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Abstract Positron emission tomography (PET) imaging of neurodegenerative disease has historically focused on a small number of established targets. The development of selective PET radiotracers for novel biological targets enables new ways to interrogate the neuropathology of proteinopathies and will advance our understanding of neurodegeneration. This perspective aims to highlight recent PET radiotracers developed for five emerging targets in proteinopathies (i.e., mHTT, BACE1, TDP-43, OGA, and CH24H).

Purpose: Business model (BM) canvases have been used in educational institutions and business incubators for over a decade to assist students and start-up entrepreneurs in developing their business projects. Given the urgency of tackling sustainability challenges, several tools have emerged to stimulate sustainable business modeling (SBM). However, these tools are often too complex for nonexperts in business modeling or sustainability, and thus insufficiently user-friendly for educational contexts. This study aims to address this pedagogical gap by describing the design process of the responsible business model canvas (RBMC). Design/methodology/approach: The authors relied on a design science research methodology involving the active participation of end users, entrepreneurship educators, business coaches and external partners. The authors proposed four criteria and ten subcriteria to analyze existing SBM canvases based on their user-friendliness and to design the initial prototype of the RBMC. The RBMC was subsequently tested in various settings, including classroom assignments and business incubation programs, with over 1,000 university students. The tool was refined and assessed throughout the development process, incorporating feedback from focus groups with start-up entrepreneurs. Findings: Through the development process, the authors created a user-friendly tool to help novice student and start-up entrepreneurs integrate sustainability into their BMs: the RBMC. The canvas consists of 14 building blocks grouped into four areas: consistency ("mission, vision, values"), desirability ("value propositions, customer segments, users and beneficiaries, customer relationships" and "channels"), feasibility ("key activities, key resources, key partners and stakeholders" and "governance") and viability ("cost structure, revenues streams, negative impacts and positive impacts"). Research limitations/implications: The research methods and user-friendliness criteria in this study can be applied in other contexts to design tools to support sustainable entrepreneurship education. While the RBMC is currently being used in several educational institutions throughout the world, its impacts in different pedagogical and cultural settings require further validation. Practical implications: The RBMC is a user-friendly tool to introduce students and start-up entrepreneurs to SBM. It helps raise users' awareness about sustainability concerns, challenging them to consider issues they might have otherwise overlooked. Some participants even shifted their outlook and were motivated to develop a long-term vision integrating compensatory, mitigative or corrective actions into their BMs. Originality/value: The RBMC is the outcome of a balanced approach that combines both pragmatic (i.e. user-friendliness) and normative (i.e. sustainability) perspectives. It provides users with a systematic approach for integrating and applying sustainability issues in their business projects.

Abstract The Gulf of St. Lawrence is increasingly affected by bottom water hypoxia; however, the timescales and pathways of deep water transport remain unclear. Here, we present results from the Deep Tracer Release eXperiment (TReX Deep), during which an inert SF5CF3 tracer was released inshore of Cabot Strait at 279 m depth to investigate deep inflow transport and mixing rates. Dispersion was also assessed via neutrally-buoyant Swish floats. Our findings indicate that the tracer moves inland at 0.5 cm s−1, with an effective lateral diffusivity of 2 × 102 m2 s−1 over 1 year. Simplified 1D simulations suggest inflow water should reach the estuary head in 1.7 years, with the bulk arriving after 4.7 years. Basin-wide effective vertical diffusivity is around 10−5 m2 s−1 over 1 year; however, vertical diffusivity increases near the basin slopes, suggesting that turbulent boundary processes influence mixing. These results are compared to Lagrangian simulations in a regional 3D model to evaluate the capacity to model dispersion in the Gulf.

Abstract We aimed to implement four data partitioning strategies evaluated with four federated learning (FL) algorithms and investigate the impact of data distribution on FL model performance in detecting steatosis using B-mode US images. A private dataset (153 patients; 1530 images) and a public dataset (55 patient; 550 images) were included in this retrospective study. The datasets contained patients with metabolic dysfunction-associated fatty liver disease (MAFLD) with biopsy-proven steatosis grades and control individuals without steatosis. We employed four data partitioning strategies to simulate FL scenarios and we assessed four FL algorithms. We investigated the impact of class imbalance and the mismatch between the global and local data distributions on the learning outcome. Classification performance was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. AUCs were 0.93 (95% CI 0.92, 0.94) for source-based partitioning scenario with FedAvg, 0.90 (95% CI 0.89, 0.91) for a centralized model, and 0.83 (95% CI 0.81, 0.85) for a model trained in a single-center scenario. When data was perfectly balanced on the global level and each site had an identical data distribution, the model yielded an AUC of 0.90 (95% CI 0.88, 0.92). When each site contained data exclusively from one single class, irrespective of the global data distribution, the AUC fell in the range of 0.34–0.70. FL applied to B-mode US images provide performance comparable to a centralized model and higher than single-center scenario. Global data imbalance and local data heterogeneity influenced the learning outcome.

The Gulf of St. Lawrence (GSL), along with the St. Lawrence Estuary, is the largest estuarine system in North America. It is a biologically productive sea and an important fishing ground in Canada. The objectives of this study are to determine how climate changes will affect primary production in the GSL and on the eastern Scotian Shelf, and to determine the drivers of the changes. We use a regional ocean model forced with downscaled output of the Max-Planck Institute Earth System Model to study the changes in net primary production under the climate change scenario of Representative Concentration Pathway 8.5 (RCP8.5). Results reveal a projected 13.4% decrease in annual primary production across the GSL system over the next 70 years. This decline primarily stems from reduced nutrient concentrations in the upper layer, despite the increase in nutrients supplied by rivers. Enhanced freshwater influx and ocean surface warming contribute to heightened stratification, that in turn reduce the vertical nutrient fluxes from deeper layers. This mechanism affects the upwelling of nutrient-rich water at the head of the Laurentian Channel in the Lower St. Lawrence Estuary, leading to a 22% reduction in the vertical nitrate flux in the future. Additionally, nutrient concentrations in the water masses entering the GSL at the Strait of Belle Isle and at Cabot Strait are also reduced. Due to declining sea-ice concentration, the phytoplankton bloom is expected to occur between 9 and 23 days earlier under a warmer climate, and last for up to 24 days longer, depending on the GSL subregions, compared to the historical period (2001-2020). Biological productivity at higher trophic levels, and thus fisheries productivity, could be negatively impacted under the RCP8.5 climate change scenario.

Abstract Background Early discharge of frail older adults from post-acute care service may result in individuals’ reduced functional ability to carry out activities of daily living, and social, emotional, and psychological distress. To address these shortcomings, the Montreal West Island Integrated University Health and Social Services Centre in Quebec, Canada piloted a post-acute home physiotherapy program (PAHP) to facilitate the transition of older adults from the hospital to their home. This study aimed to evaluate: (1) the implementation fidelity of the PAHP program; (2) its impact on the functional independence, physical and mental health outcomes and quality of life of older adults who underwent this program (3) its potential adverse events, and (4) to identify the physical, psychological, and mental health care needs of older adults following their discharge at home. Methods A quasi-experimental uncontrolled design with repeated measures was conducted between April 1st, 2021 and December 31st, 2021. Implementation fidelity was assessed using three process indicators: delay between referral to and receipt of the PAHP program, frequency of PAHP interventions per week and program duration in weeks. A battery of functional outcome measures, including the Functional Independence Measure (FIM) and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 scale, as well as fall incidence, emergency visits, and hospitalizations were used to assess program impact and adverse events. The Patient’s Global Impression of Change (PGICS) was used to determine changes in participants’ perceptions of their level of improvement/deterioration. In addition, the Camberwell Assessment of Need for the Elderly (CANE) questionnaire was administered to determine the met and unmet needs of older adults. Results Twenty-four individuals (aged 60.8 to 94 years) participated in the PAHP program. Implementation fidelity was low in regards with delay between referral and receipt of the program, intensity of interventions, and total program duration. Repeated measures ANOVA revealed significant improvement in FIM scores between admission and discharge from the PAHP program and between admission and the 3-month follow-up. Participants also reported meaningful improvements in PGICS scores. However, no significant differences were observed on the physical or mental health T-scores of the PROMIS Global-10 scale, in adverse events related to the PAHP program, or in the overall unmet needs. Conclusion Findings from an initial sample undergoing a PAHP program suggest that despite a low implementation fidelity of the program, functional independence outcomes and patients’ global impression of change have improved. Results will help develop a stakeholder-driven action plan to improve this program. A future study with a larger sample size is currently being planned to evaluate the overall impact of this program. Clinical trial registration Retrospectively registered NCT05915156 (22/06/2023).

The mineralogy of niobium (Nb) is characterized by multicomponent oxides such as AB2O6, A2B2O7, ABO4, and ABO3 in which Nb is incorporated in the B site. Such complex crystal-chemistry prevents their unambiguous identification in ore deposits such as hydrothermal rocks and laterites which exhibit complex and fine-grained textures. The understanding of the processes controlling Nb ore deposit formation in various geological settings is therefore limited, although Nb is a critical element. In this study, we use X-ray absorption spectroscopy (XAS) at the Nb K-edge to investigate the local atomic-scale structure around Nb in a large set of natural and synthetic minerals of geological and technological importance. Our X-ray absorption near-edge structure (XANES) data at the Nb K-edge show three major features of variable position and intensity and then can be related to the local distortion and coordination number of the Nb site. Shell-by-shell fits of the extended X-ray absorption fine structure (EXAFS) data reveal that the NbO6 octahedra are distorted in a variety of pyrochlore species. At least two distinct first shells of O atoms are present while reported crystallographic data yield regular octahedra in the same minerals. Next-nearest Nb–Nb distances in pyrochlore and Nb-bearing perovskite mirror a corner-sharing NbO6 network, whereas the two Nb–Nb distances in columbite are typical of edge- and corner-sharing NbO6 octahedra. Such a resolution on the Nb site geometry and the intersite relationships between the next-nearest NbO6 octahedra is made possible by collecting EXAFS data under optimal conditions at 20 K and up to 16 Å−1. The local structure around substituted Nb5+ in Fe3+, Ti4+, and Ce4+ oxides suffers major changes relative to the unsubstituted structures. The substitution of Nb5+ for Ti4+ in anatase leads to the increase in the interatomic distances between Nb and its first and second Ti4+ neighbors. The substitution of Nb5+ for Ce4+ in cerianite reduces the coordination number of the cation from eight to four, and the Nb–O bonds are shortened compared to Ce–O ones. In hematite, Nb5+ occupies a regular site, whereas the Fe3+ site is strongly distorted suggesting major site relaxation due to charge mismatch. The sensitivity of XANES and EXAFS spectroscopies at the Nb K-edge to the local site geometry and next-nearest neighbors demonstrated in this study would help decipher Nb speciation and investigate mineralogical reactions of Nb minerals in deposit-related contexts such as hydrothermal and lateritic deposits.

OBJECTIVES:. Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients. DATA SOURCES:. MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. STUDY SELECTION:. Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021. DATA EXTRACTION:. Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case–control studies, and risk-of-bias framework for clinical trials. DATA SYNTHESIS:. Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1–2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89–95%, pediatric: 80–97%), SE (adults: 54–100%, pediatric: 60–100%), and DS (adults: 60–90%, pediatric: 62–90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol. CONCLUSIONS:. Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed.

Abstract Plant secondary metabolites (PSMs) can potentially reduce ruminal methane formation. However, related to differences in their molecular structures, it is not yet clear what causes an anti-methanogenic effect. In an in vitro system simulating rumen fermentation, we investigated the impact of eight compounds with distinct chemical characteristics (gallic and salicylic acids, tannic acid, catechin, epicatechin, quercetin, rutin, and salicin) when added to a basal feed (maize silage) at a concentration of 12% of the feed dry matter. After 48 h of incubation in buffered rumen fluid, methane production was significantly lowered by quercetin (43%), tannic acid (39%) and salicylic acid (34%) compared to the control (maize silage alone) and without changes in total volatile fatty acid production during fermentation. No other PSM reduced methane formation as compared to control but induced significant differences on total volatile fatty acid production. The observed differences were related to lipophilicity, the presence of double bond and carbonyl group, sugar moieties, and polymerization of the compounds. Our results indicate the importance of distinct molecular structures of PSMs and chemical characteristics for methane lowering properties and volatile fatty acid formation. Further systematic screening studies to establish the structure–function relationship between PSMs and methane reduction are warranted.

The Atlantic Zone Monitoring Program (AZMP) was established by Fisheries and Oceans Canada (DFO) in 1998 with the aim of monitoring physical and biological ocean conditions in Atlantic Canada in support of fisheries management. Since 2014, at least two of the carbonate parameters (pH; total alkalinity, TA; and dissolved inorganic carbon, DIC) have also been systematically measured as part of the AZMP, enabling the calculation of derived parameters (e.g., carbonate saturation states, Ω, and partial pressure of CO2, pCO2). The present study gives an overview of the spatiotemporal variability in these parameters between 2014 and 2022. Results show that the variability in the carbonate system reflects changes in both physical (e.g., temperature and salinity) and biological (e.g., plankton photosynthesis and respiration) parameters. For example, most of the region undergoes a seasonal warming and freshening. While the former will tend to increase Ω, the latter will decrease both TA and Ω. Spring and summer plankton blooms decrease DIC near the surface and then remineralize and increase DIC at depth in the fall. The lowest pCO2 values (down to ∼ 200 µatm) are located in the cold coastal Labrador Current, whereas the highest values (>1500 µatm) are found in the fresh waters of the Gulf of St. Lawrence and the St. Lawrence Estuary. The latter is also host to the lowest pH values of the zone (7.48 in the fall of 2022). Finally, most of the bottom waters of the Gulf of St. Lawrence (>90 %) are undersaturated with respect to aragonite (Ωarg). In addition to providing a baseline of carbonate parameters for the Atlantic Zone as a whole, this comprehensive overview is a necessary and useful contribution for the modelling community and for more in-depth studies. The full dataset of measured and derived parameters is available from the Federated Research Data Repository: https://doi.org/10.20383/102.0673 (Cyr et al., 2022a).

Abstract Organ donation is not meeting demand, and yet 30–60% of potential donors are potentially not identified. Current systems rely on manual identification and referral to an Organ Donation Organization (ODO). We hypothesized that developing an automated screening system based on machine learning could reduce the proportion of missed potentially eligible organ donors. Using routine clinical data and laboratory time-series, we retrospectively developed and tested a neural network model to automatically identify potential organ donors. We first trained a convolutive autoencoder that learned from the longitudinal changes of over 100 types of laboratory results. We then added a deep neural network classifier. This model was compared to a simpler logistic regression model. We observed an AUROC of 0.966 (CI 0.949–0.981) for the neural network and 0.940 (0.908–0.969) for the logistic regression model. At a prespecified cutoff, sensitivity and specificity were similar between both models at 84% and 93%. Accuracy of the neural network model was robust across donor subgroups and remained stable in a prospective simulation, while the logistic regression model performance declined when applied to rarer subgroups and in the prospective simulation. Our findings support using machine learning models to help with the identification of potential organ donors using routinely collected clinical and laboratory data.

Background. Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia–reperfusion injury to improve transplant outcomes. Methods. We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results. Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions. Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Abstract Introduction Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. Methods This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin