Survival Threshold Research Articles

Identifying stream temperature variation by coupling meteorological, hydrological, and water temperature models

AbstractIn this study, we demonstrate a physically based semi‐Lagrangian water temperature model known as the River Basin Model (RBM) coupled with the Variable Infiltration Capacity (VIC) hydrological model and Weather Research & Forecasting Model in the Mississippi River Basin (MRB). The results of this coupling compare favorably with observed water temperature data available from six river gages located in the MRB. Further sensitivity analysis indicates that the mean water temperatures may increase by 1.3, 1.5, and 1.8°C in northern, central, and southern MRB zones under a hypothetical uniform air temperature increase of 3.0°C. If air temperatures increase uniformly by 6.0°C in this scenario, then water temperatures are projected to increase by 3.3, 3.5, and 4.0°C. Lastly, downscaled air temperatures from a global climate model are used to drive the coupled VIC and RBM model from 2020 to 2099. Average stream temperatures from 2020 to 2099 increase by 1.0 to 8.0°C above 1950 to 2010 average water temperatures, with non‐uniform increases along the river. In some portions of the MRB, stream temperatures could increase above survival thresholds for several native fish species, which are critical components of the stream ecosystem. In addition, increased water temperatures interact with nutrient loadings from sources throughout the MRB, which is expected to exacerbate harmful algal blooms and dead zones in the Gulf of Mexico.

Post Salvage Therapy Autologous Transplant for Relapsed Myeloma, Ongoing Relevance within Modern Treatment Paradigms?

Salvage transplant has been historically considered effective therapy for myeloma patients relapsing after first transplant, if they achieved adequate remission duration. However, the efficacy of novel agent combinations has called this paradigm into question. We performed a retrospective analysis in a homogeneously treated cohort of 106 patients undergoing ASCT2 at our institution, all of whom received novel agent-based chemotherapy (immunomodulatory agent [IMiD] and/or proteasome inhibitor [PI]) for both induction and relapse. As an exploratory objective we assessed whether predictive thresholds of progression free survival post first transplant (ASCT1) for benefit post ASCT2 vary with use of IMiD maintenance post ASCT1. The overall response rate (ORR) was 98% post-ASCT2 and treatment-related mortality (TRM) was low at 1.8%. With a median follow-up of 26 months (range 0.5-85) from ASCT2, median overall survival (OS) is estimated at 80 months (95% CI: ≥ 49-months) and median progression-free survival after ASCT2 (PFS2) at 24 months (95% CI 19-39). PFS post first transplant (PFS1) at >/= 50 months was associated with improved OS. Predictors of PFS2 included PFS1 ≤42 months and progression on IMiD-based maintenance post- ASCT1. ASCT2 continues to offer acceptable outcomes for most patients treated within modern day treatment paradigms, with longer PFS after ASCT1 and IMiD non-refractory disease being associated with improved outcomes.

Cloudy with a chance of rain: accretion braking of cold clouds

ABSTRACT Understanding the survival, growth, and dynamics of cold gas is fundamental to galaxy formation. While there has been a plethora of work on ‘wind tunnel’ simulations that study such cold gas in winds, the infall of this gas under gravity is at least equally important, and fundamentally different since cold gas can never entrain. Instead, velocity shear increases and remains unrelenting. If these clouds are growing, they can experience a drag force due to the accretion of low-momentum gas, which dominates over ram pressure drag. This leads to subvirial terminal velocities, in line with observations. We develop simple analytic theory and predictions based on turbulent radiative mixing layers. We test these scalings in 3D hydrodynamic simulations, both for an artificial constant background and a more realistic stratified background. We find that the survival criterion for infalling gas is more stringent than in a wind, requiring that clouds grow faster than they are destroyed ($t_{\rm grow} \lt 4\, t_{\rm cc}$). This can be translated to a critical pressure, which for Milky Way-like conditions is $P \sim 3000 \, {k}_\mathrm{ B} \, {\rm K}\, {\rm cm}^{-3}$. Cold gas that forms via linear thermal instability (tcool/tff < 1) in planar geometry meets the survival threshold. In stratified environments, larger clouds need only survive infall until cooling becomes effective. We discuss applications to high-velocity clouds and filaments in galaxy clusters.

A Novel Lepidoptera bioassay analysed using a reduced GUTS model

Lepidopteran species can be both pests and also beneficial pollinators for agricultural crops. However, despite these important roles, the effects of pesticides on this diverse taxa are relatively understudied. To facilitate the assessment of pesticides and other chemical hazards on this taxa, we present a novel bioassay capable of testing chemical sensitivity to lepidopteran larvae through dietary exposure. We used Mamestra brassicae caterpillars as a model lepidopteran and tested their sensitivity for the organophosphate insecticide chlorpyrifos. We exposed larvae to an artificial diet spiked with chlorpyrifos and monitored survival over time, as well as weight change over a 96-hour exposure period. To test the repeatability and reliability of the developed bioassay, the experiment was repeated three times. The survival in time data collected enabled analysis with the General Unified Threshold of Survival (GUTS) model, recently recognized by EFSA as a ready-to-use tool for regulatory purposes. The GUTS modelling was used to derive a set of relevant toxicokinetic and toxicodynamic parameters relating to the larval response to exposure over time. We found that across the three repeats studies there was no more than a threefold difference in LC₅₀ values (13.1, 18.7 and 8.1 mg/Kg) at 48 h and fourfold difference at 96 h, highlighting the repeatability of the bioassay. We also highlighted the potential of the method to observe sub-lethal effects such as changes in weight. Finally, we discuss the applications of this new bioassay method to chemical risk assessments and its potential for use in other scenarios, such as mixture or pulsed exposure testing.

Studying Direct Lightning Stroke Impact on Human Safety Near HVTL Towers Considering Two Layer Soils and Ionization Influence

A lightning strike is considered one of the most risky natural phenomena that can lead to human harmful and the surrounding soil layers. To tackle this issue, this article investigates the influence of direct lightning characteristics in terms of human body safety. Specifically, such investigation is carried out on the effect of resistivities of two-layer soils on human safety when lightning stroke hits the towers of the high voltage transmission lines (HVTLs). The merit of the proposed study is that the soil ionization phenomenon is taken into consideration. Further, the study focuses on the current passing through the human heart, when step and touch (contact) voltages are generated by grounding potential rise, caused by direct lightning strikes transmission tower and the produced potential rise that a person could be exposed. Also, studying the effects of peak current and time of lightning strokes are investigated. Additionally, the paper presents the effect of different reflection factors on human safety. For validation purposes, the ATP program is used in the simulation of the grounding system as well as the human body model. Numerous simulations were accomplished in order to examine the behavior of the current passing through with the human heart. Based on the simulation results, it was concluded that the soil characteristics have superior influences on the contact and step potentials and, accordingly, the survival threshold.

Neonatal and Obstetric Provider Perceptions and Management at 22 Weeks' Gestation.

Active treatment for periviable infants may be influenced by neonatal and obstetric provider perceptions of prognosis. The two aims of this study are to (1) quantify prognostic discordance between provider and data-driven survival estimates and (2) evaluate if prognostic discordance is associated with the threshold probability of survival at which neonatal providers recommend active treatment or obstetric providers recommend antenatal corticosteroids. Provider survival estimates and threshold probabilities of survival for active treatment and antenatal steroid use were obtained from a case-based survey for an infant or pregnancy at 22 weeks' gestation that was administered at two Atlanta hospitals. Data-driven survival estimates, including ranges, were acquired through the National Institute of Child Health and Human Development Extremely Preterm Birth Outcomes Tool. Prognostic discordance was calculated as the difference between a provider and data-driven estimates and classified as pessimistic (provider estimate below data-driven estimate range), accurate (within range), or optimistic (above range). The association between prognostic discordance and the threshold probability of survival was evaluated using nonparametric tests. We had 137 neonatal respondents (51% response rate) and 57 obstetric responses (23% response rate). The overall median prognostic discordance was 1.5% (interquartile range: 17, 13) and 52 (27%) of all respondents were pessimistic, 100 (52%) were accurate, and 42 (22%) were optimistic. The survival threshold above which neonatal and obstetric providers recommended active treatment or antenatal corticosteroids was 30% (20-45%) and 10% (0-20%), respectively. Thresholds did not significantly differ among the three prognostic discordance groups (p = 0.45 for neonatal and p = 0.53 for obstetric providers). There was also no significant correlation between the magnitude of prognostic discordance and thresholds. Prognostic discordance exists among both neonatal and obstetric providers. However, this discordance is not associated with the threshold probability of survival at which providers recommend active treatment or antenatal corticosteroids at 22 weeks' gestation. · Prognostic discordance at 22 weeks' gestation exists for neonatal and obstetric providers.. · Prognostic discordance is not associated with survival thresholds for neonatal active treatment.. · Prognostic discordance is not associated with survival thresholds for the use of antenatal corticosteroids..

Abstract B049: Comparison of keratin 17 and GATA6 as prognostic markers in pancreatic cancer

Abstract Background: Clinically and histologically identical pancreatic ductal adenocarcinomas (PDACs) differ in response to treatment, disease progression, and survival. Clinical trials are testing the use of either keratin 17 (K17) or GATA6 as surrogate prognostic and predictive biomarkers of PDAC. Still, there is a need to contrast their expression and prognostic value in the same cohort of cases. K17, a biomarker of the most aggressive subtype of PDAC, promotes tumor growth and chemoresistance. GATA6 is a transcription factor necessary for normal pancreatic development, and a surrogate marker of the classical subtype of PDAC, associated with longer-term survival. Our goal was to test the hypothesis that there is a reciprocal relationship between K17 and GATA6 expression and that their detection informs prognostic stratification. Methods: Stony Brook University Hospital PDAC patients were selected, and representative sections were processed for dual-staining by indirect immunoperoxidase methods using antibodies to K17 (KDx Diagnostics) and GATA6 (R&D Systems AF1700). Manual scoring of the proportion of cells with strong (2+) nuclear and/or cytoplasmic staining was determined for K17 versus nuclear staining for GATA6 (PathSQ). Automated image analysis of GATA6 expression was further scored using QuPath v0.3.2 on annotated PDAC sections. Cut-off values for the best COX model for each marker were established to stratify for survival. Results: K17 expression was observed in cancer epithelial cells and in few benign proliferative ducts of chronic pancreatitis but no staining was detected in stromal or acinar cells. By contrast, GATA6 was detected in the nuclei of most cancer epithelial cells and was also consistently detected in benign ductal cells, acinar cells, and stromal cells. Defining high K17 cases as those with staining in ≥10% of tumor cells, high K17 correlated with shorter overall survival (p=0.03), supporting its use as a negative prognostic biomarker. Due to the high level of expression of GATA6 in PDAC cells (range 60-100% of tumor cells across all cases), however, no threshold was found to provide prognostic value. By dual-color IHC, K17 positive cells almost always had strong GATA6 nuclear staining but GATA6 was also detected in all K17-negative tumor cells. Computational analysis demonstrated 98% concordance with manual scoring for high GATA6 and 90% concordance with manual scoring for low GATA6. Conclusions: GATA6 was expressed in most PDAC tumor cells, as well as in benign stromal and epithelial cells. However, K17 expression was focal, relatively tumor cell-specific, and was not detected in most benign cellular components. Although high K17 status identified cases with relatively short survival, a survival threshold for GATA6 could not be detected. Contradiction in our observations of GATA6 compared to previous reports could result from differences in case selection or immunohistochemical protocol. Thus, further work is needed to explore the relationship between K17 and GATA6 as complementary biomarkers of PDAC patient survival. Citation Format: Michael Horowitz, Lyanne Oblein, Jaymie Oentoro, Saumya Kasliwal, Natalia D. Marchenko, Luisa F. Escobar-Hoyos, Kenneth R. Shroyer. Comparison of keratin 17 and GATA6 as prognostic markers in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B049.

Developmental spontaneous activity promotes formation of sensory domains, frequency tuning and proper gain in central auditory circuits.

Neurons that process sensory information exhibit bursts of electrical activity during development, providing early training to circuits that will later encode similar features of the external world. In the mammalian auditory system, this intrinsically generated activity emerges from the cochlea prior to hearing onset, but its role in maturation of auditory circuitry remains poorly understood. We show that selective suppression of cochlear supporting cell spontaneous activity disrupts patterned burst firing of central auditory neurons without affecting cell survival or acoustic thresholds. However, neurons in the inferior colliculus of these mice exhibit enhanced acoustic sensitivity and broader frequency tuning, resulting in wider isofrequency laminae. Despite this enhanced neural responsiveness, total tone-responsive regions in the auditory cortex are substantially smaller. Thus, disruption of pre-hearing cochlear activity causes profound changes in neural encoding of sound, with important implications for restoration of hearing in individuals who experience reduced activity during this critical developmental period.

The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice.

Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice was associated with the failure in homeostasis restoration mediated by the cytokine interferon (IFN)-γ. Our findings show that diet composition calibrates host survival threshold by regulating adaptive homeostasis and highlights a pivotal role for extrinsic signals in host phenotype and outcome of host-pathogen interaction.

Identifying overall survival in 98 glioblastomas using VASARI features at 3T

PurposeThis study aims to evaluate qualitative and quantitative imaging metrics along with clinical features affecting overall survival in glioblastomas and to classify them into high survival and low survival groups based on 12, 19, and 24 months thresholds using machine learning. MethodsThe cohort consisted of 98 adult glioblastomas. A standard brain tumor magnetic resonance (MR) imaging protocol, was performed on a 3T MR scanner. Visually Accessible REMBRANDT Images (VASARI) features were assessed. A Kaplan-Meier survival analysis followed by a log-rank test and multivariate Cox regression analysis were used to investigate the effects of VASARI features along with the age, gender, the extent of resection, pre- and post-KPS, ki67 and P53 mutation status on overall survival. Supervised machine learning algorithms were employed to predict the survival of glioblastoma patients based on 12, 19, and 24 months thresholds. ResultsTumor location (p<0.001), the proportion of non-enhancing component (p=0.0482), and proportion of necrosis (p=0.02) were significantly associated with overall survival based on Kaplan-Meier analysis. Multivariate Cox regression analysis revealed that increases in proportion of non-enhancing component (p=0.040) and proportion of necrosis (p=0.039) were significantly associated with overall survival. Machine-learning models were successful in differentiating patients living longer than 12 months with 96.40% accuracy (sensitivity=97.22%, specificity=95.55%). The classification accuracies based on 19 and 24 months survival thresholds were 70.87% (sensitivity=83.02%, specificity=60.11%) and 74.66% (sensitivity=67.58%, specificity=82.08%), respectively. ConclusionEmploying clinical and VASARI features together resulted in a successful classification of glioblastomas that would have a longer overall survival.

Effects of Desiccation and Freezing on Microbial Ionizing Radiation Survivability: Considerations for Mars Sample Return.

Increasingly, national space agencies are expanding their goals to include Mars exploration with sample return. To better protect Earth and its biosphere from potential extraterrestrial sources of contamination, as set forth in the Outer Space Treaty of 1967, international efforts to develop planetary protection measures strive to understand the danger of cross-contamination processes in Mars sample return missions. We aim to better understand the impact of the martian surface on microbial dormancy and survivability. Radiation resistance of microbes is a key parameter in considering survivability of microbes over geologic times on the frigid, arid surface of Mars that is bombarded by solar and galactic cosmic radiation. We tested the influence of desiccation and freezing on the ionizing radiation survival of six model microorganisms: vegetative cells of two bacteria (Deinococcus radiodurans, Escherichia coli) and a strain of budding yeast (Saccharomyces cerevisiae); and vegetative cells and endospores of three Bacillus bacteria (B. subtilis, B. megaterium, B. thuringiensis). Desiccation and freezing greatly increased radiation survival of vegetative polyploid microorganisms when applied separately, and when combined, desiccation and freezing increased radiation survival even more so. Thus, the radiation survival threshold of polyploid D. radiodurans cells can be extended from the already high value of 25 kGy in liquid culture to an astonishing 140 kGy when the cells are both desiccated and frozen. However, such synergistic radioprotective effects of desiccation and freezing were not observed in monogenomic or digenomic Bacillus cells and endospores, which are generally sterilized by 12 kGy. This difference is associated with a critical requirement for survivability under radiation, that is, repair of genome damage caused by radiation. Deinococcus radiodurans and S. cerevisiae accumulate similarly high levels of the Mn antioxidants that are required for extreme radiation resistance, as do endospores, though they greatly exceed spores in radioresistance because they contain multiple identical genome copies, which in D. radiodurans are joined by persistent Holliday junctions. We estimate ionizing radiation survival limits of polyploid DNA-based life-forms to be hundreds of millions of years of background radiation while buried in the martian subsurface. Our findings imply that forward contamination of Mars will essentially be permanent, and backward contamination is a possibility if life ever existed on Mars.

The effects of different temperatures in mercury toxicity to the terrestrial isopod Porcellionides pruinosus

Climate changes and metal contamination are pervasive stressors for soil ecosystems. Mercury (Hg), one of the most toxic metals, has been reported to interact with temperature. However, compared to aquatic biota, little is known about how temperature affects Hg toxicity and bioaccumulation to soil organisms. Here, toxicity and bioaccumulation experiments were replicated at 15 °C, 20 °C, and 25 °C to understand how sub-optimal temperatures affect the toxicokinetics and toxicodynamics of Hg via soil. Genotoxicity and energy reserves were also assessed to disclose potential trade-offs in life-history traits. Results underpin the complexity of temperature-Hg interactions. Survival was determined mainly by toxicokinetics, but toxicodynamics also played a significant role in defining survival probability during early stages. The processes determining survival probability were faster at 25 °C: General Unified Threshold of Survival (GUTS) model identified an earlier/steeper decline in survival, compared to 20 °C or 15 °C, but it also approached the threshold faster. Despite potentiation of Hg genotoxicity, temperature promoted faster detoxification, either increasing toxicokinetics rates or damage repair mechanisms. This metabolism-driven increase in detoxification led to higher depletion of energy reserves and likely triggered stress response pathways. This work emphasized the need for comprehensive experimental approaches that can integrate the multiple processes involved in temperature-metal interactions.

Reef on the edge: resilience failure of marginal patch coral reefs in Eastern Arabian Sea under recurrent coral bleaching, coral diseases, and local stressors.

Marked by strong El Niño-Southern Oscillation (ENSO) effects during 2014-2016, global coral reefs underwent mass bleaching. Here, we conducted a comprehensive (2014-2019) study, coinciding with the 2014-16 ENSO, to investigate the response and resilience potential of marginal coral communities to the combined impact of recurrent thermal anomalies and multiple anthropogenic stressors before, during, and after the mass bleaching episodes. Our result unveiled that thermal-stress-driven back-to-back annual coral bleaching episodes caused coral mortality and significantly decimated coral cover, primarily in 2015 and 2016. Subsequent benthic regime shifts toward macroalgal and algal turf colonization, followed by an increase in coral disease prevalence and recruitment failure wasobserved after the recurrent bleaching episodes. Algal cover increased from 21% in 2014 to 52.90% in 2019, and a subsequent increase in coral disease occurrence was observed from 16% in 2015 to 29% in 2019. The cascading negative effect of multiple stressors magnified coral loss and decreased the coral cover significantly from 45% in 2014 to 20% in 2019. The corals in the intensive recreational diving activity sites showed higher disease prevalence, concurring with high mechanical coral damage. The present study demonstrates that consecutive thermal bleaching episodes combined with local stressors can cause declines in coral cover and promote an undesirable regime shift to algal dominance in marginal coral reef habitats within a short duration. These results are of particular interest given that marginal reefs were traditionally perceived as resilient reef habitats due to their higher survival threshold to environmental changes. The present study indicates that mitigation of local stressors by effective management strategies, in conjunction with globally coordinated efforts to ameliorate climate change, can protect these unique coral reefs.

Defining clinically important overall survival thresholds: lessons from quality of life.

Defining clinically important overall survival thresholds: lessons from quality of life.

Quantitative Analysis of the MGMT Methylation Status of Glioblastomas in Light of the 2021 WHO Classification.

Simple SummaryThe status of a DNA repair protein called MGMT is a prognostic marker in patients with glioblastomas, the most frequent malignant brain tumor. Epigenetic silencing of this gene predicts increased sensitivity to chemotherapy. Silencing is assessed by analyzing modifications, so-called methylation, of a certain gene region. Whereas most studies report such information only in a qualitative manner, quantitative testing might provide additional information. The aim of our study was to determine a quantitative threshold for better survival among patients with glioblastomas. Among 321 patients suffering from glioblastoma, we found better survival in patients with glioblastomas that have ≥16% methylation of a particular region of the MGMT gene. Above 16% methylation, we found no additional benefit with increasing degree of methylation. We suggest using this threshold for selection in clinical trials and for patient counseling.Background: Glioblastomas with methylation of the promoter region of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene exhibit increased sensitivity to alkylating chemotherapy. Quantitative assessment of the MGMT promoter methylation status might provide additional prognostic information. The aim of our study was to determine a quantitative methylation threshold for better survival among patients with glioblastomas. Methods: We included consecutive patients ≥18 years treated at our department between 11/2010 and 08/2018 for a glioblastoma, IDH wildtype, undergoing quantitative MGMT promoter methylation analysis. The primary endpoint was overall survival. Results: A total of 321 patients were included. Median overall survival was 12.6 months. Kaplan–Meier and adjusted Cox regression analysis showed better survival for the groups with 16–30%, 31–60%, and 61–100% methylation. In contrast, survival in the group with 1–15% methylation was similar to those with unmethylated promoter regions. A secondary analysis confirmed this threshold. Conclusions: Better survival is observed in patients with glioblastomas with ≥16% methylation of the MGMT promoter region than with <16% methylation. Survival with tumors with 1–15% methylation is similar to with unmethylated tumors. Above 16% methylation, we found no additional benefit with increasing methylation.

Development and Verify of Survival Analysis Models for Chinese Patients With Systemic Lupus Erythematosus

BackgroundThe aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status.MethodsIn this study, based on 1999–2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients’ survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression.ResultsThe overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment.ConclusionsThe proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.

Comparison of ammonia thresholds for survival and reproduction between two copepods: The planktonic calanoid Eurytemora affinis and the benthic harpacticoid Tigriopus japonicus

The planktonic species Eurytemora affinis and the benthic species Tigriopus japonicus are two copepods that are extensively employed in aquaculture operations, especially as a source of live feed during larval rearing. Compared to T. japonicus, E. affinis is difficult to keep in stable cultures and to mass produce, which largely limits its usage. Furthermore, high levels of un-ionized ammonia (NH3−N) can limit the productivity of aquatic organisms. However, the toxicity of NH3-N can be easily affected by environmental conditions. The planktonic and benthic growth features of E. affinis and T. japonicus may reflect different adaptations to NH3−N stress that could affect their reproductive performances. Hence, we investigated the effect of NH3−N on the survival and reproductive patterns of E. affinis and T. japonicus at both the individual and population levels. The median lethal concentrations for both the nauplius and copepodite stages, life history parameters, and population growths of each species were evaluated after acute (24-h) and chronic (21–28 days) NH3−N exposure. The results showed that E. affinis was more vulnerable to NH3−N stress than T. japonicus at all developmental stages. The nauplius and copepodite stages of E. affinis exhibited 14.7- and 33.7-fold lower 24-h LC50 doses, respectively, than those of T. japonicus. Chronic individual exposure to NH3−N concentrations over a specific threshold (≥ 0.2 mg/L for E. affinis and ≥ 14.6 mg/L for T. japonicus) affected survival rates, extended the duration of the nauplius and copepodite stages, and delayed maturation in both species. In contrast, batch culture showed that low concentrations of NH3−N were beneficial to the reproduction of T. japonicus, whereas such a trend was not clearly observed in E. affinis. Finally, we hypothesize that the differences in the NH3−N sensitivities of E. affinis and T. japonicus could be attributed to their evolutionary history in pelagic and benthic habitats, respectively. The low NH3−N tolerance of E. affinis indicates the importance of managing ammonia levels during their cultivation.

A Song of Wind and Ice: Increased Frequency of Marine Cold‐Spells in Southwestern Patagonia and Their Possible Effects on Giant Kelp Forests

AbstractIn contrast to other coastal regions of the world, the giant kelp (Macrocystis pyrifera) ecosystem in southwestern Patagonia has been persistent in area and associated biodiversity in the last decades. In this ecoregion, sea surface temperature (SST) records have consistently remained below the upper thermal threshold for kelp survival, however, no studies have analyzed the spatiotemporal variability of SSTs and their anomalies across the geographical diversity of the southwestern Patagonian coastline. We explored the geographical distribution of extreme warm and cold events in this region from latitudes 47°–56°S in a range of ∼1,000 km, identifying the dates and spatial distribution of marine heatwaves (MHWs) and marine cold‐spells (MCSs) from 1982 to 2020. Results show that a peak in the number of MHWs occurred in the great El Niño year of 1998. Additionally, the 2014–2019 period has had more severe and extreme MCSs than the previous decades. We discuss the origin of these events with a focus on three main processes: (a) geographically constrained cold events caused by glacier melting, (b) regional cold events caused by extreme winds linked to the position of the polar front, and (c) extensive SST anomalies linked to planetary‐scale events such as El Niño and La Niña. Overall, those processes were conductive to counteract global warming trends locally/regionally, highlighting southwestern Patagonia as a possible climatic refugium for the giant kelp ecosystem. Despite this, the effects of freshwater inputs and storm turbulence on the exposed coasts facing the Southern Ocean may cause new kinds of stress on this ecosystem.

Determiningoptimal donor heart ischemic times in adult cardiac transplantation.

ObjectivesUnsupervised statistical determination of optimal allograft ischemic time (IT) on heart transplant outcomes among ABO donor heart types.MethodsWe identified 36,145 heart transplants (2000–2018) from the United Network for Organ Sharing database. Continuous and categorical variables were analyzed with parametric and nonparametric testing. Determination of IT cutoffs for survival analysis was performed using Contal and O'Quigley univariable method and Vito Muggeo multivariable segmented modeling.ResultsUnivariable and multivariable IT threshold determination revealed a cutoff at about 3 h. The hourly increase in survival risk with ≥3 h IT is asymmetrically experienced at the early 90 days (hazard ratio [HR] = 1.29, p < .001) and up to 1‐year time point (HR = 1.16, p < .001). Beyond 1 year the risk of prolonged IT is less impactful (HR = 1.04, p = .022). Longer IT was associated with more postoperative complications such as stroke (2.7% vs. 2.3, p = .042), dialysis (11.6% vs. 9.1%, p < .001) and death from primary graft dysfunction (1.8% vs. 1.2%, p < .001). O blood type donor hearts with IT ≥ 3 h has significantly increased hourly mortality risk at 90 days (HR = 1.27, p < .001), 90 days to 1 year (HR = 1.22, p < .001) and >1 year (HR = 1.05, p = .041). For non‐O blood types with ≥3 h IT hourly mortality risk was increased at 90 days (HR = 1.33, p < .001), but not at 90 days to 1 year (HR = 1.09, p = .146) nor ≥1 year (HR = 1.08, p = .237).ConclusionsThe donor heart IT threshold for survival determined from unbiased statistical modeling occurs at 3 h. With longer preservation times, transplantation with O donor hearts was associated with worse survival.

A phase II multicenter trial assessing the efficacy and safety of first-line S-1 + ramucirumab in elderly patients with advanced/recurrent gastric cancer: KSCC1701

BackgroundThe mainstream first-line chemotherapy for advanced/recurrent gastric cancer (ARGC) is combination therapy including platinum-based agents. With the progressive aging of the society, the incidence of gastric cancer in elderly patients is increasing. However, elderly patients cannot tolerate these agents because of renal dysfunction or low quality of life. The KSCC1701 study explored the efficacy and safety of S-1 + ramucirumab in elderly patients with ARGC. Patients and methodsChemotherapy-naive patients aged ≥70 years with ARGC were eligible. Patients received S-1 (40–60 mg twice daily for 4 weeks in 6-week cycles) and ramucirumab (8 mg/kg every 2 weeks) until disease progression. The primary end-point was the 1-year overall survival (OS) rate. The anticipated lower threshold of 1-year survival was set at 40% in light of previous S-1–based regimens. The secondary end-points included progression-free survival (PFS), OS, the overall response rate (ORR) and safety. ResultsBetween September 2017 and November 2019, 48 patients (34 men and 14 women) were enrolled in this study. The median patient age was 77.5 years, and all patients had a performance status of 0 (n = 20) or 1 (n = 28). The 1-year OS rate was 65.2%, which met the primary end-point. The median survival time and median PFS were 16.4 and 5.8 months, respectively. The ORR was 41.9%. The most frequent grade 3/4 (≥15%) adverse events were neutropenia, anorexia and anaemia. ConclusionConsidering these findings, S-1 + ramucirumab appears to be an excellent treatment option for elderly patients with ARGC. (250 words).This trial has been registered with the Japan Registry of Clinical Trials Registry under the number jRCTs071180066.