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Abstract Background Dementia is a leading cause of death in developed nations. Despite an often distressing and symptom laden end of life, there are systematic barriers to accessing palliative care in older people dying of dementia. Evidence exists that 70% of people living with severe dementia attend an emergency department (ED) in their last year of life. The aim of this trial is to test whether a Carer End of Life Planning Intervention (CELPI), co-designed by consumers, clinicians and content specialists, improves access to end of life care for older people with severe dementia, using an ED visit as a catalyst for recognising unmet needs and specialist palliative care referral where indicated. Methods A randomised controlled trial (RCT) enrolling at six EDs across three states in Australia will be conducted, enrolling four hundred and forty dyads comprising a person with severe dementia aged ≥ 65 years, and their primary carer. Participants will be randomly allocated to CELPI or the control group. CELPI incorporates a structured carer needs assessment and referral to specialist palliative care services where indicated by patient symptom burden and needs assessment. The primary outcome measure is death of the person with dementia in the carer-nominated preferred location. Secondary outcomes include carer reported quality of life of the person dying of dementia, hospital bed day occupancy in the last 12 months of life, and carer stress. An economic evaluation from the perspective of a health funder will be conducted. Discussion CELPI seeks to support carers and provide optimal end of life care for the person dying of dementia. This trial will provide high level evidence as to the clinical and cost effectiveness of this intervention. Trial registration ACTRN12622000611729 registered 22/04/2022.

River cetaceans are particularly vulnerable to anthropogenic impacts due to their constrained ranges in freshwater systems of China, South Asia, and South America. We undertook an exhaustive review of 280 peer-reviewed papers and grey literature reports (1998-2020) to examine the current status of knowledge regarding these cetaceans and their conservation. We aimed to better understand the scale of threats they face, and to identify and propose priority future efforts to better conserve these species. We found that the species have been studied with varying frequency and that most of the research on threats has focused on habitat degradation and fragmentation (43%, mainly driven by dams and extractive activities such as sand mining and deforestation), and fishery interactions (39%, in the form of bycatch and direct take). These threats occur across all species, but more information is needed, primarily on quantifying the population impacts as a basis for designing mitigation measures. Other threats identified include pollution, vessel collisions, traditional use, and poorly managed tourism. Emerging methods such as environmental DNA and unmanned aerial vehicles are described for studying these species. Promising conservation interventions include cetacean-specific protected areas, natural ex situ protection, community-led conservation, and education programmes. However, transnational political will is required for a step change towards broad-scale protection in freshwater environments. In addition, we propose increasing capacity building, developing management plans, working closely with fishing communities, enhancing public awareness, expanding regional collaborations, and diversifying funding.

Studying the variables that describe the spatial ecology of threatened species allows us to identify and prioritize areas that are critical for species conservation. To estimate the home range and core area of the Endangered (EN) Amazon river dolphin Inia geoffrensis, 23 individuals (6♂, 17♀) were tagged during the rising water period in the Amazon and Orinoco river basins between 2017 and 2018. The satellite tracking period ranged from 24 to 336 d (mean ± SE = 107 ± 15.7 d), and river dolphin movements ranged from 7.5 to 298 km (58 ± 13.4 km). Kernel density estimates were used to determine minimum home ranges at 95% (K95 = 6.2 to 233.9 km2; mean = 59 ± 13.5 km2) and core areas at 50% (K50 = 0.6 to 54.9 km2; mean = 9 ± 2.6 km2). Protected areas accounted for 45% of the K50 estimated core area. We observed dolphin individuals crossing country borders between Colombia and Peru in the Amazon basin, and between Colombia and Venezuela in the Orinoco basin. Satellite tracking allowed us to determine the different uses of riverine habitat types: main rivers (channels and bays, 52% of recorded locations), confluences (32%), lagoons (9.6%), and tributaries (6.2%). Satellite monitoring allowed us to better understand the ecological preferences of the species and demonstrated the importance of maintaining aquatic landscape heterogeneity and spatial connectivity for effective river dolphin conservation.

This study investigated relationships among home reading practices, shared book reading (SBR) behaviors, and child literacy outcomes in young children with cochlear implants in Baltimore, Maryland. Parents (N=18) completed a home reading questionnaire and recorded themselves reading books with their children at home. Shared book reading sessions were coded for interactive reading behaviors. Children's early language skills and literacy skills were also assessed. We explored variability in these behaviors with regard to demographic characteristics and type of book; these exploratory analyses revealed that parents used more literacy teaching techniques when reading the wordless picture book and that parent interaction and engagement and literacy teaching techniques were more frequent with younger children than with older children. While many families frequently used interactive reading behaviors, our analysis did not find significant relationships between the parent behaviors and children's literacy scores. However, there was an interaction between the "amount" of reading and cochlear implant experience such that more cochlear implant experience was associated with better reading outcomes "only" for the group of children who received more reading time. In a sample of young children with cochlear implants, reading time, cochlear implant experience, and child language skills were better predictors of reading outcomes than parents' frequency of SBR behaviors alone.

Marine mammals can play important ecological roles in aquatic ecosystems, and their presence can be key to community structure and function. Consequently, marine mammals are often considered indicators of ecosystem health and flagship species. Yet, historical population declines caused by exploitation, and additional current threats, such as climate change, fisheries bycatch, pollution and maritime development, continue to impact many marine mammal species, and at least 25% are classified as threatened (Critically Endangered, Endangered or Vulnerable) on the IUCN Red List. Conversely, some species have experienced population increases/recoveries in recent decades, reflecting management interventions, and are heralded as conservation successes. To continue these successes and reverse the downward trajectories of at-risk species, it is necessary to evaluate the threats faced by marine mammals and the conservation mechanisms available to address them. Additionally, there is a need to identify evidence-based priorities of both research and conservation needs across a range of settings and taxa. To that effect we: (1) outline the key threats to marine mammals and their impacts, identify the associated knowledge gaps and recommend actions needed; (2) discuss the merits and downfalls of established and emerging conservation mechanisms; (3) outline the application of research and monitoring techniques; and (4) highlight particular taxa/populations that are in urgent need of focus.

The inclusion of forest carbon in climate change mitigation planning requires the development of models able to project potential future carbon stocks—a step beyond traditional monitoring, reporting and verification frameworks. Here, we updated and expanded a high-resolution forest carbon modelling approach previously developed for the state of Maryland to 11 states in the Regional Greenhouse Gas Initiative (RGGI) domain, which includes Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont. In this study, we employ an updated version of the Ecosystem Demography (ED) model, an improved lidar initialization strategy, and an expanded calibration/validation approach. High resolution (90 m) wall-to-wall maps of present aboveground carbon, aboveground carbon sequestration potential, aboveground carbon sequestration potential gap (CSPG), and time to reach sequestration potential were produced over the RGGI domain where airborne lidar data were available, including 100% of eight states, 62% of Maine, 12% of New Jersey, and 0.65% of New York. For the eight states with complete data, an area of 228 552 km ^2 , the contemporary forest aboveground carbon stock is estimated to be 1134 Tg C, and the forest aboveground CSPG is estimated to be larger at >1770 Tg C. Importantly, these estimates of the potential for added aboveground carbon sequestration in forests are spatially resolved, are further partitioned between continued growth of existing trees and new afforested/reforested areas, and include time estimates for realization. They are also assessed for sensitivity to potential changes in vegetation productivity and disturbance rate in response to climate change. The results from this study are intended as input into regional, state, and local planning efforts that consider future climate mitigation in forests along with other land-use considerations.

Forests are important ecosystems that are under increasing pressure from human use and environmental change, and have a significant ability to remove carbon dioxide from the atmosphere, and are therefore the focus of policy efforts aimed at reducing deforestation and degradation as well as increasing afforestation and reforestation for climate mitigation. Critical to these efforts is the accurate monitoring, reporting and verification of current forest cover and carbon stocks. For planning, the additional step of modeling is required to quantitatively estimate forest carbon sequestration potential in response to alternative land-use and management decisions. To be most useful and of decision-relevant quality, these model estimates must be at very high spatial resolution and with very high accuracy to capture important heterogeneity on the land surface and connect to monitoring efforts. Here, we present results from a new forest carbon monitoring and modeling system that combines high-resolution remote sensing, field data, and ecological modeling to estimate contemporary above-ground forest carbon stocks, and project future forest carbon sequestration potential for the state of Maryland at 90 m resolution. Statewide, the contemporary above-ground carbon stock was estimated to be 110.8 Tg C (100.3–125.8 Tg C), with a corresponding mean above-ground biomass density of 103.7 Mg ha ^−1 which was within 2% of independent empirically-based estimates. The forest above-ground carbon sequestration potential for the state was estimated to be much larger at 314.8 Tg C, and the forest above-ground carbon sequestration potential gap (i.e. potential-current) was estimated to be 204.1 Tg C, nearly double the current stock. These results imply a large statewide potential for future carbon sequestration from afforestation and reforestation activities. The high spatial resolution of the model estimates underpinning these totals demonstrate important heterogeneity across the state and can inform prioritization of actual afforestation/reforestation opportunities. With this approach, it is now possible to quantify both the forest carbon stock and future carbon sequestration potential over large policy relevant areas with sufficient accuracy and spatial resolution to significantly advance planning.

Nitrate, the most oxidized form of nitrogen, is regulated to protect people and animals from harmful levels as there is a large over abundance due to anthropogenic factors. Widespread field testing for nitrate could begin to address the nitrate pollution problem, however, the Cadmium Reduction Method, the leading certified method to detect and quantify nitrate, demands the use of a toxic heavy metal. An alternative, the recently proposed Environmental Protection Agency Nitrate Reductase Nitrate-Nitrogen Analysis Method, eliminates this problem but requires an expensive proprietary spectrophotometer. The development of an inexpensive portable, handheld photometer will greatly expedite field nitrate analysis to combat pollution. To accomplish this goal, a methodology for the design, development, and technical validation of an improved open-source water testing platform capable of performing Nitrate Reductase Nitrate-Nitrogen Analysis Method. This approach is evaluated for its potential to i) eliminate the need for toxic chemicals in water testing for nitrate and nitrite, ii) reduce the cost of equipment to perform this method for measurement for water quality, and iii) make the method easier to carryout in the field. The device is able to perform as well as commercial proprietary systems for less than 15% of the cost for materials. This allows for greater access to the technology and the new, safer nitrate testing technique.

Infants diagnosed with autism spectrum disorder (autism) have difficulty engaging in social communication and interactions with others and often experience language impairment. The use of infant-directed speech (IDS), which is the speech register used when interacting with infants, is associated with infant language and socio-communicative development. The aim of this study was twofold; the first aim was to scope the literature to determine if evidence exists for differences between the IDS caregivers use to infants at high-risk or those later diagnosed with autism, and the IDS typically spoken to neurotypical infants. The second aim was to investigate if any IDS characteristics used by caregivers of high-risk or diagnosed infant populations predicted language development. Twenty-six studies were included and provided evidence that high-risk and later diagnosed infants are exposed to similar amounts of IDS as their neurotypical peers. There is evidence, however, that the IDS used with high-risk and later diagnosed infants may comprise shorter utterances, more action-directing content, fewer questions, more attention bids, and more follow-in commenting. There is also evidence that more attention bids and follow-in commenting used to infants at high risk or those later diagnosed with autism were associated with better language abilities longitudinally.

ABSTRACT: Background: There is a growing interest in the development and application of mid-field (0.55T) for cardiovascular magnetic resonance (CMR), including flow imaging. However, aortic flow imaging at 0.55T has limited signal-to-noise ratio (SNR), especially in diastolic phases where there is reduced inflow-driven contrast for spoiled gradient recalled echo (GRE) sequences. The low SNR can limit the accuracy of flow and regurgitant fraction measurements. Methods: In this work, we developed a two-dimensional phase contrast (PC) acquisition with balanced steady-state free precession (bSSFP), termed PC-SSFP, for flow imaging and quantification at 0.55T. This PC-SSFP approach precisely nulls the zeroth and first gradient moments at both the echo time (TE) and repetition time, except for the flow-encoded acquisition, for which the first gradient moment at the TE is determined by the velocity encoding. Our proposed sequence was tested in both phantoms and in healthy volunteers (n = 11), to measure aortic flow. In volunteers, both a breath-hold (bh) and a free-breathing (fb) protocol, with averaging to increase SNR, were obtained. Total flow, peak flow, cardiac output, and SNR were compared for PC-SSFP and PC-GRE. Stroke volumes were also measured and compared to planimetry method. Results: In a phantom, SNR was significantly higher using PC-SSFP compared to PC-GRE (25.5 ± 9.6 vs 8.2 ± 2.9), and the velocity measurements agreed well (R = 1.00). In healthy subjects, for both bh and fb protocols, PC-SSFP measured accurate peak flow (fb: R = 0.99, bh: R = 0.96) and cardiac output (fb: R = 0.98, bh: R = 0.88), compared to PC-GRE, accurate stroke volume (fb: R = 0.94, bh: R = 0.97), compared to planimetry measurement, and offered constant high SNR (fb: 28 ± 9 vs 18 ± 6, bh: 24 ± 7 vs 11 ± 3) over the cardiac cycle in 11 subjects. Conclusion: PC-SSFP is a more reliable evaluation tool for aortic flow quantification, when compared to the conventional PC-GRE method at 0.55T, providing higher SNR, and thus potentially more accurate flows.

Abstract Genetically-encoded biosensors based on a single fluorescent protein are widely used to visualize analyte levels or enzymatic activities in cells, though usually to monitor relative changes rather than absolute values. We report photochromism-enabled absolute quantification (PEAQ) biosensing, a method that leverages the photochromic properties of biosensors to provide an absolute measure of the analyte concentration or activity. We develop proof-of-concept photochromic variants of the popular GCaMP family of Ca2+ biosensors, and show that these can be used to resolve dynamic changes in the absolute Ca2+ concentration in live cells. We also develop intermittent quantification, a technique that combines absolute aquisitions with fast fluorescence acquisitions to deliver fast but fully quantitative measurements. We also show how the photochromism-based measurements can be expanded to situations where the absolute illumination intensities are unknown. In principle, PEAQ biosensing can be applied to other biosensors with photochromic properties, thereby expanding the possibilities for fully quantitative measurements in complex and dynamic systems.

Junín virus (JUNV), a New World arenavirus, is a rodent-borne virus and the causative agent of Argentine hemorrhagic fever. Humans become infected through exposure to rodent host secreta and excreta and the resulting infection can lead to an acute inflammatory disease with significant morbidity and mortality. Little is understood about the molecular pathogenesis of arenavirus hemorrhagic fever infections. We utilized Reverse Phase Protein Microarrays (RPPA) to compare global alterations in the host proteome following infection with an attenuated vaccine strain, Candid#1 (CD1), and the most parental virulent strain, XJ13, of JUNV in a human cell culture line. Human small airway epithelial cells were infected with CD1 or XJ13 at an MOI of 10, or mock infected. To determine proteomic changes at early timepoints (T = 1, 3, 8 and 24 h), the JUNV infected or mock infected cells were lysed in compatible buffers for RPPA. Out of 113 proteins that were examined by RPPA, 14 proteins were significantly altered following JUNV infection. Several proteins were commonly phosphorylated between the two strains and these correspond to entry and early replication events, to include p38 mitogen-activated protein kinase (MAPK), heat shock protein 27 (HSP27), and nuclear factor kappa B (NFκB). We qualitatively confirmed the alterations of these three proteins following infection by western blot analysis. We also determined that the inhibition of either p38 MAPK, with the small molecule inhibitor SB 203580 or siRNA knockdown, or HSP27, by siRNA knockdown, significantly decreases JUNV replication. Our data suggests that HSP27 phosphorylation at S82 upon virus infection is dependent on p38 MAPK activity. This work sheds light on the nuances of arenavirus replication.