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Abstract Background Aboriginal people are known to be under-recorded in routinely collected datasets in Australia. This study examined methods for enhancing the reporting of cancer incidence among Aboriginal people using linked data methodologies. Methods Invasive cancers diagnosed in New South Wales (NSW), Australia, in 2010–2014 were identified from the NSW Cancer Registry (NSWCR). The NSWCR data were linked to the NSW Admitted Patient Data Collection, the NSW Emergency Department Data Collection and the Australian Coordinating Register Cause of Death Unit Record File. The following methods for enhancing the identification of Aboriginal people were used: ‘ever-reported’, ‘reported on most recent record’, ‘weight of evidence’ and ‘multi-stage median’. The impact of these methods on the number of cancer cases and age-standardised cancer incidence rates (ASR) among Aboriginal people was explored. Results Of the 204,948 cases of invasive cancer, 2703 (1.3%) were recorded as Aboriginal on the NSWCR. This increased with enhancement methods to 4184 (2.0%, ‘ever’), 3257 (1.6%, ‘most recent’), 3580 (1.7%, ‘weight of evidence’) and 3583 (1.7%, ‘multi-stage median’). Enhancement was generally greater in relative terms for males, people aged 25–34 years, people with cancers of localised or unknown degree of spread, people living in urban areas and areas with less socio-economic disadvantage. All enhancement methods increased ASRs for Aboriginal people. The weight of evidence method increased the overall ASR by 42% for males (894.1 per 100,000, 95% CI 844.5–945.4) and 27% for females (642.7 per 100,000, 95% CI 607.9–678.7). Greatest relative increases were observed for melanoma and prostate cancer incidence (126 and 63%, respectively). ASRs for prostate and breast cancer increased from below to above the ASRs of non-Aboriginal people with enhancement of Aboriginal status. Conclusions All data linkage methods increased the number of cancer cases and ASRs for Aboriginal people. Enhancement varied by demographic and cancer characteristics. We considered the weight of evidence method to be most suitable for population-level reporting of cancer incidence among Aboriginal people. The impact of enhancement on disparities in cancer outcomes between Aboriginal and non-Aboriginal people should be further examined.

Abstract Ergometrine is recommended for use in the medical treatment of postpartum hemorrhage. Ergometrine can occasionally precipitate myocardial ischemia in the setting of significant anemia in women without preexisting cardiac risk factors, and it is important to recognize and treat myocardial ischemia in affected patients to prevent severe complications.

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015–2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM2.5, PM10, PMC (coarse fraction of PM), NO2, SO2, NOx, CO, O3 and the total gaseous oxidant (OX = NO2 + O3) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015–2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO2 and NOx concentrations and peoples’ mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality.As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO2 and between 30% and 40% in mean PM2.5 concentrations over 2020 full lockdown compared to the same period in 2015–2019. However, PM2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO2/CO ratio). Some Chinese cities showed similar increases in PM2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of ~70%. The SO2 anomalies were negative for 2020 compared to 2015–2019 (between ~25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to ~40%. The NO2/CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO2 decrease due to the general reduction in mobility (ratio of ~60%). Analysis of the total oxidant (OX = NO2 + O3) showed that primary NO2 emissions at urban locations were greater than the O3 production, whereas at background sites, OX was mostly driven by the regional contributions rather than local NO2 and O3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required.

In order to synthesize changes in pollinating insect communities across space and time, it is necessary to understand whether, and how, sampling methods influence assessments of community patterns. We compared how two common sampling methods—yellow combined flight traps and net sampling—influence our understanding of the species richness, abundance and composition of wild bees and hoverflies, and addressed whether these patterns resulted from potentially biased sampling of individuals or species with different types of functional traits. We sampled bee and hoverfly communities in six sites over three seasons in Saxony-Anhalt, Germany. We captured more species and individuals of bees with traps and more species and individuals of hoverflies with net sampling. However, rarefied richness results were less dramatic between the sampling methods for bees and were not different between the sampling methods for hoverflies. Thus, differences in species richness across sampling methods were mostly due to differences in the number of individuals captured in the different methods. We captured more small-sized bees and hoverflies with traps. We tested if the different methods collected individuals and species with different functional traits, such as nesting preferences, sociality and flower specialization for bees and floral preference, migratory status and habitat preference for hoverflies. For most traits, we collected more individuals but not more species with a certain trait in the different methods. This was mainly due to a high abundance of one species being collected in the different methods. These results suggest that the best methodology depends on the aim of the survey, and that the methods cannot be easily combined into synthesis research. Our results have implications for the development of monitoring schemes for pollinators and for synthesis of trends that can identify threats to pollinators and inform research of pollinator conservation strategies.

Background: There are limited data comparing remote magnetic navigation (RMN) to contemporary techniques of manual-guided ventricular arrhythmia (VA) catheter ablation. Objectives: We compared acute and long-term outcomes of VA ablation guided by either RMN or contemporary manual techniques in patients with structural heart disease. Methods: From 2010–2019, 192 consecutive patients, with ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM) underwent catheter ablation for sustained ventricular tachycardia (VT) or premature ventricular complexes (PVCs), using either RMN (n = 60) or manual (n = 132) guided techniques. Acute success and VA-free survival were compared. Results: In ICM, acute procedural success was comparable between the 2 techniques (manual 43.5% vs. RMN 29%, P = 0.11), as was VA-free survival (manual 83% vs. RMN 74%, P = 0.88), and survival free from cardiac transplantation and all-cause mortality (manual 88% vs. RMN 87%, P = 0.47), both at 12-months after final ablation. In NICM, manual compared to RMN guided, had superior acute procedural success (manual 46% vs. RMN 19%, P = 0.003) and VA-free survival 12-months after final ablation (manual 79% vs. RMN 41%, P = 0.004), but comparable survival free from cardiac transplantation and all-cause mortality 12-months after final ablation (manual 95% vs. RMN 90%, P = 0.52). Procedural duration was shorter in both subgroups undergoing manual guided ablation, whereas fluoroscopy dose and complication rates were comparable. Conclusion: RMN provides similar outcomes to manual ablation in patients with ICM. In NICM however, acute success, and long-term VA-free survival was better with manual ablation. Prospective, multi-centre randomised trials comparing contemporary manual and RMN systems for VA catheter ablation are needed.

Abstract Many countries allow lawsuits to hold responsible parties liable for the environmental harm they cause. Such litigation remains largely untested in most biodiversity hotspots and is rarely used in response to leading drivers of biodiversity loss, including illegal wildlife trade. Yet, liability litigation is a potentially ground‐breaking conservation strategy to remedy harm to biodiversity by seeking legal remedies such as species rehabilitation, public apologies, habitat conservation and education, with the goal of making the injured parties ‘whole’. However, precedent cases, expert guidance, and experience to build such conservation lawsuits is nascent in most countries. We propose a simplified framework for developing conservation lawsuits across countries and conservation contexts. We explain liability litigation in terms of three dimensions: (1) defining the harm that occurred, (2) identifying appropriate remedies to that harm, and (3) understanding what remedies the law and courts will allow. We illustrate the framework via a hypothetical lawsuit against an illegal orangutan trader in Indonesia. We highlight that conservationists’ expertise is essential to characterizing harm and identifying remedies, and could more actively contribute to strategic, science‐based litigation. This would identify priority contexts, target defendants responsible for egregious harm, propose novel and meaningful remedies, and build new transdisciplinary collaborations.

Summary: Background: Data on influenza community burden and transmission are important to plan interventions especially in resource-limited settings. However, data are limited, particularly from low-income and middle-income countries. We aimed to evaluate the community burden and transmission of influenza in a rural and an urban setting in South Africa. Methods: In this prospective cohort study approximately 50 households were selected sequentially from both a rural setting (Agincourt, Mpumalanga Province, South Africa; with a health and sociodemographic surveillance system) and an urban setting (Klerksdorp, Northwest Province, South Africa; using global positioning system data), enrolled, and followed up for 10 months in 2017 and 2018. Different households were enrolled in each year. Households of more than two individuals in which 80% or more of the occupants agreed to participate were included in the study. Nasopharyngeal swabs were collected twice per week from participating household members irrespective of symptoms and tested for influenza using real-time RT-PCR. The primary outcome was the incidence of influenza infection, defined as the number of real-time RT-PCR-positive episodes divided by the person-time under observation. Household cumulative infection risk (HCIR) was defined as the number of subsequent infections within a household following influenza introduction. Findings: 81 430 nasopharyngeal samples were collected from 1116 participants in 225 households (follow-up rate 88%). 917 (1%) tested positive for influenza; 178 (79%) of 225 households had one or more influenza-positive individual. The incidence of influenza infection was 43·6 (95% CI 39·8–47·7) per 100 person-seasons. 69 (17%) of 408 individuals who had one influenza infection had a repeat influenza infection during the same season. The incidence (67·4 per 100 person-seasons) and proportion with repeat infections (22 [23%] of 97 children) were highest in children younger than 5 years and decreased with increasing age (p

Skin fibrosis still constitutes an unmet clinical need. Although pharmacological strategies are at the forefront of scientific and technological research and innovation, their clinical translation is hindered by the poor predictive capacity of the currently available in vitro fibrosis models. Indeed, customarily utilised in vitro scarring models are conducted in a low extracellular matrix milieu, which constitutes an oxymoron for the in-hand pathophysiology. Herein, we coupled macromolecular crowding (enhances and accelerates extracellular matrix deposition) with transforming growth factor β1 (TGFβ1; induces trans-differentiation of fibroblasts to myofibroblasts) in human dermal fibroblast cultures to develop a skin fibrosis in vitro model and to screen a range of anti-fibrotic families (corticosteroids, inhibitors of histone deacetylases, inhibitors of collagen crosslinking, inhibitors of TGFβ1 and pleiotropic inhibitors of fibrotic activation). Data obtained demonstrated that macromolecular crowding combined with TGFβ1 significantly enhanced collagen deposition and myofibroblast transformation. Among the anti-fibrotic compounds assessed, trichostatin A (inhibitors of histone deacetylases); serelaxin and pirfenidone (pleiotropic inhibitors of fibrotic activation); and soluble TGFβ receptor trap (inhibitor of TGFβ signalling) resulted in the highest decrease of collagen type I deposition (even higher than triamcinolone acetonide, the gold standard in clinical practice). This study further advocates the potential of macromolecular crowding in the development of in vitro pathophysiology models.

Southern Ocean ecosystems are globally important. Processes in the Antarctic atmosphere, cryosphere, and the Southern Ocean directly influence global atmospheric and oceanic systems. Southern Ocean biogeochemistry has also been shown to have global importance. In contrast, ocean ecological processes are often seen as largely separate from the rest of the global system. In this paper, we consider the degree of ecological connectivity at different trophic levels, linking Southern Ocean ecosystems with the global ocean, and their importance not only for the regional ecosystem but also the wider Earth system. We also consider the human system connections, including the role of Southern Ocean ecosystems in supporting society, culture, and economy in many nations, influencing public and political views and hence policy. Rather than Southern Ocean ecosystems being defined by barriers at particular oceanic fronts, ecological changes are gradual due to cross-front exchanges involving oceanographic processes and organism movement. Millions of seabirds and hundreds of thousands of cetaceans move north out of polar waters in the austral autumn interacting in food webs across the Southern Hemisphere, and a few species cross the equator. A number of species migrate into the east and west ocean-basin boundary current and continental shelf regions of the major southern continents. Human travel in and out of the Southern Ocean region includes fisheries, tourism, and scientific vessels in all ocean sectors. These operations arise from many nations, particularly in the Northern Hemisphere, and are important in local communities as well as national economic, scientific, and political activities. As a result of the extensive connectivity, future changes in Southern Ocean ecosystems will have consequences throughout the Earth system, affecting ecosystem services with socio-economic impacts throughout the world. The high level of connectivity also means that changes and policy decisions in marine ecosystems outside the Southern Ocean have consequences for ecosystems south of the Antarctic Polar Front. Knowledge of Southern Ocean ecosystems and their global connectivity is critical for interpreting current change, projecting future change impacts, and identifying integrated strategies for conserving and managing both the Southern Ocean and the broader Earth system.

Summary: Background: Uncertainty remains concerning the association of blood cholesterol with the risk of subsequent dementia. Using data from people with lipid measurements in the UK Clinical Practice Research Datalink (CPRD), we examined the association between blood lipid levels and dementia (both vascular and non-vascular, including Alzheimer's disease) by age at first measurement of blood lipids and duration of follow-up. Methods: We studied a cohort from the UK CPRD of people aged 40 years or older with a first total cholesterol recording between Jan 1, 1992, and Dec 31, 2009. Follow-up was until the first record of dementia, the last data collection date, patient death or transfer out of the practice, or Jan 5, 2015, whichever was earliest. We excluded individuals with a record of dementia before the total cholesterol measurement. We used Poisson regression to examine the association between baseline total cholesterol, LDL cholesterol and HDL cholesterol, and triglycerides and incident dementia diagnosis. Analyses were stratified by age at first measurement (

Hypertrophy can be operationally defined as an increase in the axial cross-sectional area of a muscle fiber or whole muscle, and is due to increases in the size of pre-existing muscle fibers. Hypertrophy is a desired outcome in many sports. For some athletes, muscular bulk and, conceivably, the accompanying increase in strength/power, are desirable attributes for optimal performance. Moreover, bodybuilders and other physique athletes are judged in part on their muscular size, with placings predicated on the overall magnitude of lean mass. In some cases, even relatively small improvements in hypertrophy might be the difference between winning and losing in competition for these athletes. This position stand of leading experts in the field synthesizes the current body of research to provide guidelines for maximizing skeletal muscle hypertrophy in an athletic population. The recommendations represent a consensus of a consortium of experts in the field, based on the best available current evidence. Specific sections of the paper are devoted to elucidating the constructs of hypertrophy, reconciliation of acute vs long-term evidence, and the relationship between strength and hypertrophy to provide context to our recommendations.

Assays for rapid biosafety level 2 (BSL2) evaluation of neutralizing properties of antibodies acquired via natural infection or through vaccination is urgently needed. Here, we propose a combinatorial approach in which sera are screened for SARS-CoV-2 spike protein (S) binding using a cell-based immunofluorescent (CBI) assay, and positive samples are further evaluated in a pseudotyped viral multicycle infection-mimicking protocol under BSL2 conditions.

This research investigates the capability of field-based spectroscopy (350–2500 nm) for discriminating banana plants (Cavendish subgroup Williams) infested with spider mites from those unaffected. Spider mites are considered a major threat to agricultural production, as they occur on over 1000 plant species, including banana plant varieties. Plants were grown under a controlled glasshouse environment to remove any influence other than the imposed treatment (presence or absence of spider mites). The spectroradiometer measurements were undertaken with a leaf clip over three infestation events. From the resultant spectral data, various classification models were evaluated including partial least squares discriminant analysis (PLSDA), K-nearest neighbour, support vector machines and back propagation neural network. Wavelengths found to have a significant response to the presence of spider mites were extracted using competitive adaptive reweighted sampling (CARS), sub-window permutation analysis (SPA) and random frog (RF) and benchmarked using the classification models. CARS and SPA provided high detection success (86% prediction accuracy), with the wavelengths found to be significant corresponding with the red edge and near-infrared portions of the spectrum. As there is limited access to operational commercial hyperspectral imaging and additional complexity, a multispectral camera (Sequoia) was assessed for detecting spider mite impacts on banana plants. Simulated multispectral bands were able to provide a high level of detection accuracy (prediction accuracy of 82%) based on a PLSDA model, with the near-infrared band being most important, followed by the red edge, green and red bands. Multispectral vegetation indices were trialled using a simple threshold-based classification method using the green normalised difference vegetation index (GNDVI), which achieved 82% accuracy. This investigation determined that remote sensing approaches can provide an accurate method of detecting mite infestations, with multispectral sensors having the potential to provide a more commercially accessible means of detecting outbreaks.

In the Australian summer season of 2022, exceptional rainfall events occurred in Southeast Queensland and parts of New South Wales, leading to extensive flooding of rural and urban areas. Here, we map the extent of flooding in the city of Brisbane and evaluate the change in electricity usage as a proxy for flood impact using VIIRS nighttime brightness imagery. Scanning a wide range of possible sensors, we used pre-flood and peak-flood PlanetScope imagery to map the inundated areas, using a new spectral index we developed, the Normalized Difference Inundation Index (NDII), which is based on changes in the NIR reflectance due to sediment-laden flood waters. We compared the Capella-Space X-band/HH imaging radar data captured at peak-flood date to the PlanetScope-derived mapping of the inundated areas. We found that in the Capella-Space image, significant flooded areas identified in PlanetScope imagery were omitted. These omission errors may be partly explained by the use of a single-date radar image, by the X-band, which is partly scattered by tree canopy, and by the SAR look angle under which flooded streets may be blocked from the view of the satellite. Using VIIRS nightly imagery, we were able to identify grid cells where electricity usage was impacted due to the floods. These changes in nighttime brightness matched both the inundated areas mapped via PlanetScope data as well as areas corresponding with decreased electricity loads reported by the regional electricity supplier. Altogether we demonstrate that using a variety of optical and radar sensors, as well as nighttime and daytime sensors, enable us to overcome data gaps and better understand the impact of flood events. We also emphasize the importance of high temporal revisit times (at least twice daily) to more accurately monitor flood events.

Global warming and over-enrichment of freshwater systems have led to an increase in harmful cyanobacterial blooms (cyanoHABs), affecting human and animal health. The aim of this systematic map was to detail the current literature surrounding cyanotoxin poisonings in terrestrial wildlife and identify possible improvements to reports of morbidity and mortality from cyanotoxins. A systematic search was conducted using the electronic databases Scopus and Web of Science, yielding 5059 published studies identifying 45 separate case reports of wildlife poisonings from North America, Africa, Europe, and Asia. Currently, no gold standard for the diagnosis of cyanotoxin intoxication exists for wildlife, and we present suggested guidelines here. These involved immunoassays and analytical chemistry techniques to identify the toxin involved, PCR to identify the cyanobacterial species involved, and evidence of ingestion or exposure to cyanotoxins in the animals affected. Of the 45 cases, our recommended methods concurred with 48.9% of cases. Most often, cases were investigated after a mortality event had already occurred, and where mitigation was implemented, only three cases were successful in their efforts. Notably, only one case of invasive cyanobacteria was recorded in this review despite invasive species being known to occur throughout the globe; this could explain the underreporting of invasive cyanobacteria. This systematic map highlights the perceived absence of robust detection, surveillance, and diagnosis of cyanotoxin poisoning in wildlife. It may be true that wildlife is less susceptible to these poisoning events; however, the true rates of poisoning are likely much more than is reported in the literature.

Remotely sensed morphological traits have been used to assess functional diversity of forests. This approach is potentially spatial-scale-independent. Lidar data collected from the ground or by drone at a high point density provide an opportunity to consider multiple ecologically meaningful traits at fine-scale ecological units such as individual trees. However, high-spatial-resolution and multi-trait datasets used to calculate functional diversity can produce large volumes of data that can be computationally resource demanding. Functional diversity can be derived through a trait probability density (TPD) approach. Computing TPD in a high-dimensional trait space is computationally intensive. Reductions of the number of dimensions through trait selection and principal component analysis (PCA) may reduce the computational load. Trait selection can facilitate identification of ecologically meaningful traits and reduce inter-trait correlation. This study investigates whether kernel density estimator (KDE) or one-class support vector machine (SVM) may be computationally more efficient in calculating TPD. Four traits were selected for input into the TPD: canopy height, effective number of layers, plant to ground ratio, and box dimensions. When simulating a high-dimensional trait space, we found that TPD derived from KDE was more efficient than using SVM when the number of input traits was high. For five or more traits, applying dimension reduction techniques (e.g., PCA) are recommended. Furthermore, the kernel size for TPD needs to be appropriate for the ecological target unit and should be appropriate for the number of traits. The kernel size determines the required number of data points within the trait space. Therefore, 3–5 traits require a kernel size of at least 7×7pixels. This study contributes to improving the quality of TPD calculations based on traits derived from remote sensing data. We provide a set of recommendations based on our findings. This has the potential to improve reliability in identifying biodiversity hotspots.

Objective To assess associations of health-related quality of life (HRQoL) with patient profile, resource use, cardiovascular (CV) events and mortality in stable patients post-myocardial infarction (MI).Methods The global, prospective, observational TIGRIS Study enrolled 9126 patients 1–3 years post-MI. HRQoL was assessed at enrolment and 6-month intervals using the patient-reported EuroQol-5 dimension (EQ-5D) questionnaire, with scores anchored at 0 (worst possible) and 1 (perfect health). Resource use, CV events and mortality were recorded during 2-years’ follow-up. Regression models estimated the associations of index score at enrolment with patient characteristics, resource use, CV events and mortality over 2-years’ follow-up.Results Among 8978 patients who completed the EQ-5D questionnaire, 52% reported ‘some’ or ‘severe’ problems on one or more health dimensions. Factors associated with a lower index score were: female sex, older age, obesity, smoking, higher heart rate, less formal education, presence of comorbidity (eg, angina, stroke), emergency room visit in the previous 6 months and non-ST-elevation MI as the index event. Compared with an index score of 1 at enrolment, a lower index score was associated with higher risk of all-cause death, with an adjusted rate ratio of 3.09 (95% CI 2.20 to 4.31), and of a CV event, with a rate ratio of 2.31 (95% CI 1.76 to 3.03). Patients with lower index score at enrolment had almost two times as many hospitalisations over 2-years’ follow-up.Conclusions Clinicians managing patients post-acute coronary syndrome should recognise that a poorer HRQoL is clearly linked to risk of hospitalisations, major CV events and death.Trial registration number ClinicalTrials.gov Registry (NCT01866904) (https://clinicaltrials.gov).

Introduction Nitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate headache and outcome in patients with acute stroke.Materials and methods Patients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the efficacy of nitric oxide in stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give OR and mean difference (MD) with 95% CI.Results In 4011 patients, headache was more common in GTN than control (360, 18.0% vs 170, 8.5%; p

Background. Real-world evidence can be a valuable tool when clinical trial data are incomplete or uncertain. Bevacizumab was adopted as first-line therapy for metastatic colorectal cancer (mCRC) based on significant survival improvements in initial clinical trials; however, survival benefit diminished in subsequent analyses. Consequently, there is uncertainty surrounding the cost-effectiveness of bevacizumab therapy achieved in practice. Objective. To assess real-world cost-effectiveness of first-line bevacizumab with irinotecan-based chemotherapy versus irinotecan-based chemotherapy alone for mCRC in British Columbia (BC), Saskatchewan, and Ontario, Canada. Methods. Using provincial cancer registries and linked administrative databases, we identified mCRC patients who initiated publicly funded irinotecan-based chemotherapy, with or without bevacizumab, in 2000 to 2015. We compared bevacizumab-treated patients to historical controls (treated before bevacizumab funding) and contemporaneous controls (receiving chemotherapy without bevacizumab), using inverse-probability-of-treatment weighting with propensity scores to balance baseline covariates. We calculated incremental cost-effectiveness ratios (ICER) using 5-year cost and survival adjusted for censoring, with bootstrapping to characterize uncertainty. We also conducted one-way sensitivity analysis for key drivers of cost-effectiveness. Results. The cohorts included 12,112 (Ontario), 1,161 (Saskatchewan), and 2,977 (BC) patients. Bevacizumab significantly increased treatment costs, with mean ICERs between $78,000 and $84,000/LYG (life-year gained) in the contemporaneous comparisons and $75,000 and $101,000/LYG in the historical comparisons. Reducing the cost of bevacizumab by 50% brought ICERs in all comparisons below $61,000/LYG. Limitations. Residual confounding in observational data may bias results, while the use of original list prices overestimates current bevacizumab cost. Conclusion. The addition of bevacizumab to irinotecan-based chemotherapy extended survival for mCRC patients but at significant cost. At original list prices bevacizumab can only be considered cost-effective with certainty at a willingness-to-pay threshold over $100,000/LYG, but price reductions or discounts have a significant impact on cost-effectiveness.

Background Female sex was not included among the high bleeding risk (HBR) criteria by the Academic Research Consortium (ARC) as it remains unclear whether it constitutes an HBR condition after percutaneous coronary intervention. We investigated whether female sex associates with HBR and assessed the performance of ARC HBR criteria separately in women and men. Methods and Results Among all consecutive patients undergoing percutaneous coronary intervention between 2009 and 2018, bleeding occurrences up to 1 year were prospectively collected and centrally adjudicated. All but one of the originally defined ARC HBR criteria were assessed, and the ARC HBR score generated accordingly. Among 16 821 patients, 25.6% were women. Compared with men, women were older and had lower creatinine clearance and hemoglobin values. After adjustment, female sex was independently associated with access‐site (adjusted hazard ratio, 2.14; 95% CI, 1.22–3.74; P=0.008) but not with overall or non–access‐site 1‐year Bleeding Academic Research Consortium 3 or 5 bleeding. This association remained consistent when the femoral but not the radial approach was chosen. The ARC HBR score discrimination, using the original criteria, was lower among women than men (c‐index 0.644 versus 0.688; P=0.048), whereas a revised ARC HBR score, in which age, creatinine clearance, and hemoglobin were modeled as continuous rather than dichotomized variables, performed similarly in both sexes. Conclusions Female sex is an independent predictor for access‐site bleeding but not for overall bleeding events at 1 year after percutaneous coronary intervention. The ARC HBR framework shows an overall good performance in both sexes, yet is lower in women than men, attributable to dichotomization of age, creatinine clearance, and hemoglobin values, which are differently distributed between sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Emphasis on continuous infant sleep overnight may be driven by parental concern of risk to child mental health outcomes. The Mercy Pregnancy and Emotional Wellbeing Study (MPEWS) examined whether infant sleep at 6 and 12 months postpartum predicts anxiety disorders at 2-4 years, and whether this is moderated by maternal depression, active physical comforting (APC) or maternal cognitions about infant sleep. Data included 349 women and infants. Infant sleep was measured using the Brief Infant Sleep Questionnaire and child anxiety disorders by the Preschool Age Psychiatric Assessment. The risk of developing generalised anxiety or social phobia disorders at 3-4 years was reduced by 42% (p = 0.001) and 31% (p = 0.001), respectively, for a one standard deviation increase in total sleep at 12 months. No other infant sleep outcomes were associated. Maternal depression, APC and cognitions about infant sleep did not significantly moderate these relationships. Focus may need to be on total infant sleep, rather than when sleep is achieved.

In this Age of the Anthropocene, the world of work is being radically disrupted by mass precarity, rising wage and income inequality, habitat destruction, and the rise of artificial intelligence. Facing such insecurity, people, we show, are careering toward radical ways of making a living. They range from radical professionals to social media influencing and environmental activism. Human security is fundamentally enhanced by sustainable livelihoods, and we explore ways not only to de-radicalise, but also to accept and embrace radical careering, if and whenever it serves the purpose of making people's livelihoods more sustainable for society, economies, and ecosystems. The article concludes by introducing an Index of Sustainable Livelihoods (SL-I). Success to the successful. The Sustainable Livelihoods Index (SL-I) is designed to be a 'visible hand' for end-users, including career counsellors, students, and workers undergoing career transitions, by Corporate Responsibility Officers, and by government ministries supporting just workforce transitions into sustainable livelihoods.

College students' mental health concerns have dramatically increased in prevalence and severity over the past decade, overwhelming the capacity of counseling centers to meet demand for services. In response, institutions of higher education (IHEs) increasingly emphasize prevention, education, and outreach efforts aimed at improving well-being. Although this focus has prompted an increase in research on student well-being, few studies have investigated the unique contributions of malleable psychosocial factors on student outcomes. This study aims to address this gap in the literature by examining the relative impact of an array of psychosocial factors--adaptive and maladaptive perfectionism, coping self-efficacy, social connectedness, perceived burdensomeness, grit, resilience, and meaning in life--on academic performance and distress and suicidality in a sample of 7505 students from 15 U.S. IHEs. Controlling for institutional selectivity and non-malleable aspects of students' identities and pre-college experiences, facets of perfectionism, grit, and emotion-focused coping self-efficacy were the psychosocial factors most strongly associated with GPA, and perceived burdensomeness, social connectedness, emotion-focused coping self-efficacy, and resilience were most strongly associated with distress and suicidality. Among non-malleable factors, race/ethnicity explained the most variance in GPA and gender identity explained the most variance in distress and suicidality. Results are discussed in light of persistent, identity-based disparities in academic achievement and suicide risk and the potential of psychosocial factors as intervention targets to improve academic performance and reduce suicide risk.

Autistic people experience more co-occurring health conditions and, on average, die younger than non-autistic people. Despite growing awareness of health inequities, autistic people still report barriers to accessing healthcare. We aimed to explore the experiences of autistic people accessing healthcare, shining a light on the complex interplay of relevant factors and to explain, at least in part, the possible reasons underling health disparities and adverse health outcomes. This is a qualitative study from an autistic research team. Data were collected from 1248 autistic adults as part of a large, mixed-methods, international survey exploring barriers to primary healthcare. This article reports the qualitative findings, following a thematic analysis. Using our exploratory findings, we then constructed a model to explain the reported experiences. Respondents reported a variety of barriers. Here, our article gives voice to their stories, in their own words. Themes included: early barriers; communication mismatch; doubt -- in oneself and from doctors; helplessness and fear; and healthcare avoidance and serious adverse health outcomes. Our constructed model outlines a chronological journey through which healthcare access barriers may lead to adverse health outcomes. Our findings also build on the double empathy problem, situating this in a medical context, proposing a triple empathy problem.

Background: During the COVID-19 pandemic in the United Kingdom, many health services were withdrawn from people with learning disabilities, with negative impacts on people's health. What has happened to people's health and healthcare as we move beyond the pandemic? Methods: Access to health services and health status were tracked for 550 UK adults with learning disabilities, using structured online interviews with people with learning disabilities and online surveys with family members or paid careers. Information was provided four times, from Wave 1 (in the winter 2020/2021 'lockdown') to Wave 4 (autumn 2022, over a year after public health protections stopped). Findings: By Wave 4, most people with learning disabilities had had COVID-19, although high vaccination rates limited the number of people hospitalised. There was little evidence that use of GP services, community nurses, other therapists or annual health checks had increased over time, and at Wave 4 more people were having difficulty getting their medicines. People's health did not substantially improve over time. People with profound and multiple learning disabilities had poorer health and were less likely to be accessing health services. Conclusions: Improvements in access to health services for people with learning disabilities after the pandemic have not yet happened.

New Zealand National Party's 2022-2023 policy of Social Investment, which if adopted, will legitimise the management of young unemployed in the name of correcting and helping them. Zygmunt Bauman's (1989) concept of 'rational bureaucratic culture' is used to examine the aims to bring the 'abnormal' citizen into the tax-paying fold. The policy will 'manage and make productive' young welfare recipients to avoid them 'bludging' and encourage them into 'productive work', no matter how menial. Using philanthropic monies alongside funding through Vote : Social Development is a new development which removes the state's sole financing of its safety-net responsibility. It will see a new interpretation of Principal: Agency policy.

Background: Little is known about how health issues identified at the annual health check (AHC) are followed up and addressed, how participants self-manage their health in between AHCs, and what support they receive. This research aimed to explore this. Methods: People with intellectual disabilities (n = 12), and/or their supporters residing in Wales, were interviewed following their AHC and again at 6 and 11 months. A recurrent cross-sectional thematic analysis was undertaken. Results: Five main themes emerged from interview one: going for a health check, issues identified, and actions taken, supporting the self-management of health, the personal context, and addressing health inequities. Four main themes emerged from follow-up interviews: follow-up, supporting the self-management of health, the need for reasonably adjusted health services, and going for another health check. Conclusion: A broader system of support around the AHC is required if people are to achieve or maintain the best possible health.

There has been increasing interest in the effects of note taking in second language (L2) research. However, no meta-analysis has been conducted to examine the relationship between note taking and learning through exposure to L2 input. We retrieved 28 effect sizes from 21 studies (N = 1992) to explore the overall effects of note taking as well as to examine the extent to which the effectiveness of note taking is likely to vary as a function of a set of potential moderators (i.e., learner variables, treatment variables, note-taking features, learning target, and measurement type). Results revealed that note taking had a small to medium positive overall effect on learning through exposure to L2 input (g = 0.56, 95% CI: 0.24-0.88). Subsequent moderator analyses revealed that variability in the size of note-taking effects across studies was explained by learner variables (context, region, orthographic scripts, institutional level), treatment variables (mode of input, material type), note-taking features (note-taking behavior, number of note-taking sessions, provision and type of note-taking strategy instruction, total length of instruction, opportunity to review notes), learning target, and measurement type. Based on the obtained findings, teachers are recommended to incorporate note taking in L2 classrooms. Pedagogical suggestions and directions for future research are also provided.

Policies aiming to preserve vegetated coastal ecosystems (VCE) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here the authors assessed organic carbon storage in VCE across Australian and the potential annual CO2 emission benefits of VCE conservation and find that Australia contributes substantially the carbon stored in VCE globally.

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

This paper examines how Estonian and foreign tourists to Saaremaa Island perceive their future experiences in light of a bridge built from mainland Estonia to the island. A logistic regression resulted in six predictors (two demographic and four sense of place scales) of perceived future effects of a proposed bridge on future experience, accounting for 18% of the variance. The six predictors of perceived effects of a potential bridge to the mainland on future holiday experience to Saaremaa Island were nationality, education, socio-cultural context, memory, aesthetics, and wellbeing sense of place scales. Estonians were more positive about the bridge, which supports previous discussions of the essence of home and wellbeing. Wellbeing was the strongest and only positive predictor followed by educational level, memory, socio-cultural context, aesthetics, and nationality, which were all negative. Highlights allude to the predictive power of sense of place on perceived environmental change of development (bridge to island) to future experience among tourists.

This paper describes a process of assessment reform designed to enhance Work Integrated Learning (WIL) approaches for two science courses at an Australian university. The project used a mixed-method approach involving online surveys, interviews, focus groups and workshops to gather student, industry and course team knowledge and understanding of WIL approaches to curricula. The investigation centred on the perceived value of collaborating with industry to facilitate enhancements in authentic assessment and on the barriers to, and challenges in, achieving successful outcomes. The action-research project, WIL-on-Campus (WoC), found that assessments oriented toward the inclusion of authentic tasks and processes, that contribute to the employability learning and job-readiness of students, is deemed important to students, industry and academics. However, reforms to assessment practice and process are required. For greatest impact, this study found that assessment reform processes require two critical interdependent factors: the socialisation of the shared institutional value of embedded WIL approaches to assessment, and the provision of top-down support to enable academic course teams to implement the ‘imposed’ changes. Further to this, while academics viewed the changes in approach to assessment design as challenging, they also noted that a shift is timely and believed that a course-wide WIL approach is possible and advantageous.

A subset of esophageal squamous cell carcinoma harbors dysregulated Fbxo4- cyclin D1 axis. Here, the authors show that the dysregulation of Fbxo4-cyclin D1 leads to mitochondrial dysfunction and glutamine addiction rendering these tumors susceptible to metabolic inhibitors even when resistant to CDK4/6 inhibitors.

Abstract Background Health system expenditure on cancer drugs is rising rapidly in many OECD countries given the costly new treatments and increased rates of use due to a growing and ageing population. These factors put considerable strain on the sustainability of health systems worldwide, sparking public debate among clinicians, pharmaceutical companies, policy-makers and citizens on issues of affordability and equity. We engaged Canadians through a series of deliberative public engagement events to determine their priorities for making cancer drug funding decisions fair and sustainable in Canada’s publicly financed health system. Methods An approach to deliberation was developed based on the McMaster Health Forum’s citizen panels and the established Burgess and O'Doherty model of deliberative public engagement. Six deliberations were held across Canada in 2016. Transcripts were coded in NVivo and analysed to determine where participants’ views converged and diverged. Recommendations were grouped thematically. Results A total of 115 Canadians participated in the deliberative events and developed 86 recommendations. Recommendations included the review and regular re-review of approved drugs using ‘real-world’ evidence on effectiveness and cost-effectiveness; prioritisation of treatments that restore patients’ independence, mental health and general well-being; ensuring that decision processes, results and their rationales are transparent; and commitment to people with similar needs receiving the same care regardless of where in Canada they live. Conclusions The next steps for policy-makers should be to develop mechanisms for (1) re-reviewing effectiveness and cost-effectiveness data for all cancer drugs; (2) making disinvestments in cancer drugs that satisfy requirements relating to grandfathering and compassionate access; (3) ensuring fair and equitable access to cancer drugs for all Canadians; and (4) fostering a pan-Canadian approach to cancer drug funding decisions.

Chimeric antigen receptor (CAR) T cell therapy is an innovative immunotherapy for treating cancers in both children and adults with proven utility in numerous clinical trials. Significantly, some CAR T cell therapies have now been approved by relevant national regulatory bodies across numerous countries for clinical therapeutic use outside of clinical trials. One such recently licensed product is tisagenlecleucel, a CAR T therapy approved for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) using autologous T cells from the patient. The genetically engineered T cells target a protein called CD19, common to B cells, through a CAR incorporating a 4-1BB costimulatory domain to improve response. Since tisagenlecleucel is now a standard of care treatment for B-ALL, it is clinically essential to be able to accurately monitor these CAR T cells in patients. Assessment of the copy number variant (CNV) of the CAR T cell products allows this within a clinically acceptable timeframe for optimal patient benefit. However, no standardized method with high reproducibility and efficiency has been described within a routine clinical laboratory setting. Here, we demonstrated a novel digital droplet PCR (ddPCR)-based methodology for the study of CNV (ddPCR-CNV) in 4-1BB CD19-specific CAR T cells with universal applicability across clinical diagnostic laboratories.

Venus, lacking an intrinsic global dipole magnetic field, serves as a textbook example of an induced magnetosphere, formed by interplanetary magnetic fields (IMF) enveloping the planet. Yet, various aspects of its magnetospheric dynamics and planetary ion outflows are complex and not well understood. Here we analyze plasma and magnetic field data acquired during the fourth Venus flyby of the Parker Solar Probe (PSP) mission and show evidence for closed topology in the nightside and downstream portion of the Venus magnetosphere (i.e., the magnetotail). The formation of the closed topology involves magnetic reconnection-a process rarely observed at non-magnetized planets. In addition, our study provides an evidence linking the cold Venusian ion flow in the magnetotail directly to magnetic connectivity to the ionosphere, akin to observations at Mars. These findings not only help the understanding of the complex ion flow patterns at Venus but also suggest that magnetic topology is one piece of key information for resolving ion escape mechanisms and thus the atmospheric evolution across various planetary environments and exoplanets.

BACKGROUND: Assessment of eating disorders (ED) in youth relies heavily on self-report, yet persistent lack of recognition of the presence and/or seriousness of symptoms can be intrinsic to ED. This study examines the psychometric properties of a semi-structured interview, the parent version of the Eating Disorder Examination (PEDE), developed to systematically assess caregiver report of symptoms. METHODS: A multi-site, clinical sample of youth (N = 522; age range: 12 to 18 years) seeking treatment for anorexia nervosa (AN) and subsyndromal AN were assessed using the Eating Disorder Examination (EDE) for youth and the PEDE for collateral caregiver report. RESULTS: Internal consistencies of the four PEDE subscales were on par with established ranges for the EDE. Significant medium-sized correlations and poor to moderate levels of agreement were found between the corresponding subscales on each measure. For the PEDE, confirmatory factor analysis of the EDE four-factor model provided a poor fit; an exploratory factor analysis indicated that a 3-factor model better fits the PEDE. CONCLUSIONS: Findings suggest that the PEDE has psychometric properties on par with the original EDE. The addition of the caregiver perspective may provide incremental information that can aid in the assessment of AN in youth. Future research is warranted to establish psychometric properties of the PEDE in broader transdiagnostic ED samples.

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Increasing survival rates of children following cancer treatment have resulted in a significant population of adult survivors with the common side effect of infertility. Additionally, the availability of genetic testing has identified Klinefelter syndrome (classic 47,XXY) as the cause of future male infertility for a significant number of prepubertal patients. This study explores new spermatogonia stem cell (SSC)-based fertility therapies to meet the needs of these patients. Testicular cells were isolated from cryopreserved human testes tissue stored from XY and XXY prepubertal patients and propagated in a two-dimensional culture. Cells were then incorporated into a 3D human testicular organoid (HTO) system. During a 3-week culture period, HTOs maintained their structure, viability, and metabolic activity. Cell-specific PCR and flow cytometry markers identified undifferentiated spermatogonia, Sertoli, Leydig, and peritubular cells within the HTOs. Testosterone was produced by the HTOs both with and without hCG stimulation. Upregulation of postmeiotic germ cell markers was detected after 23 days in culture. Fluorescence in situ hybridization (FISH) of chromosomes X, Y, and 18 identified haploid cells in the in vitro differentiated HTOs. Thus, 3D HTOs were successfully generated from isolated immature human testicular cells from both euploid (XY) and Klinefelter (XXY) patients, supporting androgen production and germ cell differentiation in vitro.

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies.

BackgroundCannabis exposures reported to the California Poison Control System increased following the initiation of recreational cannabis sales on 1 January 2018 (i.e., "commercialization"). We evaluated whether local cannabis control policies adopted by 2021 were associated with shifts in harmful cannabis exposures.MethodsUsing cannabis control policies collected for all 539 California cities and counties in 2020-2021, we applied a differences-in-differences design with negative binomial regression to test the association of policies with harmful cannabis exposures reported to California Poison Control System (2011-2020), before and after commercialization. We considered three policy categories: bans on storefront recreational retail cannabis businesses, overall restrictiveness, and specific recommended provisions (restricting product types or potency, packaging and labeling restrictions, and server training requirements).ResultsLocalities that ultimately banned storefront recreational retail cannabis businesses had fewer harmful cannabis exposures for children aged 13 years (rate ratio = 0.97; 95% confidence interval = 0.85, 1.11). Of 167 localities ultimately permitting recreational cannabis sales, overall restrictiveness was not associated with harmful cannabis exposures among children aged 13 years, a 1-standard deviation increase in ultimate restrictiveness was associated with fewer harmful cannabis exposures (rate ratio = 0.93; 95% confidence interval = 0.86, 1.01). For recommended provisions, estimates were generally too imprecise to detect associations with harmful cannabis exposures.ConclusionBans on storefront retail and other restrictive approaches to regulating recreational cannabis may be associated with fewer harmful cannabis exposures for some age groups following statewide commercialization.

Accurate dynamic object manipulation in a robotic hand remains a difficult task, especially when frictional slip is involved. Prior solutions involve extensive data collection to train complex models to control the hand that do not necessarily generalize to other slip circumstances. Our approach focuses on direct slip sensing using a tactile sensor with a capacitive array, coupled with a programmable system on a chip, capable of mode switching and sampling rate adjustment. We characterize the sensor's capacity to sense slip features at higher speeds and introduce a novel methodology for estimating motions. Low-level sensor reprogramming that couples multiple taxels improves slip avoidance and reaction time during rapid slip onset events. The technology also tracks dominant surface vibration frequencies resulting from stick-slip cycles, estimating speed and acceleration of smooth flat surfaces. Using a parallel-jaw robotic gripper, we demonstrate dynamic repositioning of objects lacking trackable surface features within the hand. The goal of this investigation is to support faster reasoning and reflexes for dynamic dexterous robots that experience directional in-hand slip.

The cellular components of tumors and their microenvironment play pivotal roles in tumor progression, patient survival, and the response to cancer treatments. Unveiling a comprehensive cellular profile within bulk tumors via single-cell RNA sequencing (scRNA-seq) data is crucial, as it unveils intrinsic tumor cellular traits that elude identification through conventional cancer subtyping methods. Our contribution, scBeacon, is a tool that derives cell-type signatures by integrating and clustering multiple scRNA-seq datasets to extract signatures for deconvolving unrelated tumor datasets on bulk samples. Through the employment of scBeacon on the The Cancer Genome Atlas (TCGA) cohort, we find cellular and molecular attributes within specific tumor categories, many with patient outcome relevance. We developed a tumor cell-type map to visually depict the relationships among TCGA samples based on the cell-type inferences.

Welcome to the 25th anniversary edition of PLEXUS, UC Irvine School of Medicine’s annual student-organized Journal of Medical Humanities & Arts. To mark this celebratory milestone, it is with great pleasure that I present to you NAVIGATE. In the ever-evolving landscape of medicine, the ability to navigate through challenges and unforeseen obstacles is paramount. NAVIGATE serves as a timely invitation for our colleagues to reflect on the distances traversed and to envision the new horizons that lie ahead. We sought to highlight the constellation of tools utilized when we feel lost and to acknowledge the beacons that steer our actions. The subsequent pages offer its readers profoundinsights into the extraordinary journeys undertaken by the greater UCI Health community. We hope it delivers a sense of direction, solace, and clarity to all readers.As we celebrate our 25th anniversary, wehonor the visionaries, contributors, and readers that have propelled us forward on this remarkable voyage. Their collective support fuels our efforts to serve as a creative outlet for the community, catalyze meaningful discussions, and apply the tenets of medical humanities to foster a cohort of compassionate healers.We extend our deepest gratitude to our faculty advisors Dr. Juliet McMullin and Dr. TanNguyen for their invaluable guidance and for sharing their expertise within the field. We thank the UCISOM Medical Humanities & Arts Program and the UCI Department of Family Medicine for their unwavering support. I invite you to embark on this exploration with us, and witness the intricate tapestry of our contributors’ lived experiences that defines our shared journey in healthcare.Bon voyage,Christopher SahagianEditor-in-ChiefCreative Review — Caroline GeeCreative Review — Huan NguyenCreative Review — Sana ShahDesign — Nicole ParkerDesign — Britney WengFaculty Advisor — Dr. Juliet McMullinFaculty Advisor — Dr. Tan NguyenStaff Advisor — Leonora Naser-Saravia{Front Cover): NEW HEIGHTS Britney Weng, MS1San Pedro de Atacama, Chile(Inner Cover): TRAVERSING  Britney Weng, MS1Chile Route 23