Performance outcome (PerfO) assessments are standardized, task-based clinical outcome assessments (COAs) used to evaluate patients' physical, cognitive, sensory, and functional abilities in clinical trials. Building on the first ISPOR PerfO Task Force report, which addressed selection, development, and modification of PerfO instruments, this second task force report focuses on clinical trial implementation considerations that are especially relevant to PerfO assessments, when compared to other clinical outcome assessment types. Examples of PerfO Assessments related to specific aspects of function (sensory, motor, cognitive, daily, ambulatory, and neurodevelopmental) are presented. Practical considerations related to clinical trial design, standardized documentation, administrator training, data collection and use of digital health technologies to enable reliable data collection are provided. Factors that jeopardize validity (including disease progression, learning effects, encouragement effects, and sensory or cognitive limitations) are identified alongside targeted mitigation strategies. As no analytic technique can compensate for inconsistent PerfO assessment implementation, careful planning and consistent monitoring of data collection is foundational to ensuring data are valid and interpretable.

The Aspen Health Strategy Group's 2026 meeting, cosponsored by Ardmore Institute of Health, focused on Food and Health, including the issue of food is medicine. This commentary argues that the field's promise is greatest when framed more broadly as Food as Health, Prevention, and Medicine. Food is not only a therapeutic intervention after diagnosis, but a daily determinant of whole-person health, community well-being, and chronic disease prevention. Advancing this vision requires clinical, policy, cultural, and community-based strategies that make healthy food accessible and meaningful.

This study presents an integrated techno-economic and life cycle assessment (LCA) of a biorefinery for the valorization of cotton-polyester textile waste (50/50 wt%) into LA, TPA, and EG under three pretreatment strategies: alkaline (Na2CO3), organosolv (NMMO), and acidic (H3PO4). The system processes 72,000 t/y of post-consumer textiles and is modelled using Aspen Plus and Aspen PEA for process simulation and economic evaluation, and SimaPro with ReCiPe 2016 for environmental assessment in accordance with ISO 14040/14044 standards. Results indicate that pretreatment selection significantly affects process performance. The alkaline route achieves the lowest total capital investment (133.60 M$), highest internal rate of return (29.1 %), and shortest payback period (3.34 years). The organosolv route produces the highest LA output (18,145 t/y), while the acidic route yields the highest TPA (25,715 t/y) and EG (8,214 t/y), but also the highest capital (202.34 M$) and operating costs (35.28 M$/y). The midpoint LCA results showed that the alkaline pathway generally had the lowest environmental impacts across most categories, although category-specific trade-offs were observed. The endpoint single scores were 50.07, 77.38, and 104.35 mPt/FU for LA; 40.69, 62.87, and 84.76 mPt/FU for TPA; and 29.43, 45.47, and 61.31 mPt/FU for EG for the alkaline, organosolv, and acidic pathways, respectively. Compared with conventional production, the evaluated pathways generally showed lower environmental burdens, although this advantage varied among products and pretreatment routes. Overall, the alkaline pathway demonstrated the most favorable environmental performance among the evaluated strategies.

Cancer genomics and precision oncology are increasingly central to cancer care, but many health systems struggle to implement them equitably, effectively, and sustainably. This Commission defines the current global precision oncology landscape and analyses the scientific, structural, and health-system challenges shaping its delivery and impact. Findings indicate that access to cancer genomics and precision oncology remains profoundly unequal across and within countries, leaving millions of patients without guideline-indicated interventions each year. These disparities extend to research, with genomic studies and clinical trials concentrated in high-income settings and among populations of predominantly European ancestry. At the same time, fragmented and poorly integrated data ecosystems restrict evidence generation, knowledge sharing, and clinical impact. Beyond questions of access and implementation, the clinical benefit of precision oncology is highly heterogeneous. The greatest and most consistent gains are confined to a few well validated biomarker-treatment pairings, typically supported by companion diagnostics; broader approaches such as comprehensive genomic profiling and tumour-agnostic strategies, might expand options for selected patients, but only a few patients receiving matched therapy derive meaningful benefit. The Commission also identifies a paradox of success: rapid expansion of precision oncology has increased cognitive, organisational, data, workforce, and financial burdens, while evidence of broad population-level benefit has lagged behind. In response, the Commission offers a comprehensive and context-responsive approach for integrating cancer genomics and precision oncology into health systems effectively, equitably, and sustainably. The Commission developed a value-based resource-stratified implementation framework, a system-readiness assessment tool, a precision oncology workforce competency-based framework, a precision oncology monitoring and evaluation framework, and principles for responsible data sharing and health-system learning. Cancer genomics and precision oncology can improve outcomes and strengthen health systems if scaled equitably, sustainably, and according to evidence, public value, national context, and patient needs. This Commission offers a basis for global consensus on a more equitable, evidence-informed, and sustainable path forward.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic airway disease characterized by recurrent infection, mucus retention, neutrophilic inflammation, and pulmonary exacerbations. Brensocatib is an oral, selective, reversible dipeptidyl peptidase 1 (DPP1) inhibitor that reduces neutrophil serine protease activation and has received regulatory approval for non-cystic fibrosis bronchiectasis in patients aged 12 years and older.

Evorpacept blocks the CD47-signal regulatory protein α interaction, enhancing antibody-dependent cellular phagocytosis. In the phase 2 portion of ASPEN-06 (a multicenter, open-label, randomized phase 2/3 study), 127 patients with pretreated, human epidermal growth factor receptor 2 (HER2)-overexpressing, advanced gastric/gastroesophageal junction cancer were randomized to evorpacept plus trastuzumab, ramucirumab and paclitaxel (evo + TRP; n = 63; fresh HER2[+] biopsy, n = 22) or TRP alone (n = 64; fresh HER2[+] biopsy, n = 26). The primary end point was investigator-assessed objective response rate (ORR). The primary analysis of ORR was designed to evaluate an ORR exceeding the historical 30% benchmark (ramucirumab/paclitaxel) (80% power for intent to treat (ITT) and 50% power for the ITT subpopulation (HER2 overexpression based on a post-trastuzumab 'fresh' biopsy)) and an improvement of ≥8.0% and ≥9.7% versus TRP in the ITT and ITT subpopulations, respectively. Key secondary end points included ORR by blinded independent central review, duration of response and progression-free survival by investigator or blinded independent central review, overall survival and safety. Post hoc biomarker analyses, including the assessment of the association of treatment efficacy with retained HER2 status (defined by HER2 positivity on fresh tumor biopsy or amplification in circulating tumor DNA analysis) and CD47 expression in tumor samples, were conducted. The investigator-assessed ORRs were 40.3% (evo + TRP) versus 26.6% (TRP) in the ITT population and 54.8% versus 23.1% in the fresh biopsy HER2[+] subgroup. ORR differences (13.7% and 31.7%) exceeded the prespecified thresholds in both the ITT population and fresh biopsy HER2[+] subgroup, meeting one of the two primary objectives; however, compared to the historical benchmark (30%), ORRs in the ITT population (40.3%; P = 0.0949, one-sided) and fresh biopsy HER2[+] subgroup (54.8%; P = 0.030, one-sided) did not meet the prespecified statistical criterion (one-sided α = 0.025). While hematologic toxicities were more common with evo + TRP, overall safety was similar. In summary, evo + TRP showed encouraging efficacy with manageable safety in advanced gastric/gastroesophageal junction cancer. ClinicalTrials.gov identifier: NCT05002127 .

Patients with cancer have an increased risk of venous thromboembolism (VTE). This risk is further elevated in those with a central venous catheter (CVC). Previous studies have shown that prophylactic doses of direct oral anticoagulants (DOACs) reduce the risk of VTE in ambulatory cancer patients starting chemotherapy, which has led to recommendations from international clinical guidelines to use DOACs as primary thromboprophylaxis in this population. Primary thromboprophylaxis after CVC insertion is not recommended due to a lack of definitive evidence. As such, the TRIM-Line trial randomized 1,828 patients with active cancer and a newly inserted CVC to rivaroxaban 10 mg daily versus placebo. The primary efficacy outcome was the first objectively confirmed symptomatic or incidental major VTE (proximal upper or lower extremity deep vein thrombosis and/or pulmonary embolism) within 90 days of randomization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Haemostasis criteria, within 90 days. The key secondary outcomes included clinically relevant non-major bleeding, arterial thrombosis, and overall mortality. The study provides high-quality evidence to address a key knowledge gap regarding the benefits and risks of thromboprophylaxis in patients with active cancer and an indwelling CVC (NCT05029063).

Nitrate functions both as a nutrient and a signaling molecule, but how nitrate is perceived and translated into developmental outputs within woody tissues is unknown. Here, we show that developing xylem in hybrid aspen (Populus tremula × P. tremuloides) mounts a rapid, cell-type-specific transcriptional response to nitrate that promotes xylem cell expansion. To isolate local nitrate signaling in wood-forming tissues, we delivered nitrate directly into the xylem sap and profiled transcriptomic responses from 2 to 48 h after treatment. Bulk RNA sequencing revealed a transient response peaking within 2-4 h. Single-cell RNA sequencing at the peak response resolved nitrate signaling across developing xylem cell types and showed that nitrate induced cell-type-specific programs linked to nitrogen transport, cell wall remodeling, and developmental progression, while repressing lignin-biosynthetic genes. These data indicate that nitrate acts transiently in wood-forming tissues to fine-tune early xylem development. Among nitrate-responsive transcription factors, CYTOKININ RESPONSE FACTOR 4 (CRF4) emerged as a candidate regulator of this response. CRF4 overexpression in hybrid aspen stimulated xylem cell expansion, whereas simultaneous knock-out of CRF4 and its paralog, CRF3, significantly attenuated the nitrate-induced expansion. Together, our findings identify a local nitrate signaling module in developing wood and establish CRF4 as a component linking nitrate sensing to xylem cell expansion.

Boreal forests cover a substantial portion of Canada's land base and play a central role in the national carbon budget through carbon storage and fluxes across multiple above- and belowground pools. The Carbon Budget Model of the Canadian Forest Sector (CBM-CFS3) simulates and projects forest carbon dynamics under varying conditions and management scenarios, and ongoing model evaluation and calibration are essential to maintain accuracy in carbon monitoring, accounting, and reporting. This study assesses CBM-CFS3 performance using independent ground plot data from 64 aspen-dominated stands that have been monitored since 2000 as part of the Climate Impacts on the Productivity and Health of Aspen (CIPHA) project. We compared modeled and observed C stocks in aboveground biomass, snags, forest floor, and mineral soil pools, and examined the influence of stand characteristics, climate variables, and soil chemical properties on model residuals. Model performance varied across carbon pools: CBM-CFS3 most accurately simulated aboveground biomass C stocks, performed moderately well for snags, but failed to capture spatial variability in forest floor and mineral soil C stocks. Our findings suggest that incorporating stand density into the yield curve model and stand age into volume-to-biomass conversion equations would enhance the accuracy of aboveground biomass C stock estimates in aspen-dominated stands. Representation of snag carbon dynamics could be improved by accounting for lagged mortality following drought events and by increasing snag fall rates. Further refinement of forest floor carbon dynamics will require integrating the influence of moisture on organic matter decomposition, while improving mineral soil carbon dynamics will require incorporating the effect of clay content on decomposition and reducing the temperature sensitivity of decay. Because these pools are interdependent, refinements in one pool will have cascading effects on downstream pools and overall carbon dynamics. The CBM-CFS3 remains a key tool for national carbon estimation, and the availability of high spatial and temporal resolution data, such as CIPHA, for model evaluation will further strengthen the model's predictive capability.

Biomass and waste gasification offer a renewable pathway to methanol via syngas, yet the stringent impurity limits required by commercial methanol catalysts make syngas cleaning a critical step in the process. In this review, we first define the optimal syngas composition for economical methanol production based on literature data. It then establishes a systematic link between gasification conditions, raw gas (RG) composition, and downstream cleaning requirements. Unlike previous reviews that mainly focus on individual gas cleaning technologies, this work integrates impurity specifications required for methanol synthesis with gasification conditions, downstream cleaning strategies, and recent advances in gasification and cleaning process modeling. The influences of feedstock composition, gasifier type, and gasification medium on RG composition and impurity levels, including tars, particulates, sulfur species, halides, nitrogen compounds, and trace metals, are examined as factors determining the design and severity of downstream cleaning trains and necessary gas conversions. Key cleaning technologies, including high-temperature filtration, tar removal, desulfurization, and removal of halides and nitrogen species, are evaluated with emphasis on integrated systems. Emerging approaches such as novel catalysts and sorbents, as well as advanced strategies like molten-salt-based gasification or cleaning, are also reviewed. Recent advances in process modeling, including kinetic and equilibrium models, Aspen Plus simulations, and physics-informed machine learning, are highlighted for optimizing gasification-cleaning chains. Additionally, a decision-tree flowchart is proposed to guide the selection of appropriate gas-cleaning strategies for efficient methanol production. The review shows that integrated cleaning strategies tailored to gasifier type, combined with advanced modeling tools, have strong potential to reduce purification costs and improve the economic feasibility of methanol synthesis from biomass and waste.