The potential of indocyanine green fluorescence detection in surgical cut margin of breast conserving surgery.

Background: Fluorescence-guided surgery (FGS) is a cutting-edge technology that uses near-infrared (NIR) fluorescence imaging to guide surgeons in surgery. Indocyanine green (ICG) is a fluorescent dye, which can be used for in vivo imaging of tumor cells. We aimed to explore the use of ICG fluorescence-guided technology as a rapid intraoperative margin assessment method for breast cancer surgery. In addition, we also compared the dose selection of ICG. Methods: This was a non-randomized prospective cohort study. Data were collected between August 2021 and October 2022 in the Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University. Upon specimen removal, tumor margins were immediately analyzed by ICG fluorescence detection and then sent to the pathology department for intraoperative frozen section analysis and subsequent routine pathological examination. Abnormal margin rates were calculated and compared using intraoperative frozen section analysis and under the guidance of ICG fluorescence. Results: The study included 69 cases of breast cancer patients who underwent tumor resection assisted by ICG fluorescence-guided technology, including 18 patients with a 0.5 mg/kg dose and 51 patients with a 1.0 mg/kg dose. According to the study findings, the ICG test achieved a sensitivity of 81.82% and a specificity of 75.82%. At a dose of 0.5 mg/kg, the sensitivity was 66.67% whereas the specificity was 93.33%. At the dose of 1 mg/kg, the sensitivity was 87.5%, and the specificity was 74.42%. Similarly, for intraoperative frozen section analysis, the sensitivity was 81.82%, but the specificity was enhanced to 94.83%. Positive surgical cut margin was not identified in 2/69 by ICG fluorescence and frozen section analysis respectively. Conclusions: The sensitivity of ICG fluorescence detection is comparable to that of frozen section analysis, but the specificity is poor. The sensitivity increased and the specificity decreased at 1 mg/kg compared to the 0.5 mg/kg dose. ICG fluorescence can be used as a supplementary tool for frozen section analysis. These findings support further development and clinical performance assessment of ICG fluorescence.

Meta-analysis application to hERG safety evaluation in clinical trials.

One objective of meta-analysis, which synthesizes evidence across multiple studies, is to assess the consistency and investigate the heterogeneity across studies. In this project, we performed a meta-analysis on moxifloxacin (positive control in QT assessment studies) data to characterize the exposure-response relationship and determine the safety margin associated with 10-msec QTc effects for moxifloxacin based on 26 thorough QT studies submitted to the FDA. Multiple meta-analysis methods were used (including two novel methods) to evaluate the exposure-response relationship and estimate the critical concentration and the corresponding confidence interval of moxifloxacin associated with a 10-msec QTc effect based on the concentration-QTc models. These meta-analysis methods (aggregate data vs. individual participant data; fixed effect vs. random effect) were compared in terms of their precision and robustness. With the selected meta-analysis method, we demonstrated the homogeneity and heterogeneity of the moxifloxacin concentration-QTc relationship in studies. We also estimated the critical concentration of moxifloxacin that can be used to calculate the hERG safety margin of this drug.

Supporting an integrated QTc risk assessment using the hERG margin distributions for three positive control agents derived from multiple laboratories and on multiple occasions.

BACKGROUND: Determination of a drug's potency in blocking the hERG channel is an established safety pharmacology study. Best practice guidelines have been published for reliable assessment of hERG potency. In addition, a set of plasma concentration and plasma protein binding fraction data were provided as denominators for margin calculations. The aims of the current analysis were five-fold: provide data allowing creation of consistent denominators for the hERG margin distributions of the key reference agents, explore the variation in hERG margins within and across laboratories, provide a hERG margin to 10 ms QTc prolongation based on several newer studies, provide information to use these analyses for reference purposes, and provide recommended hERG margin 'cut-off' values. METHODS: The analyses used 12 hERG IC50 'best practice' data sets (for the 3 reference agents). A group of 5 data sets came from a single laboratory. The other 7 data sets were collected by 6 different laboratories. RESULTS: The denominator exposure distributions were consistent with the ICH E14/S7B Training Materials. The inter-occasion and inter-laboratory variability in hERG IC50 values were comparable. Inter-drug differences were most important in determining the pooled margin variability. The combined data provided a robust hERG margin reference based on best practice guidelines and consistent exposure denominators. The sensitivity of hERG margin thresholds were consistent with the sensitivity described over the course of the last two decades. CONCLUSION: The current data provide further insight into the sensitivity of the 30-fold hERG margin 'cut-off' used for two decades. Using similar hERG assessments and these analyses, a future researcher can use a hERG margin threshold to support a negative QTc integrated risk assessment.

Lianas in tropical dry seasonal forests have a high hydraulic efficiency but not always a higher embolism resistance than lianas in rainforests.

BACKGROUND AND AIMS: Lianas have higher relative abundance and biomass in drier seasonal forests than in rainforests, but whether this difference is associated with their hydraulic strategies is unclear. Here, we investigate whether lianas of seasonally dry forests are safer and more efficient in water transport than rainforest lianas, explaining patterns of liana abundance. METHODS: We measured hydraulic traits on five pairs of congeneric lianas of the tribe Bignonieae in two contrasting forest sites: the wet 'Dense Ombrophilous Forest' in Central Amazonia (~2 dry months) and the drier 'Semideciduous Seasonal Forest' in the inland Atlantic Forest (~6 dry months). We also gathered a broader database, including 197 trees and 58 liana species from different tropical forests, to compare hydraulic safety between habits and forest types. KEY RESULTS: Bignonieae lianas from both forests had high and similar hydraulic efficiency but exhibited variability in resistance to embolism across forest types when phylogenetic relationships were taken into account. Three genera had higher hydraulic safety in the seasonal forest than in the rainforest, but species across both forests had similar positive hydraulic safety margins despite lower predawn water potential values of seasonal forest lianas. We did not find the safety-efficiency trade-off. Merging our results with previously published data revealed a high variability of resistance to embolism in both trees and lianas, independent of forest types. CONCLUSIONS: The high hydraulic efficiency of lianas detected here probably favours their rapid growth across tropical forests, but differences in hydraulic safety highlight that some species are highly vulnerable and may rely on other mechanisms to cope with drought. Future research on the lethal dehydration threshold and the connection between hydraulic resistance strategies and liana abundance could offer further insights into tropical forest dynamics under climatic threats.

Testing the shock protection performance of Type I construction helmets using impactors of different masses.

BACKGROUND: Wearing protective helmets is an important prevention strategy to reduce work-related traumatic brain injuries. The existing standardized testing systems are used for quality control and do not provide a quantitative measure of the helmet performance. OBJECTIVE: To analyze the failure characterizations of Type I industrial helmets and develop a generalized approach to quantify the shock absorption performance of Type I industrial helmets based on the existing standardized setups. METHODS: A representative basic Type I construction helmet model was selected for the study. Top impact tests were performed on the helmets at different drop heights using two different impactor masses (3.6 and 5.0 kg). RESULTS: When the helmets were impacted with potential impact energies smaller than the critical potential impact energy values, there was a consistent relationship between the peak impact force and the potential impact energy. When the helmets were impacted under potential impact energies greater than the critical potential impact energy values, the peak impact forces increased steeply with increasing potential impact energy. CONCLUSION: A concept of safety margin for construction helmets based on potential impact energy was introduced to quantify the helmets' shock absorption performance. The proposed method will help helmet manufacturers improve their product quality.

Rootstocks affect the vulnerability to embolism and pit membrane thickness in Citrus scions.

Embolism resistance of xylem tissue varies among species and is an important trait related to drought resistance, with anatomical attributes like pit membrane thickness playing an important role in avoiding embolism spread. Grafted Citrus trees are commonly grown in orchards, with the rootstock being able to affect the drought resistance of the whole plant. Here, we evaluated how rootstocks affect the vulnerability to embolism resistance of the scion using several rootstock/scion combinations. Scions of 'Tahiti' acid lime, 'Hamlin', 'Pera' and 'Valencia' oranges grafted on a 'Rangpur' lime rootstock exhibit similar vulnerability to embolism. In field-grown trees, measurements of leaf water potential did not suggest significant embolism formation during the dry season, while stomata of Citrus trees presented an isohydric response to declining water availability. When 'Valencia' orange scions were grafted on 'Rangpur' lime, 'IAC 1710' citrandarin, 'Sunki Tropical' mandarin or 'Swingle' citrumelo rootstocks, variation in intervessel pit membrane thickness of the scion was found. The 'Rangpur' lime rootstock, which is known for its drought resistance, induced thicker pit membranes in the scion, resulting in higher embolism resistance than the other rootstocks. Similarly, the rootstock 'IAC 1710' citrandarin generated increased embolism resistance of the scion, which is highly relevant for citriculture.

Coordinated hydraulic traits influence the two phases of time to hydraulic failure in five temperate tree species differing in stomatal stringency.

Worldwide, forests are increasingly exposed to extreme droughts causing tree mortality. Because of the complex nature of the mechanisms involved, various traits have been linked to tree drought responses with contrasting results. This may be due to species-specific strategies in regulating water potential, a process that unfolds in two distinct phases: a first phase until stomatal closure, and a second phase until reaching lethal xylem hydraulic thresholds. We conducted dry-down experiments with five broadleaved temperate tree species differing in their degree of isohydry to estimate the time to stomatal closure (tsc) and subsequent time to critical hydraulic failure (tcrit). We measured various traits linked to tree drought responses, such as the water potentials at turgor loss point (Ptlp), stomatal closure (Pgs90), and 12%, 50% and 88% loss of xylem hydraulic conductance (P12, P50, P88), hydraulic capacitance (C), minimum leaf conductance (gmin), hydroscape area (HSA) and hydraulic safety margins (HSM). We found that Pgs90 followed previously recorded patterns of isohydry and was associated with HSA. Species ranked from more to less isohydric in the sequence Acer pseudoplatanus < Betula pendula < Tilia cordata < Sorbus aucuparia < Fagus sylvatica. Their degree of isohydry was associated with leaf safety (Ptlp and gmin), drought avoidance (C) and tsc, but decoupled from xylem safety (HSM and P88) and tcrit. Regardless of their stomatal stringency, species with wider HSM and lower P88 reached critical hydraulic failure later. We conclude that the duration of the first phase is determined by stomatal regulation, while the duration of the second phase is associated with xylem safety. Isohydry is thus linked to water use rather than to drought survival strategies, confirming the proposed use of HSA as a complement to HSM for describing plant drought responses before and after stomatal closure.

Optimal temperature and thermal tolerance of postlarvae of the freshwater prawn Cryphiops (Cryphiops) caementarius acclimated to different temperatures.

In this study, the optimum temperature and thermal tolerance of postlarvae of the commercially important freshwater prawn Cryphiops (Cryphiops) caementarius were determined after acclimation to six different rearing temperatures (19 °C, 22 °C, 24 °C, 26 °C, 28 °C, and 30 °C) during a 45 day-culture period. Best growth parameter values were obtained within the temperature range of 24 °C to 28 °C, where the optimum temperature for growth was found to be at 26 °C (weight gain 81.70%; specific growth rate 1.33 %/day) but had not significant effect (p > 0.05) on survival (64%-71%) of postlarvae. Increasing the acclimation temperature significantly (p < 0.05) increased both the critical thermal maximum (CTMax: from 33.82 °C to 38.48 °C) and minimum (CTMin: from 9.27 °C to 14.58 °C). The thermal tolerance interval increased (p < 0.05) from 24.55 °C to 25.48 °C in postlarvae acclimated at 28 °C but decreased (p < 0.05) to 23.90 °C in those acclimated at 30 °C. The acclimation response rate was lower for CTMax and higher for CTMin. The current (12.48 °C) and future (9.48 °C) thermal safety margins were like those reported for other tropical crustaceans. A thermal tolerance polygon over the range of 19-30 °C resulted in a calculated area of 242.25 °C2. The presented results can be used for aquaculture activities and also to help to protect this species against expected climate warming impacts.

Review of the Terminology, Approaches, and Formulations Used in the Guidelines on Quantitative Risk Assessment of Chemical Hazards in Food.

This paper reviews the published terminology, mathematical models, and the possible approaches used to characterise the risk of foodborne chemical hazards, particularly pesticides, metals, mycotoxins, acrylamide, and polycyclic aromatic hydrocarbons (PAHs). The results confirmed the wide variability of the nomenclature used, e.g., 28 different ways of referencing exposure, 13 of cancer risk, or 9 of slope factor. On the other hand, a total of 16 equations were identified to formulate all the risk characterisation parameters of interest. Therefore, the present study proposes a terminology and formulation for some risk characterisation parameters based on the guidelines of international organisations and the literature review. The mathematical model used for non-genotoxic hazards is a ratio in all cases. However, the authors used the probability of cancer or different ratios, such as the margin of exposure (MOE) for genotoxic hazards. For each effect studied per hazard, the non-genotoxic effect was mostly studied in pesticides (79.73%), the genotoxic effect was mostly studied in PAHs (71.15%), and both effects were mainly studied in metals (59.4%). The authors of the works reviewed generally opted for a deterministic approach, although most of those who assessed the risk for mycotoxins or the ratio and risk for acrylamide used the probabilistic approach.

Utility of routine follow-up defibrillation safety margin testing in young patients with epicardial implantable cardioverter-defibrillators.

BACKGROUND: Routine defibrillation threshold testing (DFT) of transvenous implantable defibrillators (ICDs) has largely been in decline. In patients with non-transvenous ICDs that utilize subcutaneous and pleural ICD leads, serial DFT testing can detect a significant number of failures. Data about the utility of follow-up defibrillation safety margin testing (DSM) testing in pediatric patients and young adults with an epicardial ICD are lacking. METHODS: Patients aged < 25 years old who underwent epicardial ICD placement at Mayo Clinic from 2014 to 2023 with at least one follow-up DSM test were included. The patients were divided into a "routine" (R) and "clinically indicated" (CI) group based on the index of clinical concern. Inadequate DSM was defined as unsuccessful defibrillation at an output of less than 10 J below the maximum output of the device. The purpose of this study was to assess the utility of follow-up DSM testing. RESULTS: An epicardial ICD system was placed in 122 patients. A total of 26 patients met inclusion criteria and underwent a total of 47 DSM follow up tests. Inadequate DSM occurred in 1/33 (3%) in the R group and 2/14 (14%) DSM tests in the CI group. The median follow-up period was 54 and 36 months for the R and CI group, respectively. CONCLUSIONS: Our data suggest that epicardial ICDs are reliable and routine follow-up DSM testing may not be necessary for all patients. DSM testing should be performed in individuals with epicardial ICD systems when there is clinical concern about lead or coil performance.

Risk Factors for a Narrow Safety Margin after Endoscopic Submucosal Dissection for Early Gastric Cancer.

INTRODUCTION: A narrow safety margin (NSM) after endoscopic submucosal dissection (ESD) is a well-recognized risk factor for local recurrence in early gastric cancer (EGC). However, only a few studies have investigated the risk factors for the development of NSM. METHODS: The medical records and pathologic specimens of patients with EGC who underwent ESD from January 2020 to December 2020 at a single tertiary hospital (Daejeon, South Korea) were reviewed. RESULTS: A total of 218 patients were enrolled and 29 had NSM (<3 mm). When comparing the NSM and the control groups, the size of the lesion, the depth of invasion, and the operating endoscopist were found to be risk factors for the development of NSM. The increased length of the subepithelial spread of the lesion was associated with a narrower safety margin. Logistic regression analysis revealed that lesion size was a risk factor for NSM, and a marginally significant difference between endoscopists was found. CONCLUSIONS: Multiple factors may need to be considered during ESD, including lesion size, invasion depth, operating endoscopist, and subepithelial spread.

Vein hierarchy mediates the 2D relationship between leaf size and drought tolerance across subtropical forest tree species.

Previous studies have observed a 2D relationship (i.e. decoupled correlation) between leaf size (LS) and leaf economics as well as a tight correlation between leaf economics and drought tolerance. However, the underlying mechanism maintaining the relationship between LS and drought tolerance remains largely unknown. Here, we measured LS, water potential at 50% loss of hydraulic conductance, hydraulic safety margin and different orders of vein traits across 28 tree species in a subtropical forest in Southern China. We found that LS and drought tolerance were in two independent dimensions (R2 = 0.00, P > 0.05). Primary and secondary vein traits (i.e. vein diameter and density) explained the variation of LS, with R2 ranging from 0.37 to 0.70 (all Ps < 0.01), while minor vein traits accounted for the variation of leaf drought tolerance, with R2 ranging from 0.30 to 0.43 (all Ps < 0.01). Our results provide insight into the 2D relationship between LS and drought tolerance and highlight the importance of vein hierarchy in plant leaf functioning.

Plasticity in branch water relations and stem hydraulic vulnerability enhances hydraulic safety in mangroves growing along a salinity gradient.

Coping with water stress depends on maintaining cellular function and hydraulic conductance. Yet measurements of vulnerability to drought and salinity do not often focus on capacitance in branch organs that buffer hydraulic function during water stress. The relationships between branch water relations, stem hydraulic vulnerability and stem anatomy were investigated in two co-occurring mangroves Aegiceras corniculatum and Rhizophora stylosa growing at low and high salinity. The dynamics of branch water release acted to conserve water content in the stem at the expense of the foliage during extended drying. Hydraulic redistribution from the foliage to the stem increased stem relative water content by up to 21%. The water potentials at which 12% and 50% loss of stem hydraulic conductivity occurred decreased by ~1.7 MPa in both species between low and high salinity sites. These coordinated tissue adjustments increased hydraulic safety despite declining turgor safety margins at higher salinity sites. Our results highlight the complex interplay of plasticity in organ-level water relations with hydraulic vulnerability in the maintenance of stem hydraulic function in mangroves distributed along salinity gradients. These results emphasise the importance of combining water relations and hydraulic vulnerability parameters to understand vulnerability to water stress across the whole plant.

Evaluation of species thermal sensitivity with individual-based physiological performance.

Ignoring intraspecific variations can prevent us from accurately assessing species' thermal sensitivity to global warming. Individual-based physiological performance provides a feasible solution to depict species' thermal sensitivity using a bottom-up approach. We measured the cardiac performance of intertidal bivalves (1159 individuals from multiple populations of six bivalves), determined the upper thermal limit of each individual, calculated the proportions of individuals suffering sublethal/lethal heat stress, and mapped sensitive regions to high temperatures. Results showed that high inter-individual variations of physiological performance existed in levels of populations and species, and species' thermal sensitivity was positively related to the intraspecific variations of heat tolerance. This bottom-up approach scaled up from individual, population to species emphasizes the importance of individual-based physiology performance in assessing thermal sensitivity across different hierarchical levels and enables better evaluating and forecasting of species responses to global warming.

Rapid leaf xylem acclimation diminishes the chances of embolism in grapevines.

Under most conditions tight stomatal regulation in grapevines (Vitis vinifera) avoids xylem embolism. The current study evaluated grapevine responses to challenging scenarios that might lead to leaf embolism and consequential leaf damage. We hypothesized that embolism would occur if the vines experienced low xylem water potential (Ψx) shortly after bud break or later in the season under a combination of extreme drought and heat. We subjected vines to two potentially dangerous environments: (i) withholding irrigation from a vineyard grown in a heatwave-prone environment, and (ii) subjecting potted vines to terminal drought 1 month after bud break. In the field experiment, a heatwave at the beginning of August resulted in leaf temperatures over 45 °C. However, effective stomatal response maintained the xylem water potential (Ψx) well above the embolism threshold, and no leaf desiccation was observed. In the pot experiment, leaves of well-watered vines in May were relatively vulnerable to embolism with 50% embolism (P50) at -1.8 MPa. However, when exposed to drought, these leaves acclimated their leaf P50 by 0.65 MPa in less than a week and before reaching embolism values. When dried to embolizing Ψx, the leaf damage proportion matched (percentage-wise) the leaf embolism level. Our findings indicate that embolism and leaf damage are usually avoided by the grapevines' efficient stomatal regulation and rapid acclimation of their xylem vulnerability.

Drought survival in conifer species is related to the time required to cross the stomatal safety margin.

The regulation of water loss and the spread of xylem embolism have mostly been considered separately. The development of an integrated approach taking into account the temporal dynamics and relative contributions of these mechanisms to plant drought responses is urgently needed. Do conifer species native to mesic and xeric environments display different hydraulic strategies and temporal sequences under drought? A dry-down experiment was performed on seedlings of four conifer species differing in embolism resistance, from drought-sensitive to extremely drought-resistant species. A set of traits related to drought survival was measured, including turgor loss point, stomatal closure, minimum leaf conductance, and xylem embolism resistance. All species reached full stomatal closure before the onset of embolism, with all but the most drought-sensitive species presenting large stomatal safety margins, demonstrating that highly drought-resistant species do not keep their stomata open under drought conditions. Plant dry-down time to death was significantly influenced by the xylem embolism threshold, stomatal safety margin, and minimum leaf conductance, and was best explained by the newly introduced stomatal margin retention index (SMRIΨ50) which reflects the time required to cross the stomatal safety margin. The SMRIΨ50 may become a key tool for the characterization of interspecific drought survival variability in trees.

The Potential Mechanisms behind Loperamide-Induced Cardiac Arrhythmias Associated with Human Abuse and Extreme Overdose.

Loperamide has been a safe and effective treatment for diarrhea for many years. However, many cases of cardiotoxicity with intentional abuse of loperamide ingestion have recently been reported. We evaluated loperamide in in vitro and in vivo cardiac safety models to understand the mechanisms for this cardiotoxicity. Loperamide slowed conduction (QRS-duration) starting at 0.3 µM [~1200-fold (×) its human Free Therapeutic Plasma Concentration; FTPC] and reduced the QT-interval and caused cardiac arrhythmias starting at 3 µM (~12,000× FTPC) in an isolated rabbit ventricular-wedge model. Loperamide also slowed conduction and elicited Type II/III A-V block in anesthetized guinea pigs at overdose exposures of 879× and 3802× FTPC. In ion-channel studies, loperamide inhibited hERG (IKr), INa, and ICa currents with IC50 values of 0.390 µM, 0.526 µM, and 4.091 µM, respectively (i.e., >1560× FTPC). Additionally, in silico trials in human ventricular action potential models based on these IC50s confirmed that loperamide has large safety margins at therapeutic exposures (≤600× FTPC) and confirmed repolarization abnormalities in the case of extreme doses of loperamide. The studies confirmed the large safety margin for the therapeutic use of loperamide but revealed that at the extreme exposure levels observed in human overdose, loperamide can cause a combination of conduction slowing and alterations in repolarization time, resulting in cardiac proarrhythmia. Loperamide's inhibition of the INa channel and hERG-mediated IKr are the most likely basis for this cardiac electrophysiological toxicity at overdose exposures. The cardiac toxic effects of loperamide at the overdoses could be aggravated by co-medication with other drug(s) causing ion channel inhibition.

Surgical margin status and role of adjuvant therapy in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: We analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A total of 279 patients with HPV+ OPSCC were included in this study. RESULTS: Surgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1-5, and >5 mm. There was no significant difference in local-regional recurrence for T1-T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors. CONCLUSIONS: In T1-T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.

Long-term forecast of thermal mortality with climate warming in riverine amphipods.

Forecasting long-term consequences of global warming requires knowledge on thermal mortality and how heat stress interacts with other environmental stressors on different timescales. Here, we describe a flexible analytical framework to forecast mortality risks by combining laboratory measurements on tolerance and field temperature records. Our framework incorporates physiological acclimation effects, temporal scale differences and the ecological reality of fluctuations in temperature, and other factors such as oxygen. As a proof of concept, we investigated the heat tolerance of amphipods Dikerogammarus villosus and Echinogammarus trichiatus in the river Waal, the Netherlands. These organisms were acclimated to different temperatures and oxygen levels. By integrating experimental data with high-resolution field data, we derived the daily heat mortality probabilities for each species under different oxygen levels, considering current temperatures as well as 1 and 2°C warming scenarios. By expressing heat stress as a mortality probability rather than a upper critical temperature, these can be used to calculate cumulative annual mortality, allowing the scaling up from individuals to populations. Our findings indicate a substantial increase in annual mortality over the coming decades, driven by projected increases in summer temperatures. Thermal acclimation and adequate oxygenation improved heat tolerance and their effects were magnified on longer timescales. Consequently, acclimation effects appear to be more effective than previously recognized and crucial for persistence under current temperatures. However, even in the best-case scenario, mortality of D. villosus is expected to approach 100% by 2100, while E. trichiatus appears to be less vulnerable with mortality increasing to 60%. Similarly, mortality risks vary spatially: In southern, warmer rivers, riverine animals will need to shift from the main channel toward the cooler head waters to avoid thermal mortality. Overall, this framework generates high-resolution forecasts on how rising temperatures, in combination with other environmental stressors such as hypoxia, impact ecological communities.

Germination temperature sensitivity differs between co-occurring tree species and climate origins resulting in contrasting vulnerability to global warming.

Climate change is shifting temperatures from historical patterns, globally impacting forest composition and resilience. Seed germination is temperature-sensitive, making the persistence of populations and colonization of available habitats vulnerable to warming. This study assessed germination response to temperature in foundation trees in south-western Australia's Mediterranean-type climate forests (Eucalyptus marginata (jarrah) and Corymbia calophylla (marri)) to estimate the thermal niche and vulnerability among populations. Seeds from the species' entire distribution were collected from 12 co-occurring populations. Germination thermal niche was investigated using a thermal gradient plate (5-40°C). Five constant temperatures between 9 and 33°C were used to test how the germination niche (1) differs between species, (2) varies among populations, and (3) relates to the climate of origin. Germination response differed among species; jarrah had a lower optimal temperature and thermal limit than marri (T o 15.3°C, 21.2°C; ED50 23.4°C, 31°C, respectively). The thermal limit for germination differed among populations within both species, yet only marri showed evidence for adaptation to thermal origins. While marri has the capacity for germination at higher thermal temperatures, jarrah is more vulnerable to global warming exceeding safety margins. This discrepancy is predicted to alter species distributions and forest composition in the future.