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Abstract AKL-T01 is a digital therapeutic (DTx) that targets attention by generating conflict at dynamically updated difficulty levels during a multitasking game. Clinical trials support AKL-T01’s efficacy in attention-deficit/hyperactivity disorder (ADHD), but there is a need to understand how in-game data can be used to monitor patient changes in cognition. We aimed to derive a real-time measure of attention from AKL-T01 gameplay data and validate it against clinical outcomes. Trials of AKL-T01 included: STARS-ADHD-Adult (NCT05183919), a 6-week trial in adults 18 and older (n = 221; M age = 39.9; 70% female); STARS-ADHD-Adolescent (NCT04897074), a 4-week trial in adolescents ages 13–17 (n = 162; M age = 14.4; 41% female); and STARS-ADHD (NCT02674633), a 4-week trial in children ages 8–12 (n = 180; M age = 9.7; 31% female). A cognitive metric was derived from targeting response speed, targeting sensitivity (d-prime), and navigation skill level. Using multiple linear regression models, we analyzed relationships between cognitive metric change and changes in the Test of Variables of Attention (TOVA)-Attention Comparison Score (ACS), controlling for TOVA-ACS baseline, cognitive metric baseline, age, and sex. We explored associations with ADHD symptoms and quality of life. Increases in the cognitive metric significantly predicted increases in TOVA-ACS in the adult (β = 0.16, p

Background As graph datasets—including social networks, supply chains, and bioinformatics data—grow in size and complexity, researchers are driven to search for solutions enhancing model efficiency and speed. One avenue that may provide a solution is Quantum Graph Learning (QGL), a subfield of Quantum Machine Learning (QML) that applies machine learning inspired or powered by quantum computing to graph learning tasks. Methods We reevaluate Quantum Feature Embeddings (QFE), a QGL methodology published by Xu et al. earlier this year. QFE uses Variational Quantum Circuits to preprocess node features and then sends them to a classical Graph Neural Network (GNN), with the goal of increasing performance and/or decreasing total model size. Xu et al. evaluated this methodology by comparing its performance with the performance of variously-sized classical models on the benchmark datasets PROTEINS and ENZYMES, and they report success. Our core methodology and learning task remain unchanged. However, we have made several changes to the experimental design that enhance the rigor of the study: 1) we include the testing of models with no embedder; 2) we conduct a thorough hyperparameter search using a state-of-the-art optimization algorithm; and 3) we conduct stratified five-fold cross-validation, which mitigates the bias produced by our small datasets and provides multiple test statistics from which we can calculate a confidence interval. Results We produce classical models that perform comparably to QFE and significantly outperform the small classical models used in Xu et al.’s comparison. Notably, many of our classical models achieve this using fewer parameters than the QFE models we trained. Xu et al. do not report their total model sizes. Conclusion Our study sheds doubt on the efficacy of QFE by demonstrating that small, well-tuned classical models can perform just as well as QFE, highlighting the importance of hyperparameter tuning and rigorous experimental design.

This article aims to explore the evolution of the debates surrounding human rights in the discourse(s) of major sporting events (MSEs), particularly the Olympics. The paper will first analyse the western-centric origins of the “universality” of the Olympic philosophy and how it affected the protection and promotion of human rights, as well as addressing practical challenges or limitations faced. It will then focus on unpacking the elements of sportswashing and soft power in the multi-discursive context of sport where power, privilege, politics, and position are (re)produced. In doing so it draws upon the emergent field of Sports Diplomacy as the most appropriate explanatory framework to share in this discourse. Finally, it will explore the potential impact of anti-corruption reforms on the establishment of a meaningful human rights legacy.

Abstract Background Forcibly displaced populations are highly vulnerable to psychosocial distress and mental disorders, including alcohol misuse. In an ongoing trial that seeks to develop a transdiagnostic intervention addressing psychological distress and alcohol use disorders among conflict-affected populations, we will carry out a cost-effectiveness evaluation using a capability-based Oxford Capabilities Mental Health (OxCAP-MH) measure. The OxCAP-MH is a 16-item questionnaire developed from the Capability Approach, that covers multiple domains of functioning and welfare. The aim of the current paper is to present the results of the translation, cultural adaptation and valuation of the OxCAP-MH into Juba Arabic for South Sudanese refugees living in Uganda. We adhered to the official Translation and Linguistic Validation process of the OxCAP-MH. To carry out the translation, the Concept Elaboration document, official English version of the OxCAP-MH, and the Back-Translation Review Template were used. Four independent translators were used for forward and back translations. The reconciled translated version was then piloted in two focus group discussions (N = 16) in Rhino refugee settlement. A most important to least important valuation of the sixteen capability domains covered in the OxCAP-MH was also done. Results The Juba Arabic version of the OxCAP-MH was finalized following a systematic iterative process. The content of the Juba Arabic version remained unchanged, but key concepts were adapted to ensure cultural acceptability, feasibility, and comprehension of the measure in the local context of Rhino refugee settlement. Most participants had low levels of literacy and required support with filling in the tool. Participants suggested an additional capability that is currently not reflected in the OxCAP-MH, namely access to food. Furthermore, discussions around the valuation exercise of the sixteen domains led to two separate importance scales, which showed relevant differences. Conclusions In this context, the OxCAP-MH was considered culturally acceptable. The valuation exercise proved cognitively demanding. Participants voiced confusion over how to answer the questions on the OxCAP-MH instrument due to low levels of literacy. These concerns invite consideration for future research to consider how measures such as the OxCAP-MH can be made more accessible to individuals with low literacy rates in resource poor settings.

Robotic surgery is emerging as a feasible minimally invasive approach for donor hepatectomy at specialized centers. The aim of this article is to systematically describe the surgical techniques for robotic parenchymal transection and bile duct division in right donor hepatectomy. The setup of the robotic arms, methods of parenchymal transection using robotic instruments, and right hepatic duct division with the aid of indocyanine green dye are detailed, along with the pearls and pitfalls of these two parts of the operation.

Robotic surgery is emerging as a feasible minimally invasive approach for donor hepatectomy at specialized centers. The aim of this article is to systematically describe the surgical techniques for robotic hilar dissection and right lobe mobilization in right donor hepatectomy. The setup of the robotic arms, the dissection of inflow vessels and retrohepatic inferior vena cava, and the pearls and pitfalls of these two parts of the operation are detailed.

Abstract Neutrophils are one of the first responders to infection and are a key component of the innate immune system through their ability to phagocytose and kill invading pathogens, secrete antimicrobial molecules and produce extracellular traps. Neutrophils are produced in the bone marrow, circulate within the blood and upon immune challenge migrate to the site of infection. We wanted to understand whether this transition shapes the mouse neutrophil protein landscape, how the mouse neutrophil proteome is impacted by systemic infection and perform a comparative analysis of human and mouse neutrophils. Using quantitative mass spectrometry we reveal tissue-specific, infection-induced and species-specific neutrophil protein signatures. We show a high degree of proteomic conservation between mouse bone marrow, blood and peritoneal neutrophils, but also identify key differences in the molecules that these cells express for sensing and responding to their environment. Systemic infection triggers a change in the bone marrow neutrophil population with considerable impact on the core machinery for protein synthesis and DNA replication along with environmental sensors. We also reveal profound differences in mouse and human blood neutrophils, particularly their granule contents. Our proteomics data provides a valuable resource for understanding neutrophil function and phenotypes across species and model systems.

Abstract Introduction Clinical practice guidelines recommend against the routine use of psychotropic medications in residential aged care facilities (RACFs). Knowledge brokers are individuals or groups who facilitate the transfer of knowledge into practice. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of using knowledge brokers to translate Australia’s new Clinical Practice Guidelines for the Appropriate Use of Psychotropic Medications in People Living with Dementia and in Residential Aged Care. Methods and analysis The Evidence-based Medication knowledge Brokers in Residential Aged CarE (EMBRACE) trial is a helix-counterbalanced randomised controlled trial. The 12-month trial will be conducted in up to 19 RACFs operated by four Australian aged care provider organisations in Victoria, New South Wales, Western Australia and Queensland. RACFs will be randomised to receive three levels of implementation strategies (knowledge broker service, pharmacist-led quality use of medications education activities and distribution of the Guidelines and supporting materials) across three medication contexts (antipsychotics, benzodiazepines and antidepressants). Implementation strategies will be delivered by an embedded on-site aged care pharmacist working at a system level across each participating RACF. All RACFs will receive all implementation strategies simultaneously but for different medication contexts. The primary outcome will be a composite dichotomous measure of 6-month RACF-level concordance with Guideline recommendations and good practice statements among people using antipsychotics, benzodiazepines and antidepressants for changed behaviours. Secondary outcomes will include proportion of residents with Guideline concordant use of antipsychotics, benzodiazepines and antidepressants measured at the RACF-level and proportion of residents with psychotropic medication use, hospitalisation, falls, falls with injury, polypharmacy, quality of life, activities of daily living, medication incidents and behavioural incidents measured at the RACF-level. Discussion The EMBRACE trial investigates a novel guideline implementation strategy to improve the safe and effective use of psychotropic medications in RACFs. We anticipate that the findings will provide new information on the potential role of knowledge brokers for successful and cost-effective guideline implementation. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623001141639. Registered 6 November 2023 — retrospectively registered, https://www.anzctr.org.au/TrialSearch.aspx .

Baleen whales are key consumers in marine ecosystems and can serve as ecosystem sentinels. Body condition, defined as an individual’s energy stores relative to its structural size, can provide a useful proxy for health in baleen whales. As capital breeders, important life history events in baleen whales such as seasonal migrations and reproduction depend on having sufficient energy stores. Spatiotemporal variability of body condition of baleen whales can reflect differences in energy accumulated during the foraging season. Here we assess and compare the body condition and mass of humpback whales (Megaptera novaeangliae) across four different foraging areas from the West Indies distinct population segment in the Northwest Atlantic. Morphometric measurements of humpback whales were obtained using unoccupied aerial systems (UAS, or drones) from the New York Bight, the Gulf of Maine, Iceland, and Greenland. Uncertainty in morphometric estimates was incorporated and propagated using a bootstrapping approach. Measurements were used to estimate body volume and calculate a body condition index (BCI) for each individual whale. Since body mass is a key parameter for understanding animal physiology and bioenergetics, we further compared whale body mass to body size between foraging areas by converting body volume to body mass using estimates of tissue density from tagging studies. BCI showed significant differences between foraging areas with a large effect size (ANCOVA: mean η2 = 0.168; all p< 0.001) when incorporating day of year and year as covariates. Humpback whales in the Gulf of Maine showed significantly higher BCI than those in the New York Bight, Iceland, and Greenland. Standardized Major Axis (SMA) regressions comparing log-log relationships of both body volume and body mass, respectively, to total length reinforced these results. Humpback whales in the Gulf of Maine showed significantly higher elevation in the SMAs than those in the other study regions (p

Abstract Earth system models currently struggle to account for the complex effects that land surface heterogeneity can have on land‐atmosphere interactions. There have been attempts to include the impact of this heterogeneity on the atmosphere, but they ignore the development of coherent circulations that can be driven by spatial differential surface heating. A wealth of literature, particularly large‐eddy simulation (LES) based studies, shows that these circulations have significant impacts on the development and organization of clouds. In this work, we describe a two‐column model with a parameterized circulation driven by atmospheric virtual potential temperature profiles, differences in near surface temperature between the two columns, patterns of surface heterogeneity, and the mean background wind. Key aspects of the proposed model structure are compared with LES output, and the model is then implemented between two otherwise independent single column models. While some avenues for improvement exist, when the circulations are parameterized, we see increased cloud development and realistic changes to the mean profiles of temperature and moisture. The proposed model qualitatively matches expectations from the literature and LES, and points to the potential success of its future implementation in coarse grid models.

Abstract Objective To investigate the trends in antiseizure medications (ASMs) use following ischemic stroke and to examine factors associated with use of newer‐ and older‐generation ASMs. Methods A retrospective cohort study was conducted using state‐wide linked health datasets. Patients who were hospitalized with a first‐ever ischemic stroke between 2013 and 2017 and were dispensed ASM within 12 months from discharge were included. Logistic regression was used to examine the predictors of receiving newer‐generation ASMs. Generalized linear modeling was used to identify factors associated with ASM use after ischemic stroke. Results Of 19 601 people hospitalized with a first‐ever ischemic stroke, 989 were dispensed an ASM within 12 months from discharge. The most prevalent first ASMs were levetiracetam (38.0%), valproate (25.8%), and carbamazepine (10.3%). Most people were dispensed ASM monotherapy (86.9%). There was a shift toward the use of newer‐generation ASMs between 2013 and 2017 (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.92–4.16). Metropolitan residents were more likely to be dispensed newer‐generation ASMs as a first‐line treatment (OR 1.79, 95% CI 1.31–2.45). People over 85 years (OR 0.38, 95% CI 0.23–0.64), with dementia (OR 0.35, 95% CI 0.19–0.63) and psychotic comorbidities (OR 0.29, 95% CI 0.09–0.96) were less likely to be dispensed newer‐generation ASMs. Older age (coefficient [β] 0.23, P = 0.030), history of beta blocker use (β 0.17, P = 0.029), multiple ASMs (β 0.78, P

Abstract Background We investigated the association between post‐hospital discharge use of sodium glucose cotransporter‐2 inhibitors (SGLT‐2is) compared to dipeptidyl peptidase‐4 inhibitors (DPP‐4is) and the incidence of hospitalization for acute renal failure (ARF) and chronic kidney disease (CKD) in people with type 2 diabetes. Methods We conducted a retrospective cohort study using linked hospital and prescription data. Our cohort included people aged ≥30 years with type 2 diabetes discharged from a hospital in Victoria, Australia, from December 2013 to June 2018. We compared new users of SGLT‐2is with new users of DPP‐4is following discharge. People were followed from first dispensing of a SGLT‐2i or DPP‐4i to a subsequent hospital admission for ARF or CKD. We used competing risk models with inverse probability of treatment weighting (IPTW) to estimate subhazard ratios. Results In total, 9620 people initiated SGLT‐2is and 9962 initiated DPP‐4is. The incidence rate of ARF was 12.3 per 1000 person‐years (median years of follow‐up [interquartile range [IQR] 1.4 [0.7–2.2]) among SGLT‐2i initiators and 18.9 per 1000 person‐years (median years of follow‐up [IQR] 1.7 [0.8–2.6]) among DPP‐4i initiators (adjusted subhazard ratio with IPTW 0.78; 95% confidence interval [CI] 0.70–0.86). The incidence rate of CKD was 6.0 per 1000 person‐years (median years of follow‐up [IQR] 1.4 [0.7–2.2]) among SGLT‐2i initiators and 8.9 per 1000 person‐years (median years of follow‐up [IQR] 1.7 [0.8–2.6]) among DPP‐4i initiators (adjusted subhazard ratio with IPTW 0.83; 95% CI 0.73–0.94). Conclusions Real‐world data support using SGLT‐2is over DPP‐4is for preventing acute and chronic renal events in people with type 2 diabetes.

Background. The COVID-19 pandemic has led to an increase in SARS-CoV-2–test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19–positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19–positive donors at a single center are presented here. Methods. A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19–positive (n = 29 total; 25 index, 4 redo) and COVID-19–negative (n = 472 total; 454 index, 18 redo) deceased donor liver grafts were compared. Results. COVID-19–positive donors were significantly younger (P = 0.04) and had lower kidney donor profile indices (P = 0.04) than COVID-19–negative donors. Recipients of COVID-19–positive donor grafts were older (P = 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; P = 0.89). There were 3 deaths among recipients of liver grafts from COVID-19–positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants. Conclusions. The utilization of liver grafts from COVID-19–positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19–positive donors may be used safely to expand the deceased donor pool.

Summary: Inflammation is closely associated with many neurodegenerative disorders. Yet, whether inflammation causes, exacerbates, or responds to neurodegeneration has been challenging to define because the two processes are so closely linked. Here, we disentangle inflammation from the axon damage it causes by individually blocking cytotoxic T cell function and axon degeneration. We model inflammatory damage in mouse skin, a barrier tissue that, despite frequent inflammation, must maintain proper functioning of a dense array of axon terminals. We show that sympathetic axons modulate skin inflammation through release of norepinephrine, which suppresses activation of γδ T cells via the β2 adrenergic receptor. Strong inflammatory stimulation—modeled by application of the Toll-like receptor 7 agonist imiquimod—causes progressive γδ T cell-mediated, Sarm1-dependent loss of these immunosuppressive sympathetic axons. This removes a physiological brake on T cells, initiating a positive feedback loop of enhanced inflammation and further axon damage.

Abstract Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling. The structures of homodimeric PAPP-A in complex with IGFBP5 anchor peptide, and inhibitor proteins STC2 and proMBP have been recently reported. Here, we present the single-particle cryo-EM structure of the monomeric, N-terminal LG, MP, and the M1 domains (with the exception of LNR1/2) of human PAPP-A2 to 3.13 Å resolution. Our structure together with functional studies provides insight into a previously reported patient mutation that inactivates PAPP-A2 in a distal region of the protein. Using a combinational approach, we suggest that PAPP-A2 recognizes IGFBP5 in a similar manner as PAPP-A and show that PAPP-A2 cleaves IGFBP5 less efficiently due to differences in the M2 domain. Overall, our studies characterize the cleavage mechanism of IGFBP5 by PAPP-A2 and shed light onto key differences with its paralog PAPP-A.

Abstract The global food system is facing the challenge of producing sufficient nutrients to accommodate future demands within planetary boundaries, while reducing malnutrition. Although nutrient-rich seafood can play a prominent role in resolving this challenge, seafood from capture fisheries is currently partly wasted. Here we quantified the nutrient contribution from capture fisheries through a hypothetical scenario that assumed all captured seafood and byproducts from seafood processing would be used for human consumption. Our simulations show that available seafood per capita can be doubled without increasing the pressure on global fisheries when all reported, illegal, and discarded capture is used as food, complemented with processing byproducts. In such a scenario, seafood contributes greatly to daily nutrient requirements – e.g., omega-3 can be fully met. Although uncertainty should be considered, these results indicate that putting the whole fish on the table can increase nutrient availability from capture fisheries substantially and sustainably.

Abstract The memorialization of mass atrocities such as war crimes and genocides facilitates the remembrance of past suffering, honors those who resisted the perpetrators, and helps prevent the distortion of historical facts. Digital technologies have transformed memorialization practices by enabling less top-down and more creative approaches to remember mass atrocities. At the same time, they may also facilitate the spread of denialism and distortion, attempt to justify past crimes and attack the dignity of victims. The emergence of generative forms of artificial intelligence (AI), which produce textual and visual content, has the potential to revolutionize the field of memorialization even further. AI can identify patterns in training data to create new narratives for representing and interpreting mass atrocities—and do so in a fraction of the time it takes for humans. The use of generative AI in this context raises numerous questions: For example, can the paucity of training data on mass atrocities distort how AI interprets some atrocity-related inquiries? How important is the ability to differentiate between human- and AI-made content concerning mass atrocities? Can AI-made content be used to promote false information concerning atrocities? This article addresses these and other questions by examining the opportunities and risks associated with using generative AIs for memorializing mass atrocities. It also discusses recommendations for AIs integration in memorialization practices to steer the use of these technologies toward a more ethical and sustainable direction.

O antigo problema das marés, fenômeno observado desde os primórdios da humanidade, ainda nos lega análises importantes. Nesse trabalho, a partir do estudo desse fenômeno, mas levando em conta a gravitação, determinamos características da Lua, tais como como a massa, volume e aspectos da composição química. Essa determinação é feita usando um tipo de método inverso, proposto por Henrique Fleming. Essa abordagem nos permite reexaminar a análise qualitativa de Galilei sobre o problema, partindo exclusivamente dos movimentos da Terra. Apontamos para a importância da formulação galileana, criticada em certos estudos.