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Abstract Background Identifying successful strategies to improve participant retention in longitudinal studies remains a challenge. In this study we evaluated whether non-traditional fieldworker shifts (after hours during the week and weekends) enhanced participant retention when compared to retention during traditional weekday shifts in the HPTN 071 (PopART) population cohort (PC). Methods HPTN 071 (PopART) PC participants were recruited and followed up in their homes on an annual basis by research fieldworkers over a 3-4 year period. The average number of successful follow-up visits, where a PC participant was found and retained in the study, was calculated for each of 3 visit schedules (early weekday shift, late weekday shift, and Saturday shift), and standardized to account for variation in fieldwork shift duration. We used one-way univariate analysis of variance (ANOVA) to describe differences in mean-successful visits and 95% confidence intervals between the shift types. Results Data on 16 651 successful visits were included. Successful visit rates were higher when conducting Saturday visits (14.0; 95% CI: 11.3-16.6) compared to both regular (4.5; 95% CI: 3.7-5.3) and late weekday shifts (5.3; 95% CI: 4.7-5.8) overall and in all subgroup analyses (P

Abstract Background Reproductive containment provides an opportunity to implement a staged-release strategy for genetic control of malaria vectors, in particular allowing predictions about the spread and persistence of (self-limiting) sterile and male-biased strains to be compared to outcomes before moving to (self-sustaining) gene-drive strains. Methods In this study, we: (i) describe a diffusion–advection–reaction model of the spread and persistence of a single cohort of male mosquitoes; (ii) elicit informative prior distributions for model parameters, for wild-type (WT) and genetically modified dominant sterile strains (DSM); (iii) estimate posterior distributions for WT strains using data from published mark-recapture-release (MRR) experiments, with inference performed through the Delayed-Rejection Adaptive Metropolis algorithm; and (iv) weight prior distributions, in order to make predictions about genetically modified strains using Bayes factors calculated for the WT strains. Results If a single cohort of 5000 genetically modified dominant sterile male mosquitoes are released at the same location as previous MRR experiments with their WT counterparts, there is a 90% probability that the expected number of released mosquitoes will fall to < 1 in 10 days, and that by 12 days there will be a 99% probability that no mosquitoes will be found more than 150 m from the release location. Conclusions Spread and persistence models should form a key component of risk assessments of novel genetic control strategies for malaria vectors. Our predictions, used in an independent risk assessment, suggest that genetically modified sterile male mosquitoes will remain within the locality of the release site, and that they will persist for a very limited amount of time. Data gathered following the release of these mosquitoes will enable us to test the accuracy of these predictions and also provide a means to update parameter distributions for genetic strains in a coherent (Bayesian) framework. We anticipate this will provide additional insights about how to conduct probabilistic risk assessments of stage-released genetically modified mosquitoes. Graphical abstract

Abstract Recent advances in gene‐editing technologies have opened new avenues for genetic pest control strategies, in particular around the use of gene drives to suppress or modify pest populations. Significant uncertainty, however, surrounds the applicability of these strategies to novel target species, their efficacy in natural populations and their eventual safety and acceptability as control methods. In this article, we identify issues associated with the potential use of gene drives in agricultural systems, to control pests and diseases that impose a significant cost to agriculture around the world. We first review the need for innovative approaches and provide an overview of the most relevant biological and ecological traits of agricultural pests that could impact the outcome of gene drive approaches. We then describe the specific challenges associated with using gene drives in agricultural systems, as well as the opportunities that these environments may offer, focusing in particular on the advantages of high‐threshold gene drives. Overall, we aim to provide a comprehensive view of the potential opportunities and the remaining uncertainties around the use of gene drives in agricultural systems.

Abstract Deep saliency models represent the current state-of-the-art for predicting where humans look in real-world scenes. However, for deep saliency models to inform cognitive theories of attention, we need to know how deep saliency models prioritize different scene features to predict where people look. Here we open the black box of three prominent deep saliency models (MSI-Net, DeepGaze II, and SAM-ResNet) using an approach that models the association between attention, deep saliency model output, and low-, mid-, and high-level scene features. Specifically, we measured the association between each deep saliency model and low-level image saliency, mid-level contour symmetry and junctions, and high-level meaning by applying a mixed effects modeling approach to a large eye movement dataset. We found that all three deep saliency models were most strongly associated with high-level and low-level features, but exhibited qualitatively different feature weightings and interaction patterns. These findings suggest that prominent deep saliency models are primarily learning image features associated with high-level scene meaning and low-level image saliency and highlight the importance of moving beyond simply benchmarking performance.

Hexanucleotide repeat expansion in the intron 1 of the C9ORF72 gene can cause amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). Here the authors use single molecule imaging to show nuclear export and translation of circular repeat-containing C9ORF72 intronic RNA.

Introduction Ethnic disparities in treatment with clozapine, the antipsychotic recommended for treatment-resistant schizophrenia (TRS), have been reported. However, these investigations frequently suffer from potential residual confounding. For example, few studies have restricted the analyses to TRS samples and none has controlled for benign ethnic neutropenia. Objectives This study investigated if service-users’ ethnicity influenced clozapine prescription in a cohort of people with TRS. Methods Information from the clinical records of South London and Maudsley NHS Trust was used to identify a cohort of service-users with TRS between 2007 and 2017. In this cohort, we used logistic regression to investigate any association between ethnicity and clozapine prescription while adjusting for potential confounding variables, including sociodemographic factors, psychiatric multimorbidity, substance use, benign ethnic neutropenia, and inpatient and outpatient care received. Results We identified 2239 cases that met the criteria for TRS. Results show that after adjusting for confounding variables, people with Black African ethnicity had half the odds of being treated with clozapine and people with Black Caribbean or Other Black background had about two-thirds the odds of being treated with clozapine compared White British service-users. No disparities were observed regarding other ethnic groups, namely Other White background, South Asian, Other Asian, or any other ethnicity. Conclusions There was evidence of inequities in care among Black ethnic groups with TRS. Interventions targeting barriers in access to healthcare are recommended. Disclosure During the conduction of the study, DFdF, GKS, and RH received funds from the NIHR Maudsley Biomedical Research Centre. For other activities outside the submitted work, DFdF received research funding from the UK Department of Health and Social Care, Janss

Introduction Studies have shown ethnic inequalities in health, with a higher incidence of illnesses among people of some minoritised ethnic groups. Furthermore, it has been observed that people with severe mental illnesses have a higher risk for multimorbidity. However, no study has investigated ethnic disparities in comorbidity in people with a schizophrenia spectrum disorder. Objectives This study investigates potential ethnic disparities in physical health comorbidity in a cohort of people with psychosis. Methods Using a cross-sectional design, we identified service-users of the South London and Maudsley NHS Trust who were diagnosed with a schizophrenia spectrum disorder between 2007 and 2020. We assessed the prevalence of asthma, bronchitis, diabetes, hypertension, low blood pressure, overweight or obesity, and rheumatoid arthritis. Latent class analyses were used to investigate distinct profiles of comorbidity. Multinomial regression was then used to investigate ethnic disparities in these profiles. The regression model was adjusted for gender, age, neighbourhood deprivation, smoking and duration of care. Results On a sample of 23,418 service-users with psychosis, we identified two classes of comorbidity: low comorbidity and multiple comorbidities. Compared to the White British ethnicity, a higher risk for multiple comorbidities was observed for people with any Black background, Indian, Pakistani, Asian British, and mixed-race ethnicities. Furthermore, Black African women had a significantly higher risk for multiple comorbidities than their male counterparts. Conclusions Ethnic disparities are observed in multiple comorbidities among people with psychosis. Further research is needed to understand the impact of these disparities, especially in relation to mortality. Disclosure No significant relationships.

Introduction There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS. Objectives This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS. Methods Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. Results We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS. Conclusions Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance. Disclosure DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp

PurposeTo examine the time course of recovery for gait and neuromuscular function immediately after and 24-h post interval training. In addition, this study compared the impact of different statistical approaches on detecting changes.MethodsTwenty (10F, 10M) healthy, recreational club runners performed a high-intensity interval training (HIIT) session consisting of six repetitions of 800 m. A 6-min medium intensity run was performed pre, post, and 24-h post HIIT to assess hip and knee kinematics and coordination variability. Voluntary activation and twitch force of the quadriceps, along with maximum isometric force were examined pre, post, and 24-h post significance HIIT. The time course of changes were examined using two different statistical approaches: traditional null hypothesis significance tests and “real” changes using minimum detectable change.ResultsImmediately following the run, there were significant (P < 0.05) increases in the hip frontal kinematics and coordination variability. The runners also experienced a loss of muscular strength and neuromuscular function immediately post HIIT (P < 0.05). Individual assessment, however, showed that not all runners experienced fatigue effects immediately post HIIT. Null hypothesis significance testing revealed a lack of recovery in hip frontal kinematics, coordination variability, muscle strength, and neuromuscular function at 24-h post, however, the use of minimum detectable change suggested that most runners had recovered.ConclusionHigh intensity interval training resulted in altered running kinematics along with central and peripheral decrements in neuromuscular function. Most runners had recovered within 24-h, although a minority still exhibited signs of fatigue. The runners that were not able to recover prior to their run at 24-h were identified to be at an increased risk of running-related injury.

Malaria is one of the deadliest vector-borne diseases in the world. Researchers are developing new genetic and conventional vector control strategies to attempt to limit its burden. Novel control strategies require detailed safety assessment to ensure responsible and successful deployments. Anopheles gambiae sensu stricto (s.s.) and Anopheles coluzzii, two closely related subspecies within the species complex Anopheles gambiae sensu lato (s.l.), are among the dominant malaria vectors in sub-Saharan Africa. These two subspecies readily hybridise and compete in the wild and are also known to have distinct niches, each with spatially and temporally varying carrying capacities driven by precipitation and land use factors. We model the spread and persistence of a population-modifying gene drive system in these subspecies across sub-Saharan Africa by simulating introductions of genetically modified mosquitoes across the African mainland and its offshore islands. We explore transmission of the gene drive between the two subspecies that arise from different hybridisation mechanisms, the effects of both local dispersal and potential wind-aided migration to the spread, and the development of resistance to the gene drive. Given the best current available knowledge on the subspecies' life histories, we find that an introduced gene drive system with typical characteristics can plausibly spread from even distant offshore islands to the African mainland with the aid of wind-driven migration, with resistance beginning to take over within a decade. Our model accounts for regional to continental scale mechanisms, and demonstrates a range of realistic dynamics including the effect of prevailing wind on spread and spatio-temporally varying carrying capacities for subspecies. As a result, it is well-placed to answer future questions relating to mosquito gene drives as important life history parameters become better understood.

Abstract The desire of many engineers is to see their work end up as a final product offering a real benefit to society—for a lecturer/professor at a university, this is a dream often out of reach of the majority. However, the university academic is a changed species from the early days of the binary line between Universities and Polytechnics and when a lecturer meant just that—teaching to future engineers. This article describes the process and experience gained by a university engineer to spin out their research from the university sector and achieve the goal of a product reaching a global audience.

Context: Given the growing interest in digital health interventions (DHI) and increasing number of commercial products targeting youth with ADHD, we conducted a mapping review of the current evidence for DHI for children and adolescents with ADHD. Objective: To identify DHI designed to support or extend ADHD treatment. Data sources: Electronic databases (PubMed, ACM Digital Library, and IEEE Xplore) were searched for studies published in English from January 1, 2004, through January 1, 2022. Search keywords included ADHD and terms for technology (e.g., digital, smartphone, computer) and treatment (e.g., treatment, intervention, cognitive training, neurofeedback). Study selection: Two reviewers reviewed titles, abstracts, and articles. Prior reviews and meta-analyses for two clusters of DHI (cognitive training and neurofeedback) were identified and summarized. The remaining 1,246 records focused on other DHI, and 51 studies representing 16 countries met eligibility criteria. These DHI addressed functioning in domains commonly targeted in treatments for ADHD and were classified based on targeted domains, users, technological platforms, and intended settings. Results: The 51 DHI studies described interventions delivered via serious games or e-learning, the web, mHealth, telehealth, and augmented or virtual reality. DHI targeted a range of domains relevant to ADHD treatment: cognition, social-emotional skills, behavior management, academic/organizational skills, medication adherence, vocational skills, motor behaviors, and clinical care. Twelve well-designed, adequately powered randomized clinical trials reported positive outcomes from interventions delivered using telehealth, the web, mHealth applications, exergaming, and clinician decision-making support tools. Limitations: Keyword selection, terminology usage, and digital libraries in the DHI space were not consistent within or across disciplines, nor across countries, which limited study identification. Few studies had evidence from randomized, controlled trials which limited information on the efficacy of most tools. Conclusions: Research supports the use of several DHI and describes emerging DHI, not yet available for implementation in community settings. Our review provides a map of the current field, identifies gaps and potentials for future research, and highlights the need to increase translation from early designs to robust evidence-based products.

Hollow core fibers have low light attenuation because the light travels through air rather than glass, but other sources of loss have limited the performance so far. Here the authors design and demonstrate a Nested Antiresonant Nodeless hollow core fiber that has losses competitive with standard solid-core fiber at several important wavelengths.

Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are typically associated with poor outcomes. The mechanisms of their aggressiveness are still being investigated. Microsatellite instability (MSI) has recently been found in colorectal NECs showing aberrant methylation of the MLH1 gene and is associated with improved prognosis. We present a 76-year-old lady with an ascending colon tumour showing features of a pT3 N0 R0, large cell NEC (LCNEC) following right hemicolectomy. The adjacent mucosa showed a sessile serrated lesion (SSL) with low-grade dysplasia. Immunohistochemistry showed loss of expression for MLH1 and PMS2 in both the LCNEC and dysplastic SSL. Molecular analysis indicated the sporadic nature of the MLH1 mismatch repair (MMR) protein-deficient status. Our patient did not receive adjuvant therapy and she is alive and disease-free after 34 months follow-up. This finding, similar to early-stage MMR-deficient colorectal adenocarcinoma, is likely practice-changing and will be critical in guiding the appropriate treatment pathway for these patients. We propose that testing of MMR status become routine for early-stage colorectal NECs.

Objective: Growth differentiation factor 15 (GDF15) is known to play a role in feeding, nausea, and body weight, with action through the GFRAL-RET receptor complex in the area postrema (AP) and nucleus tractus solitarius (NTS). To further elucidate the underlying cell type-specific molecular mechanisms downstream of GDF15 signaling, we used a single nuclei RNA sequencing (snRNAseq) approach to profile AP and NTS cellular subtype-specific transcriptomes after systemic GDF15 treatment. Methods: AP and NTS micropunches were used for snRNAseq from Sprague Dawley rats 6 h following GDF15 or saline injection, and Seurat was used to identify cellular subtypes and cell type-specific alterations in gene expression that were due to the direct and secondary effects of systemic GDF15 treatment. Results: Using the transcriptome profile of ∼35,000 individual AP/NTS nuclei, we identified 19 transcriptomically distinct cellular subtypes, including a single population Gfral and Ret positive excitatory neurons, representing the primary site of action for GDF15. A total of ∼600 cell type-specific differential expression events were identified in neurons and glia, including the identification of transcriptome alterations specific to the direct effects of GDF15 in the Gfral-Ret positive excitatory neurons and shared transcriptome alterations across neuronal and glial cell types. Downstream analyses identified shared and cell type-specific alterations in signaling pathways and upstream regulatory mechanisms of the observed transcriptome alterations. Conclusions: These data provide a considerable advance in our understanding of AP and NTS cell type-specific molecular mechanisms associated with GDF15 signaling. The identified cellular subtype-specific regulatory mechanism and signaling pathways likely represent important targets for future pharmacotherapies.

We report on a chemo-dynamical analysis of SPLUS J142445.34−254247.1 (SPLUS J1424−2542), an extremely metal-poor halo star enhanced in elements formed by the rapid neutron-capture process ( r -process). This star was first selected as a metal-poor candidate from its narrowband S-PLUS photometry and followed up spectroscopically in medium resolution with Gemini-South/GMOS, which confirmed its low-metallicity status. High-resolution spectroscopy was gathered with GHOST at Gemini-South, allowing for the determination of the chemical abundances for 36 elements, from carbon to thorium. At [Fe/H] = −3.39, SPLUS J1424−2542 is one of the lowest-metallicity stars with measured Th and has the highest $\mathrm{log}\epsilon (\mathrm{Th}/\mathrm{Eu})$ observed to date, making it part of the “actinide-boost” category of r -process–enhanced stars. The analysis presented here suggests that the gas cloud from which SPLUS J1424−2542 formed must have been enriched by at least two progenitor populations. The light-element ( Z ≤ 30) abundance pattern is consistent with the yields from a supernova explosion of metal-free stars with 11.3–13.4 M _⊙ , and the heavy-element ( Z ≥ 38) abundance pattern can be reproduced by the yields from a neutron star merger (1.66 M _⊙ and 1.27 M _⊙ ) event. A kinematical analysis also reveals that SPLUS J1424−2542 is a low-mass, old halo star with a likely in situ origin, not associated with any known early merger events in the Milky Way.

The Gemini High-resolution Optical SpecTrograph (GHOST) is the newest high-resolution spectrograph to be developed for a large-aperture telescope, recently deployed and commissioned at the Gemini-South telescope. In this paper, we present the first science results from the GHOST spectrograph taking during its commissioning runs. We have observed the bright metal-poor benchmark star HD 122563, along with two stars in the ultrafaint dwarf galaxy Reticulum II (Ret ii ), one of which was previously identified as a candidate member, but did not have a previous detailed chemical abundance analysis. We find that this candidate (GDR3 0928) to be a bona fide member of Ret ii , and from a spectral synthesis analysis it is also revealed to be a CEMP- r star, with significant enhancements in several light elements (C, N, O, Na, Mg, and Si), in addition to featuring an r -process enhancement like many other Ret ii stars. The light-element enhancements in this star resemble the abundance patterns seen in the CEMP-no stars of other ultrafaint dwarf galaxies, and are thought to have been produced by an independent source from the r -process. These unusual abundance patterns are thought to be produced by faint supernovae, which may be produced by some of the earliest generations of stars.

We present new maps of the Milky Way disk showing the distribution of metallicity ([Fe/H]), α -element abundances ([Mg/Fe]), and stellar age, using a sample of 66,496 red giant stars from the final data release (DR17) of the Apache Point Observatory Galactic Evolution Experiment survey. We measure radial and vertical gradients, quantify the distribution functions for age and metallicity, and explore chemical clock relations across the Milky Way for the low- α disk, high- α disk, and total population independently. The low- α disk exhibits a negative radial metallicity gradient of −0.06 ± 0.001 dex kpc ^−1 , which flattens with distance from the midplane. The high- α disk shows a flat radial gradient in metallicity and age across nearly all locations of the disk. The age and metallicity distribution functions shift from negatively skewed in the inner Galaxy to positively skewed at large radius. Significant bimodality in the [Mg/Fe]–[Fe/H] plane and in the [Mg/Fe]–age relation persist across the entire disk. The age estimates have typical uncertainties of ∼0.15 in log(age) and may be subject to additional systematic errors, which impose limitations on conclusions drawn from this sample. Nevertheless, these results act as critical constraints on galactic evolution models, constraining which physical processes played a dominant role in the formation of the Milky Way disk. We discuss how radial migration predicts many of the observed trends near the solar neighborhood and in the outer disk, but an additional more dramatic evolution history, such as the multi-infall model or a merger event, is needed to explain the chemical and age bimodality elsewhere in the Galaxy.

The eighteenth data release (DR18) of the Sloan Digital Sky Survey (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs or “Mappers”: the Milky Way Mapper (MWM), the Black Hole Mapper (BHM), and the Local Volume Mapper. This data release contains extensive targeting information for the two multiobject spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration and scientifically focused components. DR18 also includes ∼25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.

We present the discovery of Boötes V, a new ultra-faint dwarf galaxy (UFD) candidate. This satellite is detected as a resolved overdensity of stars during an ongoing search for new Local Group dwarf galaxy candidates in the UNIONS photometric data set. It has a physical half-light radius of ${26.9}_{-5.4}^{+7.5}$ pc, a V -band magnitude of −4.5 ± 0.4 mag, and resides at a heliocentric distance of approximately 100 kpc. We use Gaia DR3 astrometry to identify member stars, characterize the systemic proper motion, and confirm the reality of this faint stellar system. The brightest star in this system was followed up using Gemini GMOS-N long-slit spectroscopy and is measured to have a metallicity of [Fe/H] = −2.85 ± 0.10 dex and a heliocentric radial velocity of v _r = 5.1 ± 13.4 km s ^−1 . Boötes V is larger (in terms of scale radius), more distant, and more metal-poor than the vast majority of globular clusters. It is likely that Boötes V is an UFD, though future spectroscopic studies will be necessary to definitively classify this object.

ABSTRACT (198): Background: The multi-dose regimen is a known barrier to successful human papillomavirus (HPV) vaccination. Emerging evidence suggests that one vaccine dose could protect against HPV. While there are clear advantages to a single dose schedule, beliefs about vaccine dosage in low and middle income countries (LMICs) are poorly understood. We investigated acceptability of dose-reduction among girls, and parents/guardians of girls, randomised to receive one, two or three doses in an HPV vaccine dose-reduction and immunobridging study (DoRIS trial) in Tanzania. Methods: Semi-structured interviews with girls (n = 19), and parents/guardians of girls (n = 18), enrolled in the study and completing their vaccine course. Results: Most participants said they entrusted decisions about the number of HPV vaccine doses to experts. Random allocation to the different dose groups did not feature highly in the decision to participate in the trial. Given a hypothetical choice, girls generally said they would prefer fewer doses in order to avoid the pain of injections. Parental views were mixed, with most wanting whichever dose was most efficacious. Nonetheless, a few parents equated a higher number of doses with greater protection. Conclusion: Vaccine trials and programmes will need to employ careful messaging to explain that one dose offers sufficient protection against HPV should emerging evidence from ongoing dose-reduction clinical trials support this.

Abstract It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.

Vaccinations to prevent infectious diseases are given to target the body’s innate and adaptive immune systems. In most cases, the potency of a live virus vaccine (LVV) is the most critical measurement of efficacy, though in some cases the quantity of surface antigen on the virus is an equally critical quality attribute. Existing methods to measure the potency of viruses include plaque and TCID50 assays, both of which have very long lead times and cannot provide real time information on the quality of the vaccine during large-scale manufacturing. Here, we report the evaluation of LumaCyte’s Radiance Laser Force Cytology platform as a new way to measure the potency of LVVs in upstream biomanufacturing process in real time and compare this to traditional TCID50 potency. We also assess this new platform as a way to detect adventitious agents, which is a regulatory expectation for the release of commercial vaccines. In both applications, we report the ability to obtain expedited and relevant potency information with strong correlation to release potency methods. Together, our data propose the application of Laser Force Cytology as a valuable process analytical technology (PAT) for the timely measurement of critical quality attributes of LVVs.

When offshore oil and gas infrastructure is no longer needed, it is either removed, partially removed, left in place, or left in place but repurposed. These processes are collectively referred to as decommissioning. Australian legislation requires oil and gas companies to develop acceptable plans for the safe removal of all offshore infrastructure at the end of a project’s life. Over the next 50 years, the liability for this decommissioning in Australia is expected to exceed US$45 billion. Unlike countries such as Norway, the United Kingdom and the Netherlands, Australian decommissioning activities are in their infancy, with only three cases (to date) in Commonwealth waters where infrastructure has been left in place or partially removed as part of decommissioning. Differences between the Australian marine environment and that of other regions around the world where decommissioning-related research is better progressed include very low sedimentation rates, both tropical and temperate habitats, different species composition, low primary production, and frequent tropical cyclones, as well as unique sociodemographic and cultural characteristics. Accordingly, the outcomes of the decision support tools used in other regions to identify preferred decommissioning options may not be equally applicable in Australia. Here we describe research to support risk and impact assessment for offshore decommissioning in Australia, where full removal of infrastructure is the “base case” regulatory default, but other options including partial removal and/or repurposing might provide similar or better outcomes when environmental, social, economic and seafood safety aspects are considered. Based on our review we propose an integrated framework for research needs to meet legislative requirements for decommissioning and identify research gaps that need to be addressed to inform decision-making for decommissioning in the Australian context.

Impulsive behaviour is common in various neuropsychiatric disorders. Here, the authors identify a pathway from the lateral hypothalamus to the ventral hippocampus and the role of melanin-concentrating hormone signaling in these neurons in specifically regulating impulsivity.

Objective: The supramammillary nucleus (SuM) is nestled between the lateral hypothalamus (LH) and the ventral tegmental area (VTA). This neuroanatomical position is consistent with a potential role of this nucleus to regulate ingestive and motivated behavior. Here neuroanatomical, molecular, and behavior approaches are utilized to determine whether SuM contributes to ingestive and food-motivated behavior control. Methods: Through the application of anterograde and retrograde neural tract tracing with novel designer viral vectors, the current findings show that SuM neurons densely innervate the LH in a sex dimorphic fashion. Glucagon-like peptide-1 (GLP-1) is a clinically targeted neuro-intestinal hormone with a well-established role in regulating energy balance and reward behaviors. Here we determine that GLP-1 receptors (GLP-1R) are expressed throughout the SuM of both sexes, and also directly on SuM LH-projecting neurons and investigate the role of SuM GLP-1R in the regulation of ingestive and motivated behavior in male and female rats. Results: SuM microinjections of the GLP-1 analogue, exendin-4, reduced ad libitum intake of chow, fat, or sugar solution in both male and female rats, while food-motivated behaviors, measured using the sucrose motivated operant conditioning test, was only reduced in male rats. These data contrasted with the results obtained from a neighboring structure well known for its role in motivation and reward, the VTA, where females displayed a more potent response to GLP-1R activation by exendin-4. In order to determine the physiological role of SuM GLP-1R signaling regulation of energy balance, we utilized an adeno-associated viral vector to site-specifically deliver shRNA for the GLP-1R to the SuM. Surprisingly, and in contrast to previous results for the two SuM neighboring sites, LH and VTA, SuM GLP-1R knockdown increased food seeking and adiposity in obese male rats without altering food intake, body weight or food motivation in lean or obese, female or male rats. Conclusion: Taken together, these results indicate that SuM potently contributes to ingestive and motivated behavior control; an effect contingent on sex, diet/homeostatic energy balance state and behavior of interest. These data also extend the map of brain sites directly responsive to GLP-1 agonists, and highlight key differences in the role that GLP-1R play in interconnected and neighboring nuclei. Keywords: GLP-1, Supramammillary, Lateral hypothalamic area, Body weight, Operant conditioning

Maximum heart rate (MHR) is widely used in the prescription and monitoring of exercise intensity, and also as a criterion for the termination of sub-maximal aerobic fitness tests in clinical populations. Traditionally, MHR is predicted from an age-based formula, usually 220-age. These formulae, however, are prone to high predictive errors that potentially could lead to inaccurately prescribed or quantified training or inappropriate fitness test termination. In this paper, we used functional data analysis (FDA) to create a new method to predict MHR. It uses heart rate data gathered every 5 seconds during a low intensity, sub-maximal exercise test. FDA allows the use of all the information recorded by monitoring devices in the form of a function, reducing the amount of information needed to generalize a model, besides minimizing the curse of dimensionality. The functional data model created reduced the predictive error by more than 50% compared to current models within the literature. This new approach has important benefits to clinicians and practitioners when using MHR to test fitness or prescribe exercise.

Summary: Multiple cellular pathways have been suggested to be altered by the C9orf72 GGGGCC (G4C2) hexanucleotide repeat expansion (HRE), including aspects of RNA regulation such as nonsense-mediated decay (NMD). Here, we investigate the role that overexpression of UPF1, a protein involved in NMD, plays in mitigating neurotoxicity in multiple models of C9orf72 ALS/FTD. First, we show that NMD is not altered in our endogenous induced pluripotent stem cell (iPSC)-derived spinal neuron (iPSN) model of C9orf72 ALS (C9-ALS) or postmortem motor cortex tissue from C9-ALS patients. Unexpectedly, we find that UPF1 overexpression significantly reduces the severity of known neurodegenerative phenotypes without altering NMD function itself. UPF1 overexpression reduces poly(GP) abundance without altering the amount of repeat RNA, providing a potential mechanism by which UPF1 reduces dipeptide repeat (DPR) protein-mediated toxicity. Together, these findings indicate that UPF1 is neuroprotective in the context of C9-ALS, albeit independent of known UPF1-mediated NMD pathways.