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1.
Proc Natl Acad Sci U S A ; 121(1): e2307984120, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38109563

RESUMO

Many studies anticipate that carbon capture and sequestration (CCS) will be essential to decarbonizing the U.S. economy. However, prior work has not estimated the time required to develop, approve, and implement a geologic sequestration site in the United States. We generate such an estimate by identifying six clearance points that must be passed before a sequestration site can become operational. For each clearance point (CP), we elicit expert judgments of the time required in the form of probability distributions and then use stochastic simulation to combine and sum the results. We find that, on average, there is a 90% chance that the time required lies between 5.5 and 9.6 y, with an upper bound of 12 y. Even using the most optimistic expert judgements, the lower bound on time is 2.7 y, and the upper bound is 8.3 y. Using the most pessimistic judgements, the lower bound is 3.5 y and the upper bound is 19.2 y. These estimates suggest that strategies must be found to safely accelerate the process. We conclude the paper by discussing seven potential strategies.

2.
Proc Natl Acad Sci U S A ; 120(7): e2219599120, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36749732

RESUMO

How do people compare the effectiveness of different social-distancing behaviors in avoiding the spread of viral infection? During the COVID pandemic, we showed 676 online respondents in the United States, United Kingdom, and Israel 30 pairs of brief videos of acquaintances meeting. We asked respondents to indicate which video from each pair depicted greater risk of COVID infection. Their choices imply that on average, respondents considered talking 14 min longer to be as risky as standing 1 foot closer, being indoors as standing 3 feet closer, being exposed to coughs or sneezes as 3 to 4 ft closer, greeting with a hug as 7 ft closer, and with a handshake as 5 ft closer. Respondents considered properly masking as protecting the wearer and interlocutor equally, removing the mask entirely or only when talking as standing 4 to 5 ft closer but wearing it under the nose as only 1 to 2 ft closer. We provide weaker evidence on beliefs about the interaction effects of different behaviors. In a more limited, ex post analysis, we find little evidence of differences in beliefs across subpopulations.


Assuntos
COVID-19 , Viroses , Humanos , Estados Unidos , COVID-19/epidemiologia , SARS-CoV-2 , Inquéritos e Questionários , Pandemias
3.
BMC Plant Biol ; 24(1): 225, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539110

RESUMO

BACKGROUND: Plants are considered the primary source of many principal bioactive compounds that have been utilized in a wide range of applications including the pharmaceutical and biotechnological industries. Therefore, there is an imperative need to modulate the production of natural bioactive components. The present study aimed to determine the importance of dried and pulverized date palm seeds (DPS) as a natural elicitor for the synthesis of secondary metabolites in Lotus arabicus L. RESULTS: The presence of various antioxidant compounds, simple sugars, amino acids, fatty acids and reasonable mineral contents was distinct in the phytochemical characterization of DPS. The major components detected in DPS analysis were the 5-(hydroxymethyl) furfural and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone. The induced callus of L. arabicus (seven weeks old) was supplemented with DPS at different concentrations (0, 2, 4, 8 and 10 g/l) in culture media. Treatment with 8 g/l DPS induced the highest antioxidant capacity, ascorbic acid content and secondary metabolites (total phenolics and flavonoids) in the produced callus. Stress biomarkers (hydrogen peroxide and malondialdehyde) were found in the control ranges except at 10 g/l DPS. The expression patterns of key genes involoved in secondary metabolism modulation, such as phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavonol synthase (FLS) and deoxyxylulose phosphate reductoisomerase (DXR), were triggered after DPS treatments. Moreover, the quantitative profiling of phenolic and flavonoid compounds showed that supplementation with DPS, especially at 8 g/l, led to pronounced increases in most of the measured compounds. CONCLUSION: The marked upregulation of eliciting-responsive genes and overproduction of secondary metabolites provide molecular-based evidence for intensifying the principal pathways of phenylpropanoid, flavonoid and terpenoid biosynthesis. Overall, the present in vitro study highlights the stimulating capacity of DPS utilization to improve the bioactive components of L. arabicus at the physiological and molecular levels, enhancing its potential as a medicinal herb.


Assuntos
Lotus , Phoeniceae , Antioxidantes/metabolismo , Lotus/metabolismo , Phoeniceae/metabolismo , Pós , Flavonoides/metabolismo , Fenóis/metabolismo , Sementes/metabolismo
4.
BMC Plant Biol ; 24(1): 657, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987699

RESUMO

The development and production of secondary metabolites from priceless medicinal plants are restricted by drought stress. Mentha pulegium L. belongs to the Lamiaceae family and is a significant plant grown in the Mediterranean region for its medicinal and aesthetic properties. This study investigated the effects of three polyethylene glycol (PEG) (0, 5, and 10%) as a drought stress inducer and four silicon nanoparticle (SiNP) (0, 25, 50, and 100 ppm) concentrations as an elicitor to overcome the adverse effect of drought stress, on the growth parameters and bioactive chemical composition of M. pulegium L. plants grown in vitro. The experiment was performed as a factorial experiment using a completely randomized design (CRD) consisting of 12 treatments with two factors (3 PEG × 4 SiNPs concentrations), 6 replicates were used for each treatment for a total of 72 experimental units.The percentage of shoot formation was inversely proportional to the PEG concentration; for the highest PEG concentration, the lowest percentage of shoot formation (70.26%) was achieved at 10% PEG. SiNPs at 50 ppm enhanced shoot formation, the number of shoots, shoot height, fresh and dry weight, rosmarinic acid, total phenols, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. The methanol extract from M. pulegium revealed the presence of significant secondary metabolites using gas chromatography‒mass spectrometry (GC-MS). The principal constituents of the extract were limonene (2.51, 2.99%), linalool (3.84, 4.64%), geraniol (6.49, 8.77%), menthol (59.73, 65.43%), pulegone (3.76, 2.76%) and hexadecanoic acid methyl ester or methyl palmitate (3.2, 4.71%) for the 0 ppm SiNPs, PEG 0% and 50 ppm SiNPs, and PEG 10%, respectively. Most of the chemical components identified by GC‒MS in the methanol extract were greater in the 50 ppm SiNP and 10% PEG treatment groups than in the control group. SiNP improves drought tolerance by regulating biosynthesis and accumulating some osmolytes and lessens the negative effects of polyethylene glycol-induced drought stress.Based on the results, the best treatment for most of the parameters was 50 ppm SiNPs combined with 10% PEG, the morphological and chemical characteristics were inversely proportional to the PEG concentration, as the highest PEG concentration (10%) had the lowest results. Most parameters decreased at the highest SiNP concentration (100 ppm), except for the DPPH scavenging percentage, as there was no significant difference between the 50 and 100 ppm SiNPs.


Assuntos
Secas , Mentha pulegium , Nanopartículas , Silício , Mentha pulegium/química , Mentha pulegium/metabolismo , Nanopartículas/química , Silício/metabolismo , Silício/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Antioxidantes/metabolismo , Estresse Fisiológico , Monoterpenos Acíclicos/metabolismo
5.
Planta ; 259(4): 80, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436711

RESUMO

MAIN CONCLUSION: This review has explored the importance of using a synergistic approach of nano-elicitation and hydroponics to improve plant growth and metabolite production. Furthermore, it emphasizes the significance of green nanotechnology and eco-friendly practices while utilizing this approach to promote the development of a sustainable agriculture system. Nano-elicitation stimulates metabolic processes in plants using nanoparticles (NPs) as elicitors. The stimulation of these biochemical processes can enhance plant yield and productivity, along with the production of secondary metabolites. Nanoparticles have garnered the attention of scientific community because of their unique characteristics, such as incredibly small size and large surface-to-volume ratio, which make them effective elicitors. Hydroponic systems, which optimize growing conditions to increase plant production, are typically used to study the effect of elicitors. By integrating these two approaches, the qualitative and quantitative output of plants can be increased while employing minimal resources. As the global demand for high-quality crops and bioactive compounds surges, embracing this synergistic approach alongside sustainable farming practices can pave the way for resilient agricultural systems, ensuring food security and fostering an eco-friendly environment.


Assuntos
Agricultura , Produtos Agrícolas , Metabolismo Secundário , Hidroponia , Fazendas
6.
Plant Biotechnol J ; 22(1): 233-247, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37772738

RESUMO

Paclitaxel is one of the most effective anticancer drugs ever developed. Although the most sustainable approach to its production is provided by plant cell cultures, the yield is limited by bottleneck enzymes in the taxane biosynthetic pathway: baccatin-aminophenylpropanoyl-13-O-transferase (BAPT) and 3'-N-debenzoyltaxol N-benzoyltransferase (DBTNBT). With the aim of enhancing paclitaxel production by overcoming this bottleneck, we obtained distinct lines of Taxus baccata in vitro roots, each independently overexpressing either of the two flux-limiting genes, BAPT or DBTNBT, through a Rhizobium rhizogenes A4-mediated transformation. Due to the slow growth rate of the transgenic Taxus roots, they were dedifferentiated to obtain callus lines and establish cell suspensions. The transgenic cells were cultured in a two-stage system and stimulated for taxane production by a dual elicitation treatment with 1 µm coronatine plus 50 mm of randomly methylated-ß-cyclodextrins. A high overexpression of BAPT (59.72-fold higher at 48 h) and DBTNBT (61.93-fold higher at 72 h) genes was observed in the transgenic cell cultures, as well as an improved taxane production. Compared to the wild type line (71.01 mg/L), the DBTNBT line produced more than four times higher amounts of paclitaxel (310 mg/L), while the content of this taxane was almost doubled in the BAPT line (135 mg/L). A transcriptional profiling of taxane biosynthetic genes revealed that GGPPS, TXS and DBAT genes were the most reactive to DBTNBT overexpression and the dual elicitation, their expression increasing gradually and constantly. The same genes exhibited a pattern of isolated peaks of expression in the elicited BAPT-overexpressing line.


Assuntos
Paclitaxel , Taxus , Paclitaxel/metabolismo , Taxus/genética , Taxus/metabolismo , Células Cultivadas , Taxoides/farmacologia , Taxoides/metabolismo
7.
Plant Cell Environ ; 47(7): 2675-2692, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38600764

RESUMO

The restriction of plant-symbiont dinitrogen fixation by an insect semiochemical had not been previously described. Here we report on a glycosylated triketide δ-lactone from Nephrotoma cornicina crane flies, cornicinine, that causes chlorosis in the floating-fern symbioses from the genus Azolla. Only the glycosylated trans-A form of chemically synthesized cornicinine was active: 500 nM cornicinine in the growth medium turned all cyanobacterial filaments from Nostoc azollae inside the host leaf-cavities into akinetes typically secreting CTB-bacteriocins. Cornicinine further inhibited akinete germination in Azolla sporelings, precluding re-establishment of the symbiosis during sexual reproduction. It did not impact development of the plant Arabidopsis thaliana or several free-living cyanobacteria from the genera Anabaena or Nostoc but affected the fern host without cyanobiont. Fern-host mRNA sequencing from isolated leaf cavities confirmed high NH4-assimilation and proanthocyanidin biosynthesis in this trichome-rich tissue. After cornicinine treatment, it revealed activation of Cullin-RING ubiquitin-ligase-pathways, known to mediate metabolite signaling and plant elicitation consistent with the chlorosis phenotype, and increased JA-oxidase, sulfate transport and exosome formation. The work begins to uncover molecular mechanisms of cyanobiont differentiation in a seed-free plant symbiosis important for wetland ecology or circular crop-production today, that once caused massive CO2 draw-down during the Eocene geological past.


Assuntos
Dípteros , Gleiquênias , Lactonas , Nostoc , Gleiquênias/citologia , Gleiquênias/metabolismo , Gleiquênias/microbiologia , Gleiquênias/fisiologia , Lactonas/química , Lactonas/metabolismo , Nostoc/genética , Nostoc/fisiologia , Dípteros/química , Simbiose , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Nitratos/metabolismo , RNA Bacteriano/metabolismo , Bacteriocinas/genética , Folhas de Planta/metabolismo
8.
Toxicol Appl Pharmacol ; 489: 116995, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38862081

RESUMO

Identification of Endocrine-Disrupting Chemicals (EDCs) in a regulatory context requires a high level of evidence. However, lines of evidence (e.g. human, in vivo, in vitro or in silico) are heterogeneous and incomplete for quantifying evidence of the adverse effects and mechanisms involved. To date, for the regulatory appraisal of metabolism-disrupting chemicals (MDCs), no harmonised guidance to assess the weight of evidence has been developed at the EU or international level. To explore how to develop this, we applied a formal Expert Knowledge Elicitation (EKE) approach within the European GOLIATH project. EKE captures expert judgment in a quantitative manner and provides an estimate of uncertainty of the final opinion. As a proof of principle, we selected one suspected MDC -triphenyl phosphate (TPP) - based on its related adverse endpoints (obesity/adipogenicity) relevant to metabolic disruption and a putative Molecular Initiating Event (MIE): activation of peroxisome proliferator activated receptor gamma (PPARγ). We conducted a systematic literature review and assessed the quality of the lines of evidence with two independent groups of experts within GOLIATH, with the objective of categorising the metabolic disruption properties of TPP, by applying an EKE approach. Having followed the entire process separately, both groups arrived at the same conclusion, designating TPP as a "suspected MDC" with an overall quantitative agreement exceeding 85%, indicating robust reproducibility. The EKE method provides to be an important way to bring together scientists with diverse expertise and is recommended for future work in this area.


Assuntos
Disruptores Endócrinos , Organofosfatos , Animais , Humanos , Disruptores Endócrinos/toxicidade , Prova Pericial , Organofosfatos/toxicidade , PPAR gama/metabolismo , PPAR gama/agonistas , Medição de Risco
9.
Cerebellum ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713312

RESUMO

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1-2 years, 1-2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.

10.
Stat Med ; 43(19): 3595-3612, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38881219

RESUMO

An assurance calculation is a Bayesian alternative to a power calculation. One may be performed to aid the planning of a clinical trial, specifically setting the sample size or to support decisions about whether or not to perform a study. Immuno-oncology is a rapidly evolving area in the development of anticancer drugs. A common phenomenon that arises in trials of such drugs is one of delayed treatment effects, that is, there is a delay in the separation of the survival curves. To calculate assurance for a trial in which a delayed treatment effect is likely to be present, uncertainty about key parameters needs to be considered. If uncertainty is not considered, the number of patients recruited may not be enough to ensure we have adequate statistical power to detect a clinically relevant treatment effect and the risk of an unsuccessful trial is increased. We present a new elicitation technique for when a delayed treatment effect is likely and show how to compute assurance using these elicited prior distributions. We provide an example to illustrate how this can be used in practice and develop open-source software to implement our methods. Our methodology has the potential to improve the success rate and efficiency of Phase III trials in immuno-oncology and for other treatments where a delayed treatment effect is expected to occur.


Assuntos
Teorema de Bayes , Projetos de Pesquisa , Humanos , Tamanho da Amostra , Modelos Estatísticos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Ensaios Clínicos Fase III como Assunto/métodos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Ensaios Clínicos como Assunto/métodos , Simulação por Computador , Antineoplásicos/uso terapêutico , Fatores de Tempo , Análise de Sobrevida , Atraso no Tratamento
11.
Value Health ; 27(6): 737-745, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38428813

RESUMO

OBJECTIVES: Multiple methods are available for collecting health preference information. However, information on the design and analysis of novel methods is limited. This article aims to provide the first introduction into the design and analysis of multidimensional thresholding (MDT). METHODS: We introduce MDT as a 2-step approach: First, participants rank the largest possible improvements in all considered attributes by their importance. Second, participants complete a series of systematically combined trade-off questions. Hit-and-Run sampling is used for obtaining preference weights. We also use a computational experiment to compare different MDT designs. RESULTS: The outlined MDT can generate preference information suitable for specifying a multiattribute utility function at the individual level. The computational experiment demonstrates the method's ability to recover preference weights at a high level of precision. While all designs in the computation experiment perform comparably well on average, the design outlined in the paper stands out with a high level of precision even if differences in relative attribute importance are large. CONCLUSION: MDT is suitable for preference elicitation, in particular if sample sizes are small. Future research should help improve the methods (e.g., remove the need for an initial ranking) to increase the potential reach of MDT.


Assuntos
Preferência do Paciente , Humanos , Feminino , Masculino , Adulto , Projetos de Pesquisa , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos e Questionários , Comportamento de Escolha
12.
Value Health ; 27(1): 15-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37820753

RESUMO

OBJECTIVES: Limitations in conventional cost-effectiveness methods have led to calls for incorporation of additional value elements in assessments of health technologies. However, gaps remain in how additional value elements may inform decision making. This study aimed to prioritize additional value elements from the perspective of healthy individuals without a specific condition or indicated for a specific treatment in the United States among a multistakeholder panel and compare the importance of perspective-specific value elements. METHODS: Additional value elements were prioritized in 2 phases: (1) we identified and categorized additional value elements in a targeted literature review, and (2) we convened a multistakeholder group-based preference elicitation study (N = 28) to evaluate the description of each value element and rank and generate normalized weights of each value element for its significance in value assessment. The importance of additional value elements was also weighted relative to patient-centric value elements. RESULTS: The rank and weight of contextual value elements among 28 stakeholders were "severity of the disease" (26.2%), "disadvantaged and vulnerable target populations highly represented" (21.8%), "broader economic impact" (17.3%), "risk protection" (13.8%), "rarity of the disease" (11.3%), and "novel mechanism of action" (9.7%). Relative weight of the additional value elements versus patient-centric value elements was 52% and 48%, respectively. CONCLUSIONS: Study findings may inform priority setting for value frameworks and emerging US government assessments. The group-based elicitation method is repeatable and useful for structured deliberative processes in value assessment and may help improve the consistency and predictability of what is important to stakeholders.


Assuntos
Avaliação de Processos e Resultados em Cuidados de Saúde , Assistência Centrada no Paciente , Humanos , Estados Unidos , Participação dos Interessados
13.
Value Health ; 27(3): 376-382, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38154596

RESUMO

OBJECTIVES: Traditional preference elicitation methods, such as discrete choice experiments or time trade-off, usually require large sample sizes. This can limit their applicability in patient populations, where recruiting enough participants can be challenging. The objective of this study was to test a new method, called the Online elicitation of Personal Utility Functions (OPUF) approach, to derive an EQ-5D-5L value set from a relatively small sample of patients with rheumatic diseases. METHODS: OPUF is a new type of online survey that implements compositional preference elicitation techniques. Central to the method are 3 valuation steps: (1) dimension weighting, (2) level rating, and (3) anchoring. An English demo version of the OPUF survey can be accessed at https://valorem.health/eq5d5l. From the responses, a personal EQ-5D-5L utility function can be constructed for each participant, and a group-level value set can be derived by aggregating model coefficients across participants. RESULTS: A total of 122 patients with rheumatic disease from Germany completed the OPUF survey. The survey was generally well received; most participants completed the survey in less than 20 minutes and were able to derive a full EQ-5D-5L value set. The precision of mean coefficients was high, despite the small sample size. CONCLUSIONS: Our findings demonstrate that OPUF can be used to derive an EQ-5D-5L value set from a relatively small sample of patients. Although the method is still under development, we think that it has the potential to be a valuable preference elicitation tool and to complement traditional methods in several areas.


Assuntos
Nível de Saúde , Doenças Reumáticas , Humanos , Qualidade de Vida , Inquéritos e Questionários , Alemanha
14.
Value Health ; 27(5): 642-654, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369283

RESUMO

OBJECTIVES: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD) and valued to generate United Kingdom and German preference weights. METHODS: A PWM consists of a classification system to describe health and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the United Kingdom and German public. Responses were modeled to generate utility values for all possible health states. RESULTS: The classification system has 5 items across the 3 domains of VILL-33: reading and accessing information, mobility and safety, and emotional well-being. The DCE samples (United Kingdom: n = 1004, Germany: n = 1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients. CONCLUSIONS: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both United Kingdom and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD in which generic preference-weighted measures typically lack sensitivity.


Assuntos
Degeneração Macular , Preferência do Paciente , Psicometria , Humanos , Degeneração Macular/psicologia , Degeneração Macular/fisiopatologia , Feminino , Masculino , Idoso , Inquéritos e Questionários , Alemanha , Reino Unido , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Qualidade de Vida
15.
BMC Med Res Methodol ; 24(1): 128, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834992

RESUMO

BACKGROUND: Clinical prediction models can help identify high-risk patients and facilitate timely interventions. However, developing such models for rare diseases presents challenges due to the scarcity of affected patients for developing and calibrating models. Methods that pool information from multiple sources can help with these challenges. METHODS: We compared three approaches for developing clinical prediction models for population screening based on an example of discriminating a rare form of diabetes (Maturity-Onset Diabetes of the Young - MODY) in insulin-treated patients from the more common Type 1 diabetes (T1D). Two datasets were used: a case-control dataset (278 T1D, 177 MODY) and a population-representative dataset (1418 patients, 96 MODY tested with biomarker testing, 7 MODY positive). To build a population-level prediction model, we compared three methods for recalibrating models developed in case-control data. These were prevalence adjustment ("offset"), shrinkage recalibration in the population-level dataset ("recalibration"), and a refitting of the model to the population-level dataset ("re-estimation"). We then developed a Bayesian hierarchical mixture model combining shrinkage recalibration with additional informative biomarker information only available in the population-representative dataset. We developed a method for dealing with missing biomarker and outcome information using prior information from the literature and other data sources to ensure the clinical validity of predictions for certain biomarker combinations. RESULTS: The offset, re-estimation, and recalibration methods showed good calibration in the population-representative dataset. The offset and recalibration methods displayed the lowest predictive uncertainty due to borrowing information from the fitted case-control model. We demonstrate the potential of a mixture model for incorporating informative biomarkers, which significantly enhanced the model's predictive accuracy, reduced uncertainty, and showed higher stability in all ranges of predictive outcome probabilities. CONCLUSION: We have compared several approaches that could be used to develop prediction models for rare diseases. Our findings highlight the recalibration mixture model as the optimal strategy if a population-level dataset is available. This approach offers the flexibility to incorporate additional predictors and informed prior probabilities, contributing to enhanced prediction accuracy for rare diseases. It also allows predictions without these additional tests, providing additional information on whether a patient should undergo further biomarker testing before genetic testing.


Assuntos
Teorema de Bayes , Diabetes Mellitus Tipo 2 , Doenças Raras , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Doenças Raras/diagnóstico , Estudos de Casos e Controles , Feminino , Diabetes Mellitus Tipo 1/diagnóstico , Masculino , Biomarcadores/análise , Adolescente , Adulto , Criança
16.
Conserv Biol ; : e14372, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39268844

RESUMO

Communities have a strong role in protecting biodiversity. In addition to participation in restoration, a range of actions in the public or private sphere may support biodiversity. Despite this, there is a lack of clarity about what actions should be prioritized for behavior change campaigns. We developed and applied a method to prioritize community actions for biodiversity conservation that incorporates an expert-based assessment of impact and a community-informed measure of the likelihood of uptake. In stage 1, experts (n = 143) completed a survey that quantified the relative impact of actions based on best-worst scaling of perceived impact. In stage 2, surveyed community members (n = 3200) ranked the likelihood of adopting actions based on the ease or difficulty of performing each action, and the opportunity for change based on the proportion of respondents not yet engaging in each behavior. Experts gave the following actions the highest ranking for impact: voting for the environment (first), participating in restoration in ecological priority areas (second), and purchasing and protecting remnant bushland (third). When considering the disciplinary background and institutional background of experts, voting and participating in restoration activities remained in the upper ranked options. However, there was some divergence between these groups. For example, reducing beef consumption was ranked third by university-based experts but ranked 28th by experts based in state government. Overall, community members ranked the following behaviors as most likely to be adopted: following quarantine laws (first), reducing plastic use (second), and managing pets (third). Top likelihood ranking of actions was minimally affected by community characteristics (nature relatedness, gender, location). Integrating these findings, the action ranked most favorably for impact, likelihood, and opportunity was participating in restoration. Choosing actions for behavior change campaigns requires consideration of the entire social-ecological system-from social factors that enable or constrain adoption to the ecological impact of actions across relevant social and ecological contexts.


Inducción de perspectivas diversas para priorizar las acciones comunitarias a favor de la conservación de la biodiversidad Las comunidades juegan un papel importante en la protección de la biodiversidad. Además de participar en la restauración, existe una gama de acciones públicas y privadas que pueden ayudar a la biodiversidad. A pesar de esto, no está claro cuáles acciones deben priorizarse en las campañas de cambio conductual. Desarrollamos y aplicamos un método para priorizar las acciones comunitarias a favor de la conservación de la biodiversidad que incorpora la evaluación por experto del impacto y la medida comunitaria de la probabilidad de captación. En la fase 1, los expertos (n = 143) completaron una encuesta que cuantificó el impacto relativo de las acciones con base en una escala mejor­peor del impacto percibido. En la fase 2, los miembros de la comunidad (n = 3200) clasificaron la probabilidad del éxito de las acciones con base en la proporción de respondientes que todavía no participan en cada comportamiento. Los expertos otorgaron la clasificación más alta para el impacto a las siguientes acciones: votar por el ambiente (primero), participar en la restauración de áreas ecológicas prioritarias (segundo) y adquirir y proteger matorrales remanentes (tercero). Cuando consideramos la formación disciplinaria e institucional de los expertos, la votación y la participación en las actividades de restauración permanecieron en las opciones con clasificación más alta; sin embargo, existió una divergencia entre estos grupos. Por ejemplo, los expertos de las universidades clasificaron en tercero la reducción del consumo de carne de res, pero los expertos del gobierno estatal lo clasificaron en vigésimo octavo. En general, los miembros de la comunidad clasificaron los siguientes comportamientos como los más probables de ser adoptados: seguir las normas de cuarentena (primero), reducir el uso de plásticos (segundo) y el manejo de mascotas (tercero). Las características comunitarias (relación con la naturaleza, género, ubicación) afectaron en lo mínimo a la clasificación más alta de probabilidad de las acciones. Al integrar estos resultados, la acción mejor clasificada en cuanto a impacto, probabilidad y oportunidad fue la participación en la restauración. La selección de acciones para las campañas de cambio conductual requiere que se considere todo el sistema socio ecológico ­ desde los factores sociales que permiten o restringen la conservación hasta las acciones de impacto ecológico relevantes en los contextos sociales y ecológicos.

17.
Conserv Biol ; : e14370, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225270

RESUMO

Expert judgment underpins assessment of threatened ecosystems. However, experts are often narrowly defined, and variability in their judgments may be substantial. Models built from structured elicitation with large diverse expert panels can contribute to more consistent and transparent decision-making. We conducted a structured elicitation under a broad definition of expertise to examine variation in judgments of ecosystem viability and collapse in a critically endangered ecosystem. We explored whether variation in judgments among 83 experts was related to affiliation and management expertise and assessed performance of an average model based on common ecosystem indicators. There were systematic differences among individuals, much of which were not explained by affiliation or expertise. However, of the individuals affiliated with government, those in conservation and environmental departments were more likely to determine a patch was viable than those in agriculture and rural land management. Classification errors from an average model, in which all individuals were weighted equally, were highest among government agriculture experts (27%) and lowest among government conservation experts (12%). Differences were mostly cases in which the average model predicted a patch was viable but the individual thought it was not. These differences arose primarily for areas that were grazed or cleared of mature trees. These areas are often the target of restoration, but they are also valuable for agriculture. These results highlight the potential for conflicting advice and disagreement about policies and actions for conserving and restoring threatened ecosystems. Although adoption of an average model can improve consistency of ecosystem assessment, it can fail to capture and convey diverse opinions held by experts. Structured elicitation and models of ecosystem viability play an important role in providing data-driven evidence of where differences arise among experts to support engagement and discussion among stakeholders and decision makers and to improve the management of threatened ecosystems.


Análisis de los modelos de opiniones de expertos para informar la evaluación de la viabilidad y el colapso ambiental Resumen La evaluación de los ecosistemas amenazados se basa en la opinión de los expertos. Sin embargo, la definición de experto suele ser limitada y la variabilidad de sus juicios puede ser considerable. Los modelos elaborados a partir de consultas estructuradas con grupos de expertos amplios y diversos pueden contribuir a una toma de decisiones más coherente y transparente. Realizamos una consulta estructurada con una definición amplia de experto para analizar la variación en los juicios sobre la viabilidad y el colapso de un ecosistema en peligro crítico. Exploramos si la variación en los juicios entre 83 expertos estaba relacionada con la afiliación y la experiencia en gestión y evaluamos el rendimiento de un modelo medio basado en indicadores comunes del ecosistema. Observamos diferencias sistemáticas entre los expertos, gran parte de las cuales no se explicaban por la afiliación o la experiencia. Sin embargo, entre los expertos vinculados a la administración pública, los de los departamentos de conservación y medio ambiente tenían más probabilidades de determinar que una parcela era viable que los de agricultura y gestión de tierras rurales. Los errores de clasificación de un modelo medio con todos los individuos ponderados por igual, fueron mayores entre los expertos gubernamentales en agricultura (27%) y menores entre los expertos gubernamentales en conservación (12%). En la mayoría de los casos, las diferencias se debían a que el modelo medio predecía que una parcela era viable, pero el individuo pensaba que no lo era. Estas diferencias surgieron sobre todo en zonas que habían sido pastoreadas o con una tala total de árboles maduros. Estas zonas suelen ser objeto de restauración, pero también son valiosas para la agricultura. Estos resultados ponen de manifiesto la posibilidad de que se produzcan consejos contradictorios y desacuerdos sobre las políticas y acciones de conservación y restauración de los ecosistemas pastoreados y forestales. Si bien la adopción de un modelo medio puede mejorar la coherencia de la evaluación de los ecosistemas, también puede fallar a la hora de captar y transmitir las diversas opiniones de los expertos. Las consultas estructuradas y los modelos de viabilidad de los ecosistemas desempeñan un papel importante a la hora de aportar pruebas basadas en datos de dónde surgen las diferencias entre los expertos para apoyar el compromiso y el debate entre las partes interesadas y los responsables de la toma de decisiones, así como para mejorar la gestión de los ecosistemas amenazados.

18.
Conserv Biol ; 38(5): e14320, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39248748

RESUMO

Illegal collecting of wild Venus flytraps (Dionaea muscipula) for the horticultural trade represents a persistent threat to populations of the species across their endemic range in the coastal plain of North and South Carolina (United States). Although wild collecting of Venus flytraps is not a novel threat, there has been very little research on the impacts of collecting on the species' conservation to date or why an illegal trade persists alongside a legal one. We drew on qualitative expert stakeholder elicitation to contextualize the threat of illegal collecting to the long-term conservation of Venus flytraps in relation to other anthropogenic threats. Expert elicitation included botanical and conservation researchers, cognizant state and federal agency staff, land managers, and conservation nonprofit actors. The workshop included mapping of supply chain structures and prioritization of social and environmental harms. Expert consensus determined illegal collecting is an ongoing problem for Venus flytrap conservation, but habitat destruction, degradation, and fire suppression are the most significant threats to flytrap conservation. Supply chain analysis showed that observable social and environmental harms of the trade are focused at the supply stage and that less is known about transit and demand stages. Key research gaps identified include a lack of understanding of plant laundering practices relevant to a range of desirable plant taxa; the role of commercial nurseries in illicit horticultural supply chains; motivations for engaging in Venus flytrap collecting; and the persistent demand for illegally harvested plants when cultivated, legally obtainable plants are readily available. Our findings and methodology are relevant to a range of ornamental plants affected by illegal trade for which robust social data on illegal collecting drivers are lacking.


Evaluación experta del impacto de la colecta ilegal de venus atrapamoscas y las prioridades de investigación sobre el mercado ilegal Resumen La colecta ilegal de venus atrapamoscas (Dionaea muscipula) silvestres para el mercado de horticultura representa una amenaza constante para las poblaciones de la especie a lo largo de su distribución endémica en la planicie costera de Carolina del Norte y del Sur, Estados Unidos. Aunque esta colecta no es una amenaza novedosa, a la fecha se ha investigado muy poco sobre su impacto en la conservación de la especie o por qué el mercado ilegal persiste a la par del legal. Partimos del conocimiento cualitativo de los actores expertos para contextualizar la amenaza de la colecta ilegal para la conservación a largo plazo de la venus atrapamoscas en relación con otras amenazas antropogénicas. Este conocimiento involucró a investigadores de la conservación y la botánica, personal consciente de agencias federales y estatales y actores de la conservación sin fines de lucro. El taller incluyó el mapeo de las estructuras de las cadenas de suministro y la priorización de los daños sociales y ambientales. El consenso de los expertos determinó que la colecta ilegal es un problema continuo para la conservación de la venus atrapamoscas, pero la destrucción y degradación del hábitat, así como la contención de incendios son las amenazas más significativas. El análisis de las cadenas de suministro mostró que los daños ambientales y sociales observables en el mercado se enfocan en la fase de suministro y que se sabe poco sobre las fases de tránsito y demanda. Los vacíos de investigación más importantes incluyen la falta de entendimiento de las prácticas de lavado de plantas relevantes para un rango de taxones deseables de plantas; el papel de los viveros comerciales en las cadenas de suministro de la horticultura ilícita; los motivos para participar en la colecta de venus atrapamoscas; y la demanda continua de plantas cosechadas ilegalmente cuando ya hay disponibilidad de plantas cultivadas que se obtienen legalmente. Nuestros descubrimientos y metodología son relevantes para una gama de plantas ornamentales afectadas por el mercado ilegal para las cuales hay carencia de datos sociales sólidos sobre los factores de colecta ilegal.


Assuntos
Comércio , Conservação dos Recursos Naturais , Droseraceae , Conservação dos Recursos Naturais/legislação & jurisprudência , Conservação dos Recursos Naturais/métodos , Droseraceae/fisiologia , South Carolina , Ecossistema
19.
Cost Eff Resour Alloc ; 22(1): 10, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291472

RESUMO

Preference elicitation is widely used within health economic evaluations to inform coverage decisions. However, coverage decisions involve questions of social justice and it is unclear what role empirical evidence about preferences can play here. This study reviews the prevalent normative frameworks for using population-based preference elicitation and the criticisms they face, and proposes an alternative based on constitutional economics. The frameworks reviewed include a supposedly value-neutral framework of preferences as predictors of choice, preference utilitarian frameworks that aim to maximize preference satisfaction, and substantive consequentialist frameworks that aim to maximize happiness, health, or capabilities. The proposed alternative implements the idea that indices of social value are tools for conflict resolution, rather than tools for maximization. Preference elicitation is used for validating values generated by multi-criteria decision analysis results within representative processes of stakeholder deliberation.

20.
J Biomed Inform ; 157: 104691, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39019302

RESUMO

BACKGROUND: Persons with cognitive impairment may experience difficulties with language and cognition that interfere with their ability to communicate about health-related decision making. OBJECTIVE: We developed a visual elicitation technique to facilitate conversations about preferences concerning potential future supportive care needs and explored the utility of this technique in a qualitative interview study. METHODS: We conducted 15 online interviews with persons with mild cognitive impairment and mild to moderate dementia, using storytelling and a virtual tool designed to facilitate discussion about preferences for supportive care. Interviews were transcribed verbatim and analyzed using an inductive qualitative data analysis method. We report our findings with respect to several main themes. First, we considered participants' perspectives on supportive care. Next, we examined the utility of the tool for engaging participants in conversation through two themes: cognitive and communicative processes exhibited by participants; and dialogic interactions between the interviewer and the participant. RESULTS: With respect to participants' perspectives on supportive care, common themes included considerations relating to informal caregivers such as availability and burden, and the quality of care options such as paid caregivers. Other themes, such as the importance of making decisions as a family, considerations related to facing these challenges on one's own, and the fluid nature of decision making, also emerged. Common communicative processes included not being responsive to the question and unclear responses. Common cognitive processes included uncertainty and introspection, or self-awareness, of one's cognitive abilities. Last, we examined dialogic interactions between the participant and the interviewer to better understand engagement with the tool. The interviewer was active in using the visualization tool to facilitate the conversation, and participants engaged with the interface to varying degrees. Some participants expressed greater agency and involvement through suggesting images, elaborating on their or the interviewer's comments, and suggesting icon labels. CONCLUSION: This article presents a visual method to engage older adults with cognitive impairment in active dialogue about complex decisions. Though designed for a research setting, the diverse communication and participant-interviewer interaction patterns observed in this study suggest that the tool might be adapted for use in clinical or community settings.


Assuntos
Disfunção Cognitiva , Comunicação , Humanos , Disfunção Cognitiva/terapia , Feminino , Masculino , Idoso , Cuidadores/psicologia , Pessoa de Meia-Idade , Tomada de Decisões , Idoso de 80 Anos ou mais , Demência/terapia
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