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ABSTRACT The Additively‐Manufactured, System‐Integrated Tip (AMSIT) project is leveraging the flexibility of 3D printing to integrate several technologies in a wind turbine blade tip, while reducing the levelized cost of electricity (LCOE) produced. The design integration is demonstrated for a 200‐kW–scale turbine with 13‐m blades, with the outer 15% of the blade replaced with a 3D‐printed design. Aerodynamic performance is enhanced without increasing swept area through inclusion of a winglet and surface texturing, both challenging for traditional manufacturing. Longevity and durability are improved through integrated lightning and leading edge erosion protection. Increased power, reduced repair frequency, and ease of repair through blade modularity all contribute to reduced LCOE. The analysis is also extended to modern MW‐scale designs to estimate the impact of the technology at scale, demonstrating the potential to reduce LCOE significantly for modern onshore turbines, with even higher potential savings offshore.

Abstract We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post‐RE (+65% and +36%, P

ABSTRACT Aims This study aimed to describe nurses' experiences caring for patients who use medicinal cannabis. For the purpose of this study, the term ‘medicinal cannabis’ is used to describe cannabis‐based products that are sourced legally or illegally. Design Qualitative study using thematic analysis. Methods Eleven registered nurses explored their experiences caring for patients using medicinal cannabis in the Australian healthcare sector. Semistructured interviews were via telephone, Zoom or face to face. Transcribed interview data were analysed using the six phases of thematic analysis. Results The nurses' experiences of caring for patients who use medicinal cannabis were described in three themes; ‘Searching for predictable processes of regulation, access and use of medicinal cannabis’, ‘One conundrum after another’ and ‘There is a lot to learn’. Overall, nurses described feeling underprepared to care for patients who use or want to use medicinal cannabis in the Australian healthcare sector. Conclusion The results indicate that nurses want to have meaningful discussions with patients about the use of medicinal cannabis, yet do not always have the confidence to do so. Nurses sought their own education on how to better support patients. All participants echoed the need for education. The nurse's role in caring for and supporting patients using medicinal cannabis could improve the patient experience. Implications for the Profession and/or Patient Care Nurses play an essential role in improving the patient's experience and advocating for those using or wanting to discuss medicinal cannabis as a part of holistic care. Defining the nurse's role in effectively caring for patients can begin by providing evidence‐based education to nurses. Including nurses in policy development and beginning to understand the legal and regulatory implications for nurses are important. Impact This is the first study presenting current issues for nurses who care for patients using medicinal cannabis in Australian healthcare systems. Reporting Method COREQ guidelines were adhered to for this study. No Patient or Public Contribution For this research project on the experiences of registered nurses caring for patients using medicinal cannabis, we did not engage members of the patient population or the general public.

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid–structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease. However, the clinical application of these techniques has been limited to hemodynamic assessment of coronary disease severity, with the potential to refine the assessment and management of coronary disease. Improved computational efficiency and large clinical trials are required to provide an incremental clinical benefit of these techniques beyond existing tools. This contemporary review is a clinically relevant overview of the disturbed coronary flow and its associated pathological consequences. The contemporary methods to assess disturbed flow are reviewed, including clinical applications of these techniques. Current limitations and future opportunities in the field are also discussed.

Abstract Postoperative care pathways for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion have demonstrated decreases in postoperative opioid consumption, improved pain control, and lead to decreased lengths of stay. Our objective was to implement postoperative steroids to reduce acute postoperative opioid consumption, pain scores, and length of stay. Dosing consisted of intravenous dexamethasone 0.1 mg/kg up to 4 mg per dose for a total of three doses at 8, 16, and 24 h postoperatively. As part of a quality initiative, we compared three cohorts of patients. The initial retrospective epidural cohort (EPI) (n = 59) had surgeon placed epidural catheters with infusion of ropivacaine 0.1% postoperatively for 18–24 h. Following an institutional change in postoperative care, epidural use was discontinued. A second cohort (n = 149), with prospectively collected data, received a surgeon placed erector spinae plane block and wound infiltration with a combination of liposomal and plain bupivacaine (LB). A third cohort (n = 168) was evaluated prospectively. This cohort received a surgeon placed erector spinae plane block and wound infiltration with liposomal and plain bupivacaine and additionally received postoperative dexamethasone for three doses (LB + D). Compared to the LB cohort, the LB + D cohort demonstrated statistically significant decreases in oral milligram morphine equivalents per kilogram at 0–24, 24–48, and 48–72 h. There was a statistically significant difference in median pain scores at 24–48 and 48–72 h in LB + D versus LB. The LB + D cohort's median length of stay in hours was significantly less compared to the LB cohort (52 h vs. 70 h, p

Abstract We selected 15 sheep‐grazed sand pastures along a gradient of increasing grazing intensity to study the fine‐scale patterns of main biomass fractions (green biomass, litter) and that of plant species and functional groups (life forms and social behaviour types). We classified them into five grazing intensity levels based on stocking density, proximity to drinking and resting places and the number of faeces. We aimed to answer the following questions: (i) How does increasing intensity of sheep grazing affect the amount of green biomass, the species richness and their relationship in sand pastures? (ii) How does increasing intensity of sheep grazing affect the biomass of perennial and short‐lived graminoids and forbs? (iii) How does the disturbance value—expressed in the biomass ratio of disturbance‐tolerant and ruderal species—change along the gradient of grazing intensity? A unimodal relationship between green biomass and species richness was detected; however, the ordination (canonical correspondence analysis, CCA) showed no clustering of pastures subjected to the same levels of grazing intensity. Along the grazing intensity gradient we found an increasing trend in species richness and significant differences in green biomass (decreasing trend), litter (decreasing trend), graminoids (decreasing trend) and short‐lived forbs (increasing trend). We found an increasing amount of disturbance‐tolerant and ruderal species with increasing grazing intensity. We suggest that we might need to use multiple scales for sampling and a fine‐scale assessment of grazing intensity. Our findings might be instructive for pastures in densely populated regions, which are prone to the encroachment of disturbance‐tolerant and ruderal species.

Abstract The Anthropocene has been framed around humanity's impact on atmospheric, biologic, and near‐surface processes, such as land use and vegetation change, greenhouse gas emissions, and the above‐ground hydrologic cycle. Groundwater extraction has lowered water tables in many key aquifers but comparatively little attention has been given to the impacts in the deeper subsurface. Here, we show that fluid fluxes from the extraction and injection of fluids associated with oil and gas production and inflow of water into mines likely exceed background flow rates in deep (>500 m) groundwater systems at a global scale. Projected carbon capture and sequestration (CCS), geothermal energy production, and lithium extraction to facilitate the energy transition will require fluid production rates exceeding current oil and co‐produced water extraction. Natural analogs and geochemical modeling indicate that subsurface fluid manipulation in the Anthropocene will likely appear in the rock record. The magnitude and importance of these changes are unclear, due to a lack of understanding of how deep subsurface hydrologic and geochemical cycles and associated microbial life interact with the rest of the Earth system.

Abstract Since the first applications of nanohoops in organic electronics appear promising, the time has come to go deeper into their rational design in order to reach high‐efficiency materials. To do so, systematic studies dealing with the incorporation of electron‐rich and/or electron‐poor functional units on nanohoops have to be performed. Herein, the synthesis, the electrochemical, photophysical, thermal, and structural properties of two [4]cyclo‐2,7‐carbazoles, [4]C‐Py‐Cbz, and [4]C‐Pm‐Cbz, possessing electron‐withdrawing units on their nitrogen atoms (pyridine or pyrimidine) are reported. The synthesis of these nanohoops is first optimized and a high yield above 50% is reached. Through a structure‐properties relationship study, it is shown that the substituent has a significant impact on some physicochemical properties (eg HOMO/LUMO levels) while others are kept unchanged (eg fluorescence). Incorporation in electronic devices shows that the most electrically efficient Organic Field‐Effect transistors are obtained with [4]C‐Py‐Cbz although this compound does not present the best‐organized semiconductor layer. These experimental data are finally confronted with the electronic couplings between the nanohoops determined at the DFT level and have highlighted the origin in the difference of charge transport properties. [4]C‐Py‐Cbz has the advantage of a more 2D‐like transport character than [4]C‐Pm‐Cbz, which alleviates the impact of defects and structural organization.

Abstract Problem Disordered eating, such as binge, graze, and emotional eating, has been strongly linked to weight gain. Improved understanding of disordered eating by adults who elect bariatric weight loss procedures in a real‐world setting is required. Purpose To determine the association between the number and type of disordered eating patterns (DEPs), as described by healthcare professionals during routine care without standardized assessment, with clinical outcomes in adults who elected a bariatric weight loss procedure. Method An observational cohort study recruited laparoscopic sleeve gastrectomy (LSG) and endoscopic sleeve gastroplasty (ESG) patients. DEPs documented in the medical record during routine care were observed and tested for association with events (symptoms, side‐effects, or adverse events), micronutrient deficiencies, weight loss, and attrition. Data were observed up to 12‐month post‐procedure. Results 215 LSG and 32 ESG patients were recruited. The mean number of DEPs was 6.4 (SD: 2.1) and 6.4 (SD: 2.1) in the LSG and ESG cohorts, respectively. Night eating was associated with a higher number of events (p

Abstract We recently reported that vastus lateralis (VL) cross‐sectional area (CSA) increases after 7 weeks of resistance training (RT, 2 days/week), with declines occurring following 7 weeks of subsequent treadmill high‐intensity interval training (HIIT) (3 days/week). Herein, we examined the effects of this training paradigm on skeletal muscle proteolytic markers. VL biopsies were obtained from 11 untrained college‐aged males at baseline (PRE), after 7 weeks of RT (MID), and after 7 weeks of HIIT (POST). Tissues were analysed for proteolysis markers, and in vitro experiments were performed to provide additional insights. Atrogene mRNAs (TRIM63, FBXO32, FOXO3A) were upregulated at POST versus both PRE and MID (P 0.05). in vitro experiments recapitulated the training phenotype when stimulated with a hypertrophic stimulus (insulin‐like growth factor 1; IGF1) followed by a subsequent AMP‐activated protein kinase activator (5‐aminoimidazole‐4‐carboxamide ribonucleotide; AICAR), as demonstrated by larger myotube diameter in IGF1‐treated cells versus IGF1 followed by AICAR treatments (I+A; P = 0.017). Muscle protein synthesis (MPS) levels were also greater in IGF1‐treated versus I+A myotubes (P

Abstract Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type‐5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate‐cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital‐based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory‐approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline‐recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory‐approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra‐patient efficacy of the two treatment approaches.

Abstract The cytokine interleukin (IL)‐11 has been shown to play a role in promoting fibrosis and cancer, including lung adenocarcinoma, garnering interest as an attractive target for therapeutic intervention. We used combinatorial methods to engineer an IL‐11 variant that binds with higher affinity to the IL‐11 receptor and stimulates enhanced receptor‐mediated cell signaling. Introduction of two additional point mutations ablates IL‐11 ligand/receptor association with the gp130 coreceptor signaling complex, resulting in a high‐affinity receptor antagonist. Unlike wild‐type IL‐11, this engineered variant potently blocks IL‐11‐mediated cell signaling and slows tumor growth in a mouse model of lung cancer. Our approach highlights a strategy where native ligands can be engineered and exploited to create potent receptor antagonists.

Abstract Chiral molecules are known to behave as spin filters due to the chiral induced spin selectivity (CISS) effect. Chirality can be implemented in molecular semiconductors in order to study the role of the CISS effect in charge transport and to find new materials for spintronic applications. In this study, the design and synthesis of a new class of enantiopure chiral organic semiconductors based on the well‐known dinaphtho[2,3‐b:2,3‐f]thieno[3,2‐b]thiophene (DNTT) core functionalized with chiral alkyl side chains is presented. When introduced in an organic field‐effect transistor (OFET) with magnetic contacts, the two enantiomers, (R)‐DNTT and (S)‐DNTT, show an opposite behavior with respect to the relative direction of the magnetization of the contacts, oriented by an external magnetic field. Each enantiomer displays an unexpectedly high magnetoresistance over one preferred orientation of the spin current injected from the magnetic contacts. The result is the first reported OFET in which the current can be switched on and off upon inversion of the direction of the applied external magnetic field. This work contributes to the general understanding of the CISS effect and opens new avenues for the introduction of organic materials in spintronic devices.

Abstract Over the past 4 years, the authors have participated as members of the Mobilizing Computable Biomedical Knowledge Technical Infrastructure working group and focused on conceptualizing the infrastructure required to use computable biomedical knowledge. Here, we summarize our thoughts and lay the foundation for future work in the development of CBK infrastructure, including: explaining the difference between computable knowledge and data, and contextualizing the conversation with the Learning Health Systems and the FAIR principles. Specifically, we provide three guiding principles to advance the development of CBK infrastructure: (a) Promote interoperable systems for data and knowledge to be findable, accessible, interoperable, and reusable. (b) Enable stable, trustworthy knowledge representations that are human and machine readable. (c) Computable knowledge resources should, when possible, be open. Standards supporting computable knowledge infrastructures must be open.

Abstract How subsurface microbial life changed at the bottom of the kilometers‐deep (hypo) Critical Zone in response to evolving surface conditions over geologic time is an open question. This study investigates the burial and exhumation, biodegradation, and fluid circulation history of hydrocarbon reservoirs across the Colorado Plateau as a window into the hypo‐Critical Zone. Hydrocarbon reservoirs, in the Paradox and Uinta basins, were deeply buried starting ca. 100 to 60 Ma, reaching temperatures >80–140°C, likely sterilizing microbial communities present since the deposition of sediments. High salinities associated with evaporites may have further limited microbial activity. Upward migration of hydrocarbons from shale source rocks into shallower reservoirs during maximum burial set the stage for microbial re‐introduction by creating organic‐rich “hot spots.” Denudation related to the incision of the Colorado River over the past few million years brought reservoirs closer to the surface under cooler temperatures, enhanced deep meteoric water circulation and flushing of saline fluids, and likely re‐inoculated more permeable sediments up to several km depth. Modern‐ to paleo‐hydrocarbon reservoirs show molecular and isotopic evidence of anaerobic oxidation of hydrocarbons coupled to bacterial sulfate reduction in areas with relatively high SO4‐fluxes. Anaerobic oil biodegradation rates are high enough to explain the removal of at least some portion of postulated “supergiant oil fields” across the Colorado Plateau by microbial activity over the past several million years. Results from this study help constrain the lower limits of the hypo‐Critical Zone and how it evolved over geologic time, in response to changing geologic, hydrologic, and biologic forcings.

Abstract Limited research exists examining how resistance training to failure affects applied outcomes and single motor unit characteristics in previously trained individuals. Herein, resistance‐trained adults (24 ± 3 years old, self‐reported resistance training experience was 6 ± 4 years, 11 men and 8 women) were randomly assigned to either a low‐repetitions‐in‐reserve (RIR; i.e., training near failure, n = 10) or high‐RIR (i.e., not training near failure, n = 9) group. All participants implemented progressive overload during 5 weeks where low‐RIR performed squat, bench press, and deadlift twice weekly and were instructed to end each training set with 0–1 RIR. high‐RIR performed identical training except for being instructed to maintain 4–6 RIR after each set. During week 6, participants performed a reduced volume‐load. The following were assessed prior to and following the intervention: (i) vastus lateralis (VL) muscle cross‐sectional area (mCSA) at multiple sites; (ii) squat, bench press, and deadlift one‐repetition maximums (1RMs); and (iii) maximal isometric knee extensor torque and VL motor unit firing rates during an 80% maximal voluntary contraction. Although RIR was lower in the low‐ versus high‐RIR group during the intervention (p

Abstract Trophic cascades are important features of aquatic ecosystems, but much variation in their strength remains unexplained. Disturbance could restrict cascade occurrence by limiting predator distribution, and increase cascade strength by lowering defended herbivore abundance. These possibilities were investigated in 20 New Zealand rivers varying both in flooding disturbance (measured by bed movement) and presence of non‐native predatory trout. Trout were often, but not always, associated with indirectly increasing algal abundance compared to similar rivers with native galaxiid fishes. Floods explained variation in cascades by (1) resetting algal abundance such that algal minima were related to bed movement; (2) preventing occurrence by restricting trout abundance in the most disturbed rivers; and (3) increasing potential cascade strength by removing defended herbivores. These observations indicate strong nonlinear influences of disturbance on both trophic cascade occurrence and maximum strength which will be important to consider as climate change alters disturbance regimes.

Abstract Background Friedreich’s ataxia is an inherited, progressive, neurodegenerative disease that typically begins in childhood. Disease severity is commonly assessed with rating scales, such as the modified Friedreich’s Ataxia Rating Scale, which are usually administered in the clinic by a neurology specialist. Objective This study evaluated the utility of home‐based, self‐administered digital endpoints in children with Friedreich’s ataxia and unaffected controls and their relationship to standard clinical rating scales. Methods In a cross‐sectional study with 25 participants (13 with Friedreich’s ataxia and 12 unaffected controls, aged 6–15 years), home‐based digital endpoints that reflect activities of daily living were recorded over 1 week. Domains analyzed were hand motor function with a digitized drawing, automated analysis of speech with a recorded oral diadochokinesis test, and gait and balance with wearable sensors. Results Hand‐drawing and speech tests were easy to conduct and generated high‐quality data. The sensor‐based gait and balance tests suffered from technical limitations in this study setup. Several parameters discriminated between groups or correlated strongly with modified Friedreich’s Ataxia Rating Scale total score and activities of daily living total score in the Friedreich’s ataxia group. Hand‐drawing parameters also strongly correlated with standard 9‐hole peg test scores. Interpretation Deploying digital endpoints in home settings is feasible in this population, results in meaningful and robust data collection, and may allow for frequent sampling over longer periods of time to track disease progression. Care must be taken when training participants, and investigators should consider the complexity of the tasks and equipment used.

Abstract Background Meaningful consumer involvement in health research is important. There are limited data on how to maintain long‐term consumer involvement. Objective To identify barriers and facilitators to meaningful long‐term consumer involvement in research. Design Six semi‐structured interviews were conducted with members of the Primary Care Collaborative Cancer Clinical Trials Group (PC4) Community Advisory Group (CAG) and included the review of 40 supporting documents. Interviews and documents were analysed using inductive thematic analysis; the themes were mapped onto the domains of Cancer Australia's National Framework for Consumer Involvement in Cancer Control. Results Equality, respect and feeling valued were facilitators to long‐term involvement. These elements were part of an overarching theme of organizational commitment. Creating balance, managing competing deadlines and integrating a consumer role with a personal life were key barriers to involvement. These themes mapped strongly to the National Framework for Consumer Involvement in Cancer Control domains of committed organizations, capable consumers, inclusive groups and shared focus. Conclusion Research networks should reflect on several factors to maintain long‐term consumer involvement. Networks should aim to build a meaningful relationship, using clear communication and education, that reinforces the value and scope of a consumers contributions. We found that consumer education needs do not diminish over time and adequate skill development, support and feedback need to be on‐going. Creating regular opportunities for feedback and reflection are important to continue to meet best practice guidelines.

Abstract High‐resolution bathymetry and three‐dimensional seismic data along the Cocos Ridge reveal a 245 km2 field of ∼1–4 km in diameter seafloor depressions. The seafloor depressions are part of a two‐tiered honeycomb pattern. The lower‐tier depressions have steep faults that truncate strata with chaotic internal reflections consistent with sediment collapse into the depression. These extend into a lens shaped interval just above igneous basement. Overlying these depressions is a second broader set with rough seafloor morphology with gently dipping boundaries defined by pinch‐out stratigraphic patterns. Drilling results indicate that the lens‐shaped zones that host the deeper depressions represent anomalous regions of high porosity, low velocity, and low density within calcareous rich sediment. Analysis of nannofossils from IODP Site U1414 suggests the collapse structures formed during the late Miocene, whereas the younger shallower depressions likely formed between the early Pliocene and the Pliocene‐Pleistocene boundary. Geochemical and petrological analysis at Site U1414 suggests that hydrothermal circulation during the late Miocene led to carbonate dissolution and collapse. Following collapse, focused fluid‐flow and bottom current scouring resulted in formation of the overlying set of depressions and a honeycomb seafloor morphology. Similar sets of depressions along the Carnegie Ridge to the south support the hypothesis that two‐tiered depressions formed in response to processes that occurred broadly across the Panama Basin between the late Miocene and the Pliocene‐Pleistocene transition. Geochemical results at Site U1414, combined with geophysical data, suggest this two‐tiered system of depressions currently guides ongoing fluid outflow.

Abstract The charge transport of crystalline organic semiconductors is limited by dynamic disorder that tends to localize charges. It is the main hurdle to overcome in order to significantly increase charge carrier mobility. An innovative design that combines a chemical structure based on sulfur‐rich thienoacene with a solid‐state herringbone (HB) packing is proposed and the synthesis, physicochemical characterization, and charge transport properties of two new thienoacenes bearing a central tetrathienyl core fused with two external naphthyl rings: naphtho[2,3‐b]thieno‐[2′′′,3′′′:4′′,5′′]thieno[2″,3″:4′,5′]thieno[3′,2′‐b]naphtho[2,3‐b]thiophene (DN4T) and naphtho[1,2‐b]thieno‐[2′′′,3′′′:4′′,5′′]thieno[2′′,3′′:4′,5′]thieno[3′,2′‐b]naphtho[1,2‐b]thiophene are presented. Both compounds crystallize with a HB pattern structure and present transfer integrals ranging from 33 to 99 meV (for the former) within the HB plane of charge transport. Molecular dynamics simulations point toward an efficient resilience of the transfer integrals to the intermolecular sliding motion commonly responsible for strong variations of the electronic coupling in the crystal. Best device performances are reached with DN4T with hole mobility up to μ = 2.1 cm2 V−1s−1 in polycrystalline organic field effect transistors, showing the effectiveness of the electronic coupling enabled by the new aromatic core. These promising results pave the way to the design of high‐performing materials based on this new thienoacene, notably through the introduction of alkyl side‐chains.

Abstract The generalizable functional attributes of organisms (traits) relate strongly to their environment across multiple levels of biological organization, making trait‐based approaches a powerful mechanistic framework to understand species distributions and community composition in relation to environmental change. To investigate how a wide range of stressor types shape stream macroinvertebrate communities, we conducted an integrative analysis using community and taxon trait information across drying, flooding, eutrophication, fine sediment, and acid mine drainage (AMD) gradients. Each gradient spanned relatively unimpacted to severely impacted sites. To characterize community change in response to stressors, we incorporated abundance‐based trait information from all stressor gradients in a single trait‐based ordination (nonmetric multidimensional scaling), defining the trait space within which each stressor gradient acted. We hypothesized that different stressors would apply different environmental filters, moving communities along distinct axes in trait space and resulting in communities with definable trait combinations. Particularly strong relationships were associated with anthropogenically derived stressors (fine sediment, eutrophication, and AMD) compared to natural stressors (drying and flooding). Anthropogenic stressors instigated significant movement of communities along multiple axes in trait space, likely driven by limited adaptation to these novel stressors. We demonstrate that trait‐based analysis of communities across multiple stressor gradients can support a more comprehensive understanding of how community composition changes than taxonomic methods or investigation of a single stressor type, and could underpin community‐focused management actions.

Abstract Wild Pacific salmon, including Chinook salmon Oncorhynchus tshawytscha, have been supplemented with hatchery propagation for over 50 years in support of increased ocean harvest, mitigation for hydroelectric development, and conservation of threatened populations. In Canada, the Wild Salmon Policy for Pacific salmon was established with the goal of maintaining and restoring healthy and diverse Pacific salmon populations, making conservation of wild salmon and their habitats the highest priority for resource management decision‐making. For policy implementation, a new approach to the assessment and management of Chinook salmon and the associated hatchery production and fisheries management are needed. Implementation of genetic stock identification (GSI) and parentage‐based tagging (PBT) for marine fisheries assessment may overcome problems associated with coded‐wire tag‐based (CWT) assessment and management of Chinook salmon fisheries, providing at a minimum information equivalent to that derived from the CWT program. GSI and PBT were used to identify Chinook salmon sampled in 2018 and 2019 marine fisheries (18,819 individuals genotyped) in British Columbia to specific conservation units (CU), populations, and broodyears. Individuals were genotyped at 391 single nucleotide polymorphisms via direct sequencing of amplicons. Very high accuracy of assignment to population and age (>99.5%) via PBT was observed for 1994 Chinook salmon of ages 2–4 years, with a 105,722–individual, 380–population baseline available for assignment. Application of a GSI‐PBT system of identification to individuals in 2019 fisheries provided high‐resolution estimates of stock composition, catch, and exploitation rate by CU or population, with fishery exploitation rates directly comparable to those provided by CWTs for 13 populations. GSI and PBT provide an alternate, cheaper, and more effective method in the assessment and management of Canadian‐origin Chinook salmon relative to CWTs, and an opportunity for a genetics‐based system to replace the current CWT system for salmon assessment.

Abstract Objective To define the value of a digital rectal exam (DRE) in the prostate‐magnetic resonance imaging (MRI) era. Prostate MRI is increasingly used in men with elevated prostate‐specific antigen (PSA) prior to biopsy. Methods A retrospective study was performed in men with elevated PSA undergoing MRI followed by MRI fusion with systematic biopsy and men with elevated PSA/active surveillance with negative MRI followed by biopsy. Baseline clinicopathologic characteristics and DRE findings were collected. We examined performance of a positive DRE on sensitivity and specificity of diagnosing clinically significant prostate cancer (CSPC). Results A total of 339 patients had elevated PSA and positive MRI followed by MRI fusion guided with systematic biopsy. Pre‐biopsy DRE was documented in 286/339 patients, who were included in further analysis. About 81.6% positive, 78.7% questionable, and 55.8% negative DRE patients had CSPC. Positive DRE had 21.8% sensitivity and 91.3% specificity for CSPC. Positive or questionable DRE had 42.1% sensitivity and 81.5% specificity. Among 148 men with non‐CSPC (GG1)‐targeted biopsy, 28 had systematic biopsy with CSPC. About 5/28 had positive DRE and 8/28 had positive or questionable DRE. Twenty‐seven patients were included who had elevated PSA/on active surveillance with negative MRI and biopsy done within 2 years. About 77.8% had negative, 7.4% had questionable, and 14.8% men had positive DRE. About 7.4% had CSPC and all had a negative DRE. Conclusions Our study provides limited evidence for the value of a DRE. However, it does show occasional benefit in detecting GG2 or higher disease and given the lack of cost and side effects, should still be considered.

Abstract Customary harvests of wildlife underpin the livelihoods, cultural identities, well‐being and ecological knowledge of many Indigenous peoples and local communities (IPLC), whereas government restrictions on harvests can erode these relationships. Supporting IPLC in place‐based resource management, including sustainable customary harvests, can aid wildlife, their habitat and the cultures that value them. Using an experiment jointly initiated by the Māori tribe Ngāi Tahu and researchers (Māori and non‐Māori) in Aotearoa/New Zealand, we identified low‐impact strategies for harvesting black swan (kakī anau, Cygnus atratus) eggs at an important coastal lagoon, Te Waihora/Lake Ellesmere. The experiment tested whether nest‐level hatching success (number of eggs hatched) depended on nest‐level harvest pressure; whether this effect was additive; and the extent to which harvest influenced post‐harvest egg laying and hatching probability, relative to several control variables. Nest‐level harvest pressure determined nest‐level hatching success and had a non‐additive effect on population‐level hatching success. Specifically, harvesting one‐third or two‐thirds of a clutch caused a loss of approximately one hatchling per egg removed, because swans tended to replace few of those harvested eggs and hatching probability of unharvested eggs was generally high (but lower in nests with two‐thirds of eggs removed). Conversely, harvesting an entire clutch caused a loss of approximately one hatchling for every two eggs removed, because swans often subsequently re‐laid new, albeit smaller, clutches. During fixed‐output harvests, removing entire clutches early during nesting could induce re‐laying and prevent abandonment of unharvested eggs. Moreover, harvesting from areas of nesting colonies with low nest density, where hatching probability of unharvested eggs was lowest, could limit disturbance. Finally, restoring foraging habitat in degraded wetlands surrounding nutrient‐overloaded waterbodies could offset eutrophication effects by providing plant resources that swans require to lay eggs indeterminately. In addition to improving IPLC well‐being, implementing strategies such as these could enhance place‐based resource management by supporting IPLC engagement with nature, which increases the number and detection resolution of ecological feedbacks (e.g. population numbers, habitat conditions) and resilience to environmental change. Moreover, customary harvest could be a practical, culturally appropriate and less wasteful alternative to non‐consumptive culling for mitigating human–wildlife conflict (e.g. waterfowl grazing on pasture). A free Plain Language Summary can be found within the Supporting Information of this article.

Abstract Objective ‘First seizure’ clinics (FSCs) aim to achieve early expert assessment for individuals with possible new‐onset epilepsy. These clinics also have substantial potential for research into epilepsy evolution, outcomes, and costs. However, a paucity of FSCs details has implications for interpretation and utilization of this research. Methods We reviewed investigation findings over 11 years (2000‐2010) from two established independent FSCs at Austin Health (AH) and Royal Melbourne Hospital (RMH), Australia. These adult clinics are in major public hospitals and operate with similar levels of expertise. Organizational differences include screening and dedicated administration at AH. Included were N = 1555 patients diagnosed with new‐onset unprovoked seizures/epilepsy (AH n = 901, RMH n = 654). Protocol‐driven interviews and investigations had been recorded prospectively and were extracted from medical records for study. Results Median patient age was 37 (IQR 26‐52, range 18‐94) years (AH 34 vs RMH 42 years; P

Abstract Conservation translocations—particularly those that weave diverse ways of knowing and seeing the world—promise to enhance species recovery and build ecosystem resilience. Yet, few studies to date have been led or co‐led by Indigenous peoples; or consider how centring Indigenous knowledge systems can lead to betterconservation translocation outcomes. In this Perspective, as Indigenous and non‐Indigenous researchers and practitioners working in partnership in Aotearoa New Zealand, we present a novel framework for co‐designing conservation translocations that centre Indigenous peoples and knowledge systems through Two‐Eyed Seeing. We apply this framework to Aotearoa New Zealand's threatened and underprioritized freshwater biodiversity. In particular, we highlight the co‐development of conservation translocations with Te Kōhaka o Tūhaitara and Te Nohoaka o Tukiauau that are weaving emerging genomic approaches into mātauraka Māori (Māori knowledge systems), including customary practices, processes and language. We envision the Two‐Eyed Seeing framework presented here will provide a critical point of reference for the co‐development of conservation translocations led or co‐led by Indigenous peoples elsewhere in the world to build more resilient biocultural heritage. A free Plain Language Summary can be found within the Supporting Information of this article.

Abstract For Pacific salmon, the key fisheries management goal in British Columbia (BC) is to maintain and restore healthy and diverse Pacific salmon populations, making conservation of salmon biodiversity the highest priority for resource management decision‐making. Salmon status assessments are often conducted on coded‐wire‐tagged subsets of indicator populations based on assumptions of little differentiation within or among proximal populations. In the current study of southern BC coho salmon (Oncorhynchus kisutch) populations, parentage‐based tagging (PBT) analysis provided novel information on migration and life‐history patterns to test the assumptions of biological homogeneity over limited (generally

Abstract Multifocal (MF)/multicentric (MC) breast cancer is generally considered to be where two or more breast tumours are present within the same breast, and is seen in ~10% of breast cancer cases. This study investigates the prevalence of multifocality/multicentricity in a cohort of BRCA1/2 mutation carriers with breast cancer from Northern Ireland via cross‐sectional analysis. Data from 211 women with BRCA1/2 mutations (BRCA1‐91, BRCA2‐120) and breast cancer were collected including age, tumour focality, size, type, grade and receptor profile. The prevalence of multifocality/multicentricity within this group was 25% but, within subgroups, prevalence amongst BRCA2 carriers was more than double that of BRCA1 carriers (p = 0.001). Women affected by MF/MC tumours had proportionately higher oestrogen receptor positivity (p = 0.001) and lower triple negativity (p = 0.004). These observations are likely to be driven by the higher BRCA2 mutation prevalence observed within this cohort. The odds of a BRCA2 carrier developing MF/MC cancer were almost four‐fold higher than a BRCA1 carrier (odds ratio: 3.71, CI: 1.77–7.78, p = 0.001). These findings were subsequently validated in a second, large independent cohort of patients with BRCA‐associated breast cancers from a UK‐wide multicentre study. This confirmed a significantly higher prevalence of MF/MC tumours amongst BRCA2 mutation carriers compared with BRCA1 mutation carriers. This has important implications for clinicians involved in the treatment of BRCA2‐associated breast cancer, both in the diagnostic process, in ensuring that tumour focality is adequately assessed to facilitate treatment decision‐making, and for breast surgeons, particularly if breast conserving surgery is being considered as a treatment option for these patients.

ABSTRACT Introduction Computational brain network modeling using The Virtual Brain (TVB) simulation platform acts synergistically with machine learning (ML) and multi‐modal neuroimaging to reveal mechanisms and improve diagnostics in Alzheimer's disease (AD). Methods We enhance large‐scale whole‐brain simulation in TVB with a cause‐and‐effect model linking local amyloid beta (Aβ) positron emission tomography (PET) with altered excitability. We use PET and magnetic resonance imaging (MRI) data from 33 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI3) combined with frequency compositions of TVB‐simulated local field potentials (LFP) for ML classification. Results The combination of empirical neuroimaging features and simulated LFPs significantly outperformed the classification accuracy of empirical data alone by about 10% (weighted F1‐score empirical 64.34% vs. combined 74.28%). Informative features showed high biological plausibility regarding the AD‐typical spatial distribution. Discussion The cause‐and‐effect implementation of local hyperexcitation caused by Aβ can improve the ML–driven classification of AD and demonstrates TVB's ability to decode information in empirical data using connectivity‐based brain simulation.

Abstract Global groundwater volumes in the upper 2 km of the Earth's continental crust—critical for water security—are well estimated. Beyond these depths, a vast body of largely saline and non‐potable groundwater exists down to at least 10 km—a volume that has not yet been quantified reliably at the global scale. Here, we estimate the amount of groundwater present in the upper 10 km of the Earth's continental crust by examining the distribution of sedimentary and crystalline rocks with depth and applying porosity‐depth relationships. We demonstrate that groundwater in the 2–10 km zone (what we call “deep groundwater”) has a volume comparable to that of groundwater in the upper 2 km of the Earth's crust. These new estimates make groundwater the largest continental reservoir of water, ahead of ice sheets, provide a basis to quantify geochemical cycles, and constrain the potential for large‐scale isolation of waste fluids.