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1.
Cognition ; 254: 105935, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260087

ABSTRACT

In human culture, an object's value is influenced by tangible properties (e.g. visual desirability and constituent materials) and intangible ownership history (e.g. authentic objects owned by celebrities are often worth more than similar inauthentic objects). Children are sensitive to both of these factors as independent determinants of value, but research has yet to elucidate how they interact. Here, we investigate whether children aged 5-11 years consider object properties or authentic ownership history to be the greater determinant of value and examine how their object valuations are influenced by owners' characteristics. In Study 1, visually desirable and undesirable items belonging to 'famously good' owners received higher valuations than similar items belonging to non-famous owners, whereas desirable items belonging to 'famously bad' owners received significantly lower values. In Study 2, children considered items made from cheap materials belonging to famously good owners, but not famously bad owners, to be as valuable as similar items made from expensive materials belonging to non-famous owners. In Study 3, physical contact with a famously bad owner had a detrimental impact on value, but worn and unworn objects belonging to famously good owners did not significantly differ in value. Across studies, we documented evidence that children's sensitivity to authentic ownership history and physical contact as determinants of value increases with age. Together, these findings demonstrate that children's valuation of ownership history relative to object properties depends on the owner's 'essence', and their sensitivity to owner contact as a mediator of value indicates awareness of 'magical contagion'.

2.
Cancers (Basel) ; 16(17)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39272789

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. METHODS: This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. RESULTS: In total, 331 patients with a median age of 74 years and male-female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I-III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09-6.34)] and urban residence (HR, 2.20; 95% CI, 1.1-4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85-4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51-4.62), lack of surgery (HR, 1.63; 95% CI, 1.03-2.57), a neutrophil-lymphocyte ratio of >3.2 (HR, 1.57; 1.05-2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04-2.19) were correlated with inferior overall survival. CONCLUSIONS: In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival.

3.
PLoS Pathog ; 20(6): e1012235, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843111

ABSTRACT

Amikacin and piperacillin/tazobactam are frequent antibiotic choices to treat bloodstream infection, which is commonly fatal and most often caused by bacteria from the family Enterobacterales. Here we show that two gene cassettes located side-by-side in and ancestral integron similar to In37 have been "harvested" by insertion sequence IS26 as a transposon that is widely disseminated among the Enterobacterales. This transposon encodes the enzymes AAC(6')-Ib-cr and OXA-1, reported, respectively, as amikacin and piperacillin/tazobactam resistance mechanisms. However, by studying bloodstream infection isolates from 769 patients from three hospitals serving a population of 1.2 million people in South West England, we show that increased enzyme production due to mutation in an IS26/In37-derived hybrid promoter or, more commonly, increased transposon copy number is required to simultaneously remove these two key therapeutic options; in many cases leaving only the last-resort antibiotic, meropenem. These findings may help improve the accuracy of predicting piperacillin/tazobactam treatment failure, allowing stratification of patients to receive meropenem or piperacillin/tazobactam, which may improve outcome and slow the emergence of meropenem resistance.


Subject(s)
Anti-Bacterial Agents , DNA Transposable Elements , Humans , Anti-Bacterial Agents/pharmacology , DNA Transposable Elements/genetics , Drug Resistance, Multiple, Bacterial/genetics , Piperacillin/pharmacology , Amikacin/pharmacology , Microbial Sensitivity Tests , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/genetics , Enterobacteriaceae/genetics , Enterobacteriaceae/drug effects , Integrons/genetics , Bacteremia/microbiology , Bacteremia/drug therapy , Bacteremia/genetics
4.
Proc Natl Acad Sci U S A ; 121(24): e2315700121, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38830099

ABSTRACT

Given the importance of climate in shaping species' geographic distributions, climate change poses an existential threat to biodiversity. Climate envelope modeling, the predominant approach used to quantify this threat, presumes that individuals in populations respond to climate variability and change according to species-level responses inferred from spatial occurrence data-such that individuals at the cool edge of a species' distribution should benefit from warming (the "leading edge"), whereas individuals at the warm edge should suffer (the "trailing edge"). Using 1,558 tree-ring time series of an aridland pine (Pinus edulis) collected at 977 locations across the species' distribution, we found that trees everywhere grow less in warmer-than-average and drier-than-average years. Ubiquitous negative temperature sensitivity indicates that individuals across the entire distribution should suffer with warming-the entire distribution is a trailing edge. Species-level responses to spatial climate variation are opposite in sign to individual-scale responses to time-varying climate for approximately half the species' distribution with respect to temperature and the majority of the species' distribution with respect to precipitation. These findings, added to evidence from the literature for scale-dependent climate responses in hundreds of species, suggest that correlative, equilibrium-based range forecasts may fail to accurately represent how individuals in populations will be impacted by changing climate. A scale-dependent view of the impact of climate change on biodiversity highlights the transient risk of extinction hidden inside climate envelope forecasts and the importance of evolution in rescuing species from extinction whenever local climate variability and change exceeds individual-scale climate tolerances.


Subject(s)
Climate Change , Extinction, Biological , Pinus , Pinus/physiology , Trees , Biodiversity , Forecasting/methods , Temperature , Climate Models
5.
Phys Rev Lett ; 132(13): 137401, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38613264

ABSTRACT

Adaptive transport networks are known to contain loops when subject to hydrodynamic fluctuations. However, fluctuations are no guarantee that a loop will form, as shown by loop-free networks driven by oscillating flows. We provide a complete stability analysis of the dynamical behavior of any loop formed by fluctuating flows. We find a threshold for loop stability that involves an interplay of geometric constraints and hydrodynamic forcing mapped to constant and fluctuating components. Loops require fluctuation in the relative size of the flux between nodes, not just a temporal variation in the flux at a given node. Hence, there is both a minimum and a maximum amount of fluctuation relative to the constant-flux component where loops are supported.

6.
Physiol Mini Rev ; 16(3): 22-34, 2023.
Article in English | MEDLINE | ID: mdl-38107545

ABSTRACT

Cardiac arrhythmias are associated with various forms of heart diseases. Ventricular arrhythmias present a significant risk for sudden cardiac death. Atrial fibrillations predispose to blood clots leading to stroke and heart attack. Scientists have been developing patch-clamp technology to study ion channels and action potentials (APs) underlying cardiac excitation and arrhythmias. Beyond the traditional patch-clamp techniques, innovative new techniques were developed for studying complex arrhythmia mechanisms. Here we review the recent development of methods including AP-Clamp, Dynamic Clamp, AP-Clamp Sequential Dissection, and Patch-Clamp-in-Gel. These methods provide powerful tools for researchers to decipher how the dynamic systems in excitation-Ca2+ signaling-contraction feedforward and feedback to control cardiac function and how their dysregulations lead to heart diseases.


Las arritmias cardiacas están asociadas a diferentes tipos de enfermedad cardiaca. Las arritmias ventriculares constituyen un alto riesgo de muerte súbita. La fibrilación auricular predispone a coágulos sanguíneos que pueden producir accidentes cerebrovasculares e infarto miocárdico. Los científicos han desarrollado la técnica de patch-clamp para estudiar los canales iónicos y los potenciales de acción (PAs), que constituyen la base de la excitación y las arritmias cardiacas. Además de las clásicas técnicas de patch-clamp, se desarrollaron técnicas innovativas para estudiar los mecanismos complejos de las arritmias. En este trabajo, describimos diferentes métodos recientemente desarrollados tales como AP-clamp ("clampeo" del PA), Dynamic Clamp ("clampeo" dinámico), AP-Clamp Sequential Dissection, (disección secuencial del "clampeo" del AP), y Patch-Clamp-in-Gel (Patch clamp en gel). Estos métodos constituyen herramientas poderosas para descifrar cómo los sistemas dinámicos que constituyen la excitación-las señales de Ca2+ y la contracción, se retroalimentan para controlar la función cardiaca y cómo sus alteraciones llevan a la enfermedad cardiaca.

7.
Pharmaceutics ; 15(8)2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37631382

ABSTRACT

AIM: The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport. METHODS: Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid along with either chitosan or pectin modification. bLf cellular uptake and transport were evaluated in vitro using the human adenocarcinoma cell line Caco-2 cell model. RESULTS AND DISCUSSION: The bLf-loaded SLPs showed no significant effect on cytotoxicity and did not induce apoptosis within the eight-hour investigation. The use of confocal laser scanning microscopy confirmed that bLf follows the receptor-mediated endocytosis, whereas the primary mechanism for the cellular uptake of SLPs was endocytosis. The bLf-loaded SLPs had significantly more cellular uptake compared to bLf alone, and it was observed that this impact varied based on the time, temperature, and concentration. Verapamil and EDTA were determined to raise the apparent permeability coefficients (App) of bLf and bLf-loaded SLPs. CONCLUSION: This occurred because they hindered efflux by interacting with P-glycoproteins and had a penetration-enhancing influence. These findings propose the possibility of an additional absorption mechanism for SLPs, potentially involving active transportation facilitated by the P-glycoprotein transporter in Caco-2 cells. These results suggest that SLPs have the potential to be applied as effective carriers to improve the oral bioavailability of proteins and peptides.

8.
Inhal Toxicol ; 35(7-8): 214-229, 2023.
Article in English | MEDLINE | ID: mdl-37339372

ABSTRACT

BACKGROUND: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. RESULTS: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. CONCLUSION: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.


Subject(s)
Asbestos, Amphibole , Asbestos , Rats , Animals , Asbestos, Amphibole/toxicity , Mineral Fibers , Aerosols , Inhalation Exposure/adverse effects
9.
Inhal Toxicol ; 35(7-8): 201-213, 2023.
Article in English | MEDLINE | ID: mdl-37339371

ABSTRACT

BACKGROUND: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. RESULTS: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically. CONCLUSIONS: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.


Subject(s)
Asbestos, Amphibole , Asbestos , Humans , Rats , Animals , Asbestos, Amphibole/toxicity , Mineral Fibers , Asbestos/analysis , Carcinogens/toxicity , Aerosols
10.
Glob Chang Biol ; 29(17): 4826-4841, 2023 09.
Article in English | MEDLINE | ID: mdl-37344959

ABSTRACT

Climate change-triggered forest die-off is an increasing threat to global forests and carbon sequestration but remains extremely challenging to predict. Tree growth resilience metrics have been proposed as measurable proxies of tree susceptibility to mortality. However, it remains unclear whether tree growth resilience can improve predictions of stand-level mortality. Here, we use an extensive tree-ring dataset collected at ~3000 permanent forest inventory plots, spanning 13 dominant species across the US Mountain West, where forests have experienced strong drought and extensive die-off has been observed in the past two decades, to test the hypothesis that tree growth resilience to drought can explain and improve predictions of observed stand-level mortality. We found substantial increases in growth variability and temporal autocorrelation as well declining drought resistance and resilience for a number of species over the second half of the 20th century. Declining resilience and low tree growth were strongly associated with cross- and within-species patterns of mortality. Resilience metrics had similar explicative power compared to climate and stand structure, but the covariance structure among predictors implied that the effect of tree resilience on mortality could partially be explained by stand and climate variables. We conclude that tree growth resilience offers highly valuable insights on tree physiology by integrating the effect of stressors on forest mortality but may have only moderate potential to improve large-scale projections of forest die-off under climate change.


Subject(s)
Forests , Trees , Droughts , Drought Resistance , Climate Change
11.
R Soc Open Sci ; 10(5): 221255, 2023 May.
Article in English | MEDLINE | ID: mdl-37206965

ABSTRACT

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students' understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship.

12.
Commun Psychol ; 1(1): 3, 2023 Jul 25.
Article in English | MEDLINE | ID: mdl-39242883

ABSTRACT

The emergence of large-scale replication projects yielding successful rates substantially lower than expected caused the behavioural, cognitive, and social sciences to experience a so-called 'replication crisis'. In this Perspective, we reframe this 'crisis' through the lens of a credibility revolution, focusing on positive structural, procedural and community-driven changes. Second, we outline a path to expand ongoing advances and improvements. The credibility revolution has been an impetus to several substantive changes which will have a positive, long-term impact on our research environment.

13.
iScience ; 25(9): 104810, 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36034223

ABSTRACT

[This corrects the article DOI: 10.1016/j.isci.2022.104667.].

14.
iScience ; 25(7): 104667, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35860762

ABSTRACT

The heart pumps blood into circulation against vascular resistance and actively regulates the contractile force to compensate for mechanical load changes. Our experimental data show that cardiomyocytes have a mechano-chemo-transduction (MCT) mechanism that increases intracellular Ca 2 + transient to enhance contractility in response to increased mechanical load. This study advances the cardiac excitation- Ca 2 + signaling-contraction (E-C) coupling model on conceptual and technical fronts. First, we developed analytical and computational models to perform 3-dimensional mechanical analysis of cardiomyocytes contracting in a viscoelastic medium under mechanical load. Next, we proposed an MCT feedback loop in the E-C coupling dynamic system to shift the feedforward paradigm of cardiac E-C coupling to an autoregulation model. Our combined modeling and experimental studies reveal that MCT enables autoregulation of E-C coupling and contractility in single cardiomyocytes, which underlies the heart's intrinsic autoregulation in compensatory response to load changes in order to maintain the stroke volume and cardiac output.

15.
Bioscience ; 72(3): 233-246, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35241971

ABSTRACT

Tree-ring time series provide long-term, annually resolved information on the growth of trees. When sampled in a systematic context, tree-ring data can be scaled to estimate the forest carbon capture and storage of landscapes, biomes, and-ultimately-the globe. A systematic effort to sample tree rings in national forest inventories would yield unprecedented temporal and spatial resolution of forest carbon dynamics and help resolve key scientific uncertainties, which we highlight in terms of evidence for forest greening (enhanced growth) versus browning (reduced growth, increased mortality). We describe jump-starting a tree-ring collection across the continent of North America, given the commitments of Canada, the United States, and Mexico to visit forest inventory plots, along with existing legacy collections. Failing to do so would be a missed opportunity to help chart an evidence-based path toward meeting national commitments to reduce net greenhouse gas emissions, urgently needed for climate stabilization and repair.

16.
PLoS One ; 17(2): e0263250, 2022.
Article in English | MEDLINE | ID: mdl-35108323

ABSTRACT

BACKGROUND: The current study aimed to determine the association between timing and completion of adjuvant chemotherapy and outcomes in real-world patients with early-stage pancreatic cancer. METHODS: In this multi-center cohort study patients with early-stage pancreatic cancer who were diagnosed from 2007-2017 and underwent complete resection in the province of Saskatchewan were examined. Cox proportional multivariate analyses were performed for correlation with recurrence and survival. RESULTS: Of 168 patients, 71 eligible patients with median age of 69 years and M:F of 37:34 were identified. Median time to the start of adjuvant therapy from surgery was 73 days. Of all patients, 49 (69%) patients completed adjuvant chemotherapy and 22 (31%) required early treatment discontinuation. Median recurrence-free survival of patients who completed treatment was 22 months (95%CI:15.8-28.2) vs. 9 months (3.3-14.7) if treatment was discontinued early (P<0.001). Median overall survival of those who completed treatment was 33 (17.5-48.5) vs. 16 months (17.5-48.5) with early treatment discontinuation (P<0.001). In the multivariate analysis, treatment discontinuation was significantly correlated with recurrent disease, hazard ratio (HR), 2.57 (1.41-4.68), P = 0.002 and inferior survival, HR, 2.55 (1.39-4.68), P = 0.003. No correlation between treatment timing and survival was noted. CONCLUSIONS: Early discontinuation but not the timing of adjuvant chemotherapy correlates with inferior outcomes.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/mortality , Neoplasm Recurrence, Local/mortality , Pancreatic Neoplasms/mortality , Withholding Treatment/statistics & numerical data , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Prognosis , Retrospective Studies , Survival Rate
17.
Can J Surg ; 65(1): E73-E81, 2022.
Article in English | MEDLINE | ID: mdl-35115320

ABSTRACT

BACKGROUND: Moving toward a funding standard similar to that for clinical services for roles essential to the functioning of education, research and leadership services within divisions of general surgery is necessary to strengthen divisional resilience. We aimed to identify roles and underlying tasks in these services central to sustainable functioning of Canadian academic divisions of general surgery. METHODS: Between June 2018 and October 2020, we used a 4-step modified Delphi method (online survey, face-to-face nominal group technique [n = 12], semistructured telephone interview [n = 8] and nominal group technique [n = 12]) to achieve national consensus from an expert panel of all 17 heads of academic divisions of general surgery in Canada on the roles and accompanying tasks essential to education, research and leadership services within an academic division of general surgery. We used 70% agreement to determine consensus. RESULTS: The expert panel agreed that a framework for role allocation in education, research and leadership services was relevant and necessary. Consensus was reached for 7 roles within the educational service, 3 roles within the research service and 5 roles within the leadership service. CONCLUSION: Our framework represents a national consensus that defines role standards for education, research and leadership services in Canadian academic divisions of general surgery. The framework can help divisions build resiliency, and enable sustained and deliberate advances in these services.


Subject(s)
Delivery of Health Care , Leadership , Canada , Consensus , Delphi Technique , Humans
18.
Glob Chang Biol ; 28(7): 2442-2460, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35023229

ABSTRACT

Robust ecological forecasting of tree growth under future climate conditions is critical to anticipate future forest carbon storage and flux. Here, we apply three ingredients of ecological forecasting that are key to improving forecast skill: data fusion, confronting model predictions with new data, and partitioning forecast uncertainty. Specifically, we present the first fusion of tree-ring and forest inventory data within a Bayesian state-space model at a multi-site, regional scale, focusing on Pinus ponderosa var. brachyptera in the southwestern US. Leveraging the complementarity of these two data sources, we parsed the ecological complexity of tree growth into the effects of climate, tree size, stand density, site quality, and their interactions, and quantified uncertainties associated with these effects. New measurements of trees, an ongoing process in forest inventories, were used to confront forecasts of tree diameter with observations, and evaluate alternative tree growth models. We forecasted tree diameter and increment in response to an ensemble of climate change projections, and separated forecast uncertainty into four different causes: initial conditions, parameters, climate drivers, and process error. We found a strong negative effect of fall-spring maximum temperature, and a positive effect of water-year precipitation on tree growth. Furthermore, tree vulnerability to climate stress increases with greater competition, with tree size, and at poor sites. Under future climate scenarios, we forecast increment declines of 22%-117%, while the combined effect of climate and size-related trends results in a 56%-91% decline. Partitioning of forecast uncertainty showed that diameter forecast uncertainty is primarily caused by parameter and initial conditions uncertainty, but increment forecast uncertainty is mostly caused by process error and climate driver uncertainty. This fusion of tree-ring and forest inventory data lays the foundation for robust ecological forecasting of aboveground biomass and carbon accounting at tree, plot, and regional scales, including iterative improvement of model skill.


Subject(s)
Forests , Pinus , Bayes Theorem , Carbon , Climate Change , Uncertainty
19.
J Gastrointest Cancer ; 53(2): 427-433, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33779898

ABSTRACT

BACKGROUND: Recent evidence from randomized trials suggests that FOLFOXIRI (fluorouracil, oxaliplatin, and irinotecan) ± bevacizumab is associated with higher response rates, with the potential for conversion of unresectable to resectable disease in metastatic colorectal cancer (mCRC). However, limited evidence is available on the efficacy and safety of this regimen in real-world patients with mCRC. The current study aims to evaluate the conversion rate and safety of FOLFOXIRI ± bevacizumab in real-world patients with unresectable mCRC. METHODS: In this retrospective multicenter population-based cohort study, patients who were diagnosed with unresectable mCRC between January 2015 and December 2018 in Saskatchewan and received FOLFOXIRI ± bevacizumab were assessed. Kaplan-Meier survival methods and the log-rank test were performed. RESULTS: A total of 28 eligible patients with a median age of 51 years (interquartile range 39-60) and a male:female ratio of 11:17 were identified; 39% had rectal cancer, 46% had extrahepatic disease, and 46% had bilobar liver metastases. Overall, 63% of the patients had a positive response to FOLFOXIRI ± bevacizumab and 53% underwent metastasectomy. Of all patients 60% had grade 3/4 toxicity and 32% required hospital admission. No treatment-related mortality was noted. After 4 years, 50% of the patients were alive. Median progression-free survival of patients who underwent surgery was 18 months (95% CI 11.3-24.7) versus 11 months (4-18.1) without surgery (p = 0.28). Median overall survival of patients with surgery was 33 months (17.5-48.5) versus 16 months (8.3-23.7) without surgery (p = 0.03). CONCLUSION: The current study suggests that FOLFOXIRI ± bevacizumab therapy in real-world patients with mCRC is associated with a high rate of conversion from unresectable to resectable metastatic disease. Patients with metastasectomy had better survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Colorectal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Cohort Studies , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Male , Middle Aged , Organoplatinum Compounds/therapeutic use , Saskatchewan
20.
Pancreas ; 51(8): 976-984, 2022 09 01.
Article in English | MEDLINE | ID: mdl-36607943

ABSTRACT

OBJECTIVES: Irreversible electroporation (IRE) is an ablation technology that uses electrical energy delivered between electrodes. If the electrodes are placed atraumatically, there is little to no risk of collateral injury, making IRE appealing for the treatment of pancreatic tumors. METHODS: We report on 20 patients with pancreatic adenocarcinoma (PAC) who underwent 21 IRE in our center. There were 6 IRE for stage 2 PAC, 11 for stage 3 PAC, 1 for stage 4 PAC, and 2 patients treated with IRE for recurrence after pancreaticoduodenectomy. One patient had local progression 18 months after IRE and received a second IRE treatment. Using propensity score matching (age, sex, stage, tumor size, and chemotherapy), cases were matched 2 to 1 with patients from the Surveillance, Epidemiology, and End Results database. RESULTS: A total of 7 cases experienced 8 complications; 4 complications were mild, and 4 were severe. Significant survival benefit was seen for patients with stage 3 PAC (27.5 vs 14.6 months for the matched group, P = 0.003); for stage 2, median survival was 15 months, and the single stage 4 patient survived 9 months after IRE treatment. CONCLUSIONS: Pancreatic cancers were safely and effectively treated with image-guided IRE in our medium-sized center.


Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/surgery , Adenocarcinoma/surgery , Electroporation/methods , Pancreatectomy , Treatment Outcome , Pancreatic Neoplasms
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