location Uncertainty in Azimuthal Telemetry Data Improves Ecological Inference

Background: Characterizing animal space use is critical for understanding ecological relationships. Animal telemetry technology has revolutionized the fields of ecology and conservation biology by providing high quality spatial data on animal movement. Radio-telemetry with very high frequency (VHF) radio signals continues to be a useful technology because of its low cost, miniaturization, and low battery requirements. Despite a number of statistical developments synthetically integrating animal location estimation and uncertainty with spatial process models using satellite telemetry data, we are unaware of similar developments for azimuthal telemetry data. As such, there are few statistical options to handle these unique data and no synthetic framework for modeling animal location uncertainty and accounting for it in ecological models. We developed a hierarchical modeling framework to provide robust animal location estimates from one or more intersecting or non-intersecting azimuths. We used our azimuthal telemetry model (ATM) to account for azimuthal uncertainty with covariates and propagate location uncertainty into spatial ecological models. We evaluate the ATM with commonly used estimators (Lenth (1981) maximum likelihood and M-Estimators) using simulation. We also provide illustrative empirical examples, demonstrating the impact of ignoring location uncertainty within home range and resource selection analyses. We further use simulation to better understand the relationship among location uncertainty, spatial covariate autocorrelation, and resource selection inference. Results: We found the ATM to have good performance in estimating locations and the only model that has appropriate measures of coverage. Ignoring animal location uncertainty when estimating resource selection or home ranges can have pernicious effects on ecological inference. Home range estimates can be overly confident and conservative when ignoring location uncertainty and resource selection coefficients can lead to incorrect inference and over confidence in the magnitude of selection. Furthermore, our simulation study clarified that incorporating location uncertainty helps reduce bias in resource selection coefficients across all levels of covariate spatial autocorrelation. Conclusion: The ATM can accommodate one or more azimuths when estimating animal locations, regardless of how they intersect; this ensures that all data collected are used for ecological inference. Our findings and model development have important implications for interpreting historical analyses using this type of data and the future design of radio-telemetry studies

The cyclical cascade of HIV care: Temporal care engagement trends within a population-wide cohort

Background: The traditional HIV treatment cascade aims to visualise the journey of each person living with HIV from diagnosis, through initiation on antiretroviral therapy (ART) to treatment success, represented by virological suppression. This representation has been a pivotal tool in highlighting and quantifying sequential gaps along the care continuum. There is longstanding recognition, however, that this may oversimplify the complexity of real-world engagement with HIV services in settings with mature high-burden HIV epidemics. A complementary “cyclical” cascade has been proposed to represent the processes of disengagement at different points on the care continuum, with multiple pathways to re-engagement, although the feasibility of implementing this at scale has been uncertain. This study aimed to populate, refine, and explore the utility of a cyclical representation of the HIV cascade, using routine data from a high-burden HIV setting. Methods and findings: This observational cohort study leveraged person-level data on all people living with HIV in the Western Cape (WC), South Africa, who accessed public health services in the 2 years prior to 31 December 2023. Programme data from disease registers were complemented by data from pharmacy and laboratory systems. At study closure, 494 370 people were included, constituting 93% of those of those estimated to be living with HIV in the province, of whom 355 104 were on ART. Substantial disengagement from HIV care was evident at every point on the cascade. Early treatment emerged as a period of higher risk of disengagement, but it did not account for the majority of disengagement. Almost all those currently disengaged had prior experience of treatment. While re-engagement was also common, overall treatment coverage had increased slowly over 5 years. The transition to dolutegravir-based regimens was dramatic with good virological outcomes for those in care, notwithstanding a clearly discernible impact of the Coronavirus Disease 2019 (COVID-19) pandemic on viral load (VL) testing. People currently engaged and disengaged in care are similar with respect to age and gender. Those who died or disengaged recently were previously distributed across a range of cascade statuses, and a substantial proportion of those newly initiating and re-initiating treatment were no longer on treatment 6 months later. The main limitation of this study was incomplete evidence of HIV testing, linkage to HIV-specific services, and out-of-facility mortality. Conclusions: Using routine data, it was possible to populate and automate a cyclical cascade of HIV care that continuously captured the nonlinear care journeys of individuals living with HIV. In this generalised mature HIV epidemic, most people are treatment experienced. Disengagement is common and occurs at various points along the cascade, making it challenging to identify high-impact intervention opportunities. While historical HIV cascades remain valuable for target setting and service monitoring, they can be complemented with insights from more detailed cyclical cascades

Population and antenatal-based HIV prevalence estimates in a high contracepting female population in rural South Africa.

BACKGROUND: To present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, we explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population. METHODS: HIV sero-prevalence amongst blood samples collected from women consenting to test during the 2005 annual longitudinal population-based serological survey was compared to anonymous unlinked HIV sero-prevalence amongst women attending antenatal care (ANC) first visits in six clinics (January to May 2005). Both surveillance systems were conducted as part of the Africa Centre Demographic Information System. RESULTS: Population-based HIV prevalence estimates for all women (25.2%) and pregnant women (23.7%) were significantly lower than that for ANC attendees (37.7%). A large proportion of women attending urban or peri-urban clinics would be predicted to be resident within rural areas. Although overall estimates remained significantly different, presenting and standardising estimates by age and location (clinic for ANC-based estimates and individual-residence for population-based estimates) made some group-specific estimates from the two surveillance systems more predictive of one another. CONCLUSION: It is likely that where ANC coverage and contraceptive use is widespread and fertility is low, population-based surveillance under-estimates HIV prevalence due to unrepresentative testing by age, residence and also probably by HIV status, and that ANC sentinel surveillance over-estimates prevalence due to selection bias in terms of age of sexual debut and contraceptive use. The results presented highlight the importance of accounting for unrepresentative testing, particularly by individual residence and age, through system design and statistical analyses

HIV incidence in men who have sex with men in England and Wales 2001-10: a nationwide population study.

BACKGROUND: Control of HIV transmission could be achievable through an expansion of HIV testing of at-risk populations together with ready access and adherence to antiretroviral therapy. To examine whether increases in testing rates and antiretroviral therapy coverage correspond to the control of HIV transmission, we estimated HIV incidence in men who have sex with men (MSM) in England and Wales since 2001. METHODS: A CD4-staged back-calculation model of HIV incidence was used to disentangle the competing contributions of time-varying rates of diagnosis and HIV incidence to observed HIV diagnoses. Estimated trends in time to diagnosis, incidence, and undiagnosed infection in MSM were interpreted against a backdrop of increased HIV testing rates and antiretroviral-therapy coverage over the period 2001-10. FINDINGS: The observed 3·7 fold expansion in HIV testing in MSM was mirrored by a decline in the estimated mean time-to-diagnosis interval from 4·0 years (95% credible interval [CrI] 3·8-4·2) in 2001 to 3·2 years (2·6-3·8) by the end of 2010. However, neither HIV incidence (2300-2500 annual infections) nor the number of undiagnosed HIV infections (7370, 95% CrI 6990-7800, in 2001, and 7690, 5460-10 580, in 2010) changed throughout the decade, despite an increase in antiretroviral uptake from 69% in 2001 to 80% in 2010. INTERPRETATION: CD4 cell counts at HIV diagnosis are fundamental to the production of robust estimates of incidence based on HIV diagnosis data. Improved frequency and targeting of HIV testing, as well as the introduction of ART at higher CD4 counts than is currently recommended, could begin a decline in HIV transmission among MSM in England and Wales. FUNDING: UK Medical Research Council, UK Health Protection Agency

Bridging Physics and Biology Teaching through Modeling

As the frontiers of biology become increasingly interdisciplinary, the physics education community has engaged in ongoing efforts to make physics classes more relevant to life sciences majors. These efforts are complicated by the many apparent differences between these fields, including the types of systems that each studies, the behavior of those systems, the kinds of measurements that each makes, and the role of mathematics in each field. Nonetheless, physics and biology are both sciences that rely on observations and measurements to construct models of the natural world. In the present theoretical article, we propose that efforts to bridge the teaching of these two disciplines must emphasize shared scientific practices, particularly scientific modeling. We define modeling using language common to both disciplines and highlight how an understanding of the modeling process can help reconcile apparent differences between the teaching of physics and biology. We elaborate how models can be used for explanatory, predictive, and functional purposes and present common models from each discipline demonstrating key modeling principles. By framing interdisciplinary teaching in the context of modeling, we aim to bridge physics and biology teaching and to equip students with modeling competencies applicable across any scientific discipline.Comment: 10 pages, 2 figures, 3 table

Blockade of Interferon Beta, but Not Interferon Alpha, Signaling Controls Persistent Viral Infection

SummaryAlthough type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNα and IFNβ are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNβ versus IFNα in controlling LCMV infection. While blockade of IFNβ alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNα was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNβ and IFNα have unique and distinguishable biologic functions, with IFNβ being mainly responsible for promoting viral persistence

Spatial Frequency Domain Tomography of Protoporphyrin IX Fluorescence in Preclinical Glioma Models

Multifrequency (0 to 0.3  mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼ 1.5 in reduced scattering coefficient for all wavelengths and was ∼ 1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors

Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on a steroid-regulated promoter

AbstractActivation of gene transcription involves chromatin remodeling by coactivator proteins that are recruited by DNA-bound transcription factors. Local modification of chromatin structure at specific gene promoters by ATP-dependent processes and by posttranslational modifications of histone N-terminal tails provides access to RNA polymerase II and its accompanying transcription initiation complex [1, 2]. While the roles of lysine acetylation, serine phosphorylation, and lysine methylation of histones in chromatin remodeling are beginning to emerge [2–5], low levels of arginine methylation of histones have only recently been documented [4, 6–9], and its physiological role is unknown. The coactivator CARM1 methylates histone H3 at Arg17 and Arg26 in vitro [7] and cooperates synergistically with p160-type coactivators (e.g., GRIP1, SRC-1, ACTR) and coactivators with histone acetyltransferase activity (e.g., p300, CBP) to enhance gene activation by steroid and nuclear hormone receptors (NR) in transient transfection assays [10, 11]. In the current study, CARM1 cooperated with GRIP1 to enhance steroid hormone-dependent activation of stably integrated mouse mammary tumor virus (MMTV) promoters, and this coactivator function required the methyltransferase activity of CARM1. Chromatin immunoprecipitation assays and immunofluorescence studies indicated that CARM1 and the CARM1-methylated form of histone H3 specifically associated with a large tandem array of MMTV promoters in a hormone-dependent manner. Thus, arginine-specific histone methylation by CARM1 is an important part of the transcriptional activation process

Nitric oxide precursors and congenital heart surgery: A randomized controlled trial of oral citrulline

ObjectiveThe study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension.Study DesignForty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline and arginine concentrations were measured at 5 time points. Measurements of systemic blood pressure and presence of pulmonary hypertension were collected.ResultsMedian citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately postoperatively (36 μmol/L vs 26 μmol/L, P = .012) and at 12 hours postoperatively (37 μmol/L vs 20 μmol/L, P = .015). Mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively (36 μmol/L vs 23 μmol/L, P = .037). Mean systemic blood pressure did not differ between groups (P = .53). Postoperative pulmonary hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of 20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline concentrations less than age-specific norms. Postoperative pulmonary hypertension did not develop in patients who demonstrated plasma citrulline concentrations in excess of 37 μmol/L (P = .036).ConclusionsOral citrulline supplementation safely increased plasma citrulline and arginine concentrations compared with placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation. Oral citrulline supplementation may be effective in reducing postoperative pulmonary hypertension