Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42-0.93 [ p <0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22-0.74 [ p <0.05]). There were no differences in the 1-, 3, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p =0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56-1.68 [ p >0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

Nowcasting the 2022 mpox outbreak in England.

In May 2022, a cluster of mpox cases were detected in the UK that could not be traced to recent travel history from an endemic region. Over the coming months, the outbreak grew, with over 3000 total cases reported in the UK, and similar outbreaks occurring worldwide. These outbreaks appeared linked to sexual contact networks between gay, bisexual and other men who have sex with men. Following the COVID-19 pandemic, local health systems were strained, and therefore effective surveillance for mpox was essential for managing public health policy. However, the mpox outbreak in the UK was characterised by substantial delays in the reporting of the symptom onset date and specimen collection date for confirmed positive cases. These delays led to substantial backfilling in the epidemic curve, making it challenging to interpret the epidemic trajectory in real-time. Many nowcasting models exist to tackle this challenge in epidemiological data, but these lacked sufficient flexibility. We have developed a nowcasting model using generalised additive models that makes novel use of individual-level patient data to correct the mpox epidemic curve in England. The aim of this model is to correct for backfilling in the epidemic curve and provide real-time characteristics of the state of the epidemic, including the real-time growth rate. This model benefited from close collaboration with individuals involved in collecting and processing the data, enabling temporal changes in the reporting structure to be built into the model, which improved the robustness of the nowcasts generated. The resulting model accurately captured the true shape of the epidemic curve in real time.

Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases.

OBJECTIVES: NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. METHODS: We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. RESULTS: In adult patients, LNK1 homozygous CB significantly improved 60-day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4-0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60-day engraftment (HR 0.4; 95% CI 0.2-0.7; p = .003), as did MICA-129 methionine+ CB grafts (HR 1.7 95% CI 1.1-2.6; p = .02). CONCLUSION: CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.

Identifying employee, workplace and population characteristics associated with COVID-19 outbreaks in the workplace: a population-based study.

OBJECTIVES: To identify risk factors that contribute to outbreaks of COVID-19 in the workplace and quantify their effect on outbreak risk. METHODS: We identified outbreaks of COVID-19 cases in the workplace and investigated the characteristics of the individuals, the workplaces, the areas they work and the mode of commute to work, through data linkages based on Middle Layer Super Output Areas in England between 20 June 2021 and 20 February 2022. We estimated population-level associations between potential risk factors and workplace outbreaks, adjusting for plausible confounders identified using a directed acyclic graph. RESULTS: For most industries, increased physical proximity in the workplace was associated with increased risk of COVID-19 outbreaks, while increased vaccination was associated with reduced risk. Employee demographic risk factors varied across industry, but for the majority of industries, a higher proportion of black/African/Caribbean ethnicities and living in deprived areas, was associated with increased outbreak risk. A higher proportion of employees in the 60-64 age group was associated with reduced outbreak risk. There were significant associations between gender, work commute modes and staff contract type with outbreak risk, but these were highly variable across industries. CONCLUSIONS: This study has used novel national data linkages to identify potential risk factors of workplace COVID-19 outbreaks, including possible protective effects of vaccination and increased physical distance at work. The same methodological approach can be applied to wider occupational and environmental health research.

Bat Motion can be Described by Leap Frogging.

We present models of bat motion derived from radio-tracking data collected over 14 nights. The data presents an initial dispersal period and a return to roost period. Although a simple diffusion model fits the initial dispersal motion we show that simple convection cannot provide a description of the bats returning to their roost. By extending our model to include non-autonomous parameters, or a leap frogging form of motion, where bats on the exterior move back first, we find we are able to accurately capture the bat's motion. We discuss ways of distinguishing between the two movement descriptions and, finally, consider how the different motion descriptions would impact a bat's hunting strategy.

Plant protein-based fibers: Fabrication, characterization, and potential food applications.

Proteins from plants have been considered as safer, healthier, and more sustainable resources than their animal counterparts. However, incomplete amino acid composition and relatively poor functionality limit their applications in foods. Structuring plant proteins to fibrous architectures enhances their physicochemical properties, which can favor various food applications. This review primarily focuses on fabrication of fibers from plant proteins via self-assembly, electrospinning, solution blow spinning, wet spinning, and high-temperature shear, as well as on several applications where such fibrous proteins assemble in quality foods. The changes of protein structure and protein-protein interactions during fiber production are discussed in detail, along with the effects of fabrication conditions and protein sources on the morphology and function of the fibers. Self-assembly requires proteolysis and subsequent peptide aggregation under specific conditions, which can be influenced by pH, salt and protein type. The spinning strategy is more scalable and produces uniformed fibers with larger length scales suitable for encapsulation, food packaging and sensor substrates. Significant progress has been made on high-temperature shear (including extrusion)-induced fibers responsible for desirable texture in meat analogues. Structuring plant proteins adds values for broadened food applications, but it remains challenging to keep processes cost-effective and environmentally friendly using food grade solvents.

Reference values for wrist-worn accelerometer physical activity metrics in England children and adolescents.

BACKGROUND: Over the last decade use of raw acceleration metrics to assess physical activity has increased. Metrics such as Euclidean Norm Minus One (ENMO), and Mean Amplitude Deviation (MAD) can be used to generate metrics which describe physical activity volume (average acceleration), intensity distribution (intensity gradient), and intensity of the most active periods (MX metrics) of the day. Presently, relatively little comparative data for these metrics exists in youth. To address this need, this study presents age- and sex-specific reference percentile values in England youth and compares physical activity volume and intensity profiles by age and sex. METHODS: Wrist-worn accelerometer data from 10 studies involving youth aged 5 to 15 y were pooled. Weekday and weekend waking hours were first calculated for youth in school Years (Y) 1&2, Y4&5, Y6&7, and Y8&9 to determine waking hours durations by age-groups and day types. A valid waking hours day was defined as accelerometer wear for ≥ 600 min·d-1 and participants with ≥ 3 valid weekdays and ≥ 1 valid weekend day were included. Mean ENMO- and MAD-generated average acceleration, intensity gradient, and MX metrics were calculated and summarised as weighted week averages. Sex-specific smoothed percentile curves were generated for each metric using Generalized Additive Models for Location Scale and Shape. Linear mixed models examined age and sex differences. RESULTS: The analytical sample included 1250 participants. Physical activity peaked between ages 6.5-10.5 y, depending on metric. For all metrics the highest activity levels occurred in less active participants (3rd-50th percentile) and girls, 0.5 to 1.5 y earlier than more active peers, and boys, respectively. Irrespective of metric, boys were more active than girls (p < .001) and physical activity was lowest in the Y8&9 group, particularly when compared to the Y1&2 group (p < .001). CONCLUSIONS: Percentile reference values for average acceleration, intensity gradient, and MX metrics have utility in describing age- and sex-specific values for physical activity volume and intensity in youth. There is a need to generate nationally-representative wrist-acceleration population-referenced norms for these metrics to further facilitate health-related physical activity research and promotion.

ADME and DMPK considerations for the discovery and development of antibody drug conjugates (ADCs).

 The therapeutic concept of antibody drug conjugates (ADCs) is to selectively target tumour cells with small molecule cytotoxic drugs to maximise cell kill benefit and minimise healthy tissue toxicity.An ADC generally consists of an antibody that targets a protein on the surface of tumour cells chemically linked to a warhead small molecule cytotoxic drug.To deliver the warhead to the tumour cell, the antibody must bind to the target protein and in general be internalised into the cell. Following internalisation, the cytotoxic agent can be released in the endosomal or lysosomal compartment (via different mechanisms). Diffusion or transport out of the endosome or lysosome allows the cytotoxic drug to express its cell-killing pharmacology. Alternatively, some ADCs (e.g. EDB-ADCs) rely on extracellular cleavage releasing membrane permeable warheads.One potentially important aspect of the ADC mechanism is the 'bystander effect' whereby the cytotoxic drug released in the targeted cell can diffuse out of that cell and into other (non-target expressing) tumour cells to exert its cytotoxic effect. This is important as solid tumours tend to be heterogeneous and not all cells in a tumour will express the targeted protein.The combination of large and small molecule aspects in an ADC poses significant challenges to the disposition scientist in describing the ADME properties of the entire molecule.This article will review the ADC landscape and the ADME properties of successful ADCs, with the aim of outlining best practice and providing a perspective of how the field can further facilitate the discovery and development of these important therapeutic modalities.

Data gaps and opportunities for comparative and conservation biology.

Biodiversity loss is a major challenge. Over the past century, the average rate of vertebrate extinction has been about 100-fold higher than the estimated background rate and population declines continue to increase globally. Birth and death rates determine the pace of population increase or decline, thus driving the expansion or extinction of a species. Design of species conservation policies hence depends on demographic data (e.g., for extinction risk assessments or estimation of harvesting quotas). However, an overview of the accessible data, even for better known taxa, is lacking. Here, we present the Demographic Species Knowledge Index, which classifies the available information for 32,144 (97%) of extant described mammals, birds, reptiles, and amphibians. We show that only 1.3% of the tetrapod species have comprehensive information on birth and death rates. We found no demographic measures, not even crude ones such as maximum life span or typical litter/clutch size, for 65% of threatened tetrapods. More field studies are needed; however, some progress can be made by digitalizing existing knowledge, by imputing data from related species with similar life histories, and by using information from captive populations. We show that data from zoos and aquariums in the Species360 network can significantly improve knowledge for an almost eightfold gain. Assessing the landscape of limited demographic knowledge is essential to prioritize ways to fill data gaps. Such information is urgently needed to implement management strategies to conserve at-risk taxa and to discover new unifying concepts and evolutionary relationships across thousands of tetrapod species.

Climate causes shifts in grey seal phenology by modifying age structure.

There are numerous examples of phenological shifts that are recognized both as indicators of climate change and drivers of ecosystem change. A pressing challenge is to understand the causal mechanisms by which climate affects phenology. We combined annual population census data and individual longitudinal data (1992-2018) on grey seals, Halicheorus grypus, to quantify the relationship between pupping season phenology and sea surface temperature. A temperature increase of 2°C was associated with a pupping season advance of approximately seven days at the population level. However, we found that maternal age, rather than sea temperature, accounted for changes in pupping date by individuals. Warmer years were associated with an older average age of mothers, allowing us to explain phenological observations in terms of a changing population age structure. Finally, we developed a matrix population model to test whether our observations were consistent with changes to the stable age distribution. This could not fully account for observed phenological shift, strongly suggesting transient modification of population age structure, for example owing to immigration. We demonstrate a novel mechanism for phenological shifts under climate change in long-lived, age- or stage-structured species with broad implications for dynamics and resilience, as well as population management.

Polyphenols Weaken Pea Protein Gel by Formation of Large Aggregates with Diminished Noncovalent Interactions.

Polyphenols are well-known native cross-linkers and gel strengthening agents for many animal proteins. However, their role in modifying plant protein gels remains unclear. In this study, multiple techniques were applied to unravel the influence of green tea polyphenols (GTP) on pea protein gels and the underlying mechanisms. We found that the elasticity and viscosity of pea protein gels decreased with increased GTP. The protein backbone became less rigid when GTP was present based on shortened T1ρH in relaxation solid-state NMR measurements. Electron microscopy and small-angle X-ray scattering showed that gels weakened by GTP possessed disrupted networks with the presence of large protein aggregates. Solvent extraction and molecular dynamic simulation revealed a reduction in hydrophobic interactions and hydrogen bonds among proteins in gels containing GTP. The current findings may be applicable to other plant proteins for greater control of gel structures in the presence of polyphenols, expanding their utilization in food and biomedical applications.

The myriad of complex demographic responses of terrestrial mammals to climate change and gaps of knowledge: A global analysis.

Approximately 25% of mammals are currently threatened with extinction, a risk that is amplified under climate change. Species persistence under climate change is determined by the combined effects of climatic factors on multiple demographic rates (survival, development and reproduction), and hence, population dynamics. Thus, to quantify which species and regions on Earth are most vulnerable to climate-driven extinction, a global understanding of how different demographic rates respond to climate is urgently needed. Here, we perform a systematic review of literature on demographic responses to climate, focusing on terrestrial mammals, for which extensive demographic data are available. To assess the full spectrum of responses, we synthesize information from studies that quantitatively link climate to multiple demographic rates. We find only 106 such studies, corresponding to 87 mammal species. These 87 species constitute <1% of all terrestrial mammals. Our synthesis reveals a strong mismatch between the locations of demographic studies and the regions and taxa currently recognized as most vulnerable to climate change. Surprisingly, for most mammals and regions sensitive to climate change, holistic demographic responses to climate remain unknown. At the same time, we reveal that filling this knowledge gap is critical as the effects of climate change will operate via complex demographic mechanisms: a vast majority of mammal populations display projected increases in some demographic rates but declines in others, often depending on the specific environmental context, complicating simple projections of population fates. Assessments of population viability under climate change are in critical need to gather data that account for multiple demographic responses, and coordinated actions to assess demography holistically should be prioritized for mammals and other taxa.

Bridging gaps in demographic analysis with phylogenetic imputation.

Phylogenetically informed imputation methods have rarely been applied to estimate missing values in demographic data but may be a powerful tool for reconstructing vital rates of survival, maturation, and fecundity for species of conservation concern. Imputed vital rates could be used to parameterize demographic models to explore how populations respond when vital rates are perturbed. We used standardized vital rate estimates for 50 bird species to assess the use of phylogenetic imputation to fill gaps in demographic data. We calculated imputation accuracy for vital rates of focal species excluded from the data set either singly or in combination and with and without phylogeny, body mass, and life-history trait data. We used imputed vital rates to calculate demographic metrics, including generation time, to validate the use of imputation in demographic analyses. Covariance among vital rates and other trait data provided a strong basis to guide imputation of missing vital rates in birds, even in the absence of phylogenetic information. Mean NRMSE for null and phylogenetic models differed by <0.01 except when no vital rates were available or for vital rates with high phylogenetic signal (Pagel's λ > 0.8). In these cases, including body mass and life-history trait data compensated for lack of phylogenetic information: mean normalized root mean square error (NRMSE) for null and phylogenetic models differed by <0.01 for adult survival and <0.04 for maturation rate. Estimates of demographic metrics were sensitive to the accuracy of imputed vital rates. For example, mean error in generation time doubled in response to inaccurate estimates of maturation time. Accurate demographic data and metrics, such as generation time, are needed to inform conservation planning processes, for example through International Union for Conservation of Nature Red List assessments and population viability analysis. Imputed vital rates could be useful in this context but, as for any estimated model parameters, awareness of the sensitivities of demographic model outputs to the imputed vital rates is essential.

Cerrando Brechas en los Análisis Demográficos con Imputación Filogenética Resumen Los métodos de imputación guiados filogenéticamente se han aplicado con poca frecuencia para estimar los valores faltantes en los datos demográficos, aunque pueden ser una herramienta poderosa para la reconstrucción de tasas vitales de supervivencia, maduración y fecundidad de especies de importancia para la conservación. Las tasas vitales imputadas podrían usarse para generar parámetros en los modelos demográficos para explorar cómo responden las poblaciones cuando se perturban las tasas vitales. Utilizamos estimaciones de tasas vitales estandarizadas para 50 especies de aves para analizar el uso de la imputación filogenética para llenar los vacíos en los datos demográficos. Calculamos la certeza de imputación para las tasas vitales de las especies focales excluidas del conjunto de datos por sí solas o en combinación y con y sin datos de filogenia, masa corporal y características de historia de vida. Usamos las tasas vitales imputadas para calcular las medidas demográficas, incluyendo el tiempo de generación, y así validar el uso de la imputación en los análisis demográficos. La covarianza entre las tasas vitales y otros datos de características proporcionó una base sólida para orientar la imputación de tasas vitales faltantes en las aves, incluso la ausencia de información filogenética. El NRMSE medio para los modelos nulo y filogenético difirió por <0.01 salvo cuando no hubo tasas vitales disponibles o para tasas vitales con una señal filogenética alta (λ de Pagel > 0.8). En estos casos, la inclusión de la masa corporal y las características de historia de vida compensó la falta de información filogenética: el error cuadrático medio de la raíz normalizada media (NRMSE) para los modelos nulo y filogenéticos difirió por <0.01 para la supervivencia adulta y <0.04 para la tasa de maduración. Las estimaciones de las medidas demográficas fueron sensibles a la certeza de las tasas vitales imputadas. Por ejemplo, el error medio en el tiempo generacional se duplicó en respuesta a las estimaciones imprecisas del tiempo de maduración. Las medidas y datos demográficos certeros, como el tiempo generacional, son necesarios para orientar los procesos de planeación de la conservación; por ejemplo, a través de las valoraciones de la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza y los análisis de viabilidad poblacional. Las tasas vitales imputadas podrían ser útiles en este contexto, pero como para cualquier tipo de parámetro de modelo estimado, el conocimiento de las sensibilidades del rendimiento del modelo demográfico es esencial para las tasas vitales imputadas.

Tumor Necrosis Factor-α-Mediated Metaplastic Inhibition of LTP Is Constitutively Engaged in an Alzheimer's Disease Model.

LTP, a fundamental mechanism of learning and memory, is a highly regulated process. One form of regulation is metaplasticity (i.e., the activity-dependent and long-lasting changes in neuronal state that orchestrate the direction, magnitude, and persistence of future synaptic plasticity). We have previously described a heterodendritic metaplasticity effect, whereby strong high-frequency priming stimulation in stratum oriens inhibits subsequent LTP in the stratum radiatum of hippocampal area CA1, potentially by engagement of the enmeshed astrocytic network. This effect may occur due to neuron-glia interactions in response to priming stimulation that leads to the release of gliotransmitters. Here we found in male rats that TNFα and associated signal transduction enzymes, but not interleukin-1ß (IL-1ß), were responsible for mediating the metaplasticity effect. Replacing priming stimulation with TNFα incubation reproduced these effects. As TNFα levels are elevated in Alzheimer's disease, we examined whether heterodendritic metaplasticity is dysregulated in a transgenic mouse model of the disease, either before or after amyloid plaque formation. We showed that TNFα and IL-1ß levels were significantly increased in aged but not young transgenic mice. Although control LTP was impaired in the young transgenic mice, it was not TNFα-dependent. In the older transgenic mice, however, LTP was impaired in a way that occluded further reduction by heterosynaptic metaplasticity, whereas LTP was entirely rescued by incubation with a TNFα antibody, but not an IL-1ß antibody. Thus, TNFα mediates a heterodendritic metaplasticity in healthy rodents that becomes constitutively and selectively engaged in a mouse model of Alzheimer's disease.SIGNIFICANCE STATEMENT The proinflammatory cytokine TNFα is known to be capable of inhibiting LTP and is upregulated several-fold in brain tissue, serum, and CSF of Alzheimer's disease (AD) patients. However, the mechanistic roles played by TNFα in plasticity and AD remain poorly understood. Here we show that TNFα and its downstream signaling molecules p38 MAPK, ERK, and JNK contribute fundamentally to a long-range metaplastic inhibition of LTP in rats. Moreover, the impaired LTP in aged APP/PS1 mice is rescued by incubation with a TNFα antibody. Thus, there is an endogenous engagement of the metaplasticity mechanism in this mouse model of AD, supporting the idea that blocking TNFα might be of therapeutic benefit in the disease.

Psychiatry and the global drugs debate: what every psychiatrist needs to know.

There are few topics that divide public opinion as sharply as the use of psychoactive substances and it is easy to see why. Substance use is complex and can be examined from numerous perspectives, including legal, health, economic, cultural and ethical. These varying approaches can lead to a range of different conclusions. Here we explore some of the common approaches adopted towards drug policy and suggest a number of principles, which may inform a psychiatrist's own view.

Electrospinning Induced Orientation of Protein Fibrils.

Amyloid-like fibrils are prepared from protein in the lab by controlled heat treatments, yet these must be further assembled to match the desirable mechanical and structural properties of biological fibers. Here, ß-lactoglobulin fibrils were incorporated into poly(ethylene oxide) fibers of 40-180 nm diameter by electrospinning. Protein fibrils presented as short segments dispersed within electrospun fibers, with no change in fibril diameter after electrospinning. Imaging analysis revealed fibrils were aligned within 20° relative to the fiber long axis, and alignment was further confirmed by polarized FTIR and anisotropic SAXS/WAXS scattering patterns. The elastic modulus of fibers increased with protein fibril content from 0.8 to 2 GPa, which is superior to reported values of silk, collagen, and gelatin. The present setup allows for manufacture of large quantities of polymeric fibers containing protein fibrils with varied diameter and mechanical strength, endowing great potential for a variety of applications.

Diversity of ageing across the tree of life.

Evolution drives, and is driven by, demography. A genotype moulds its phenotype's age patterns of mortality and fertility in an environment; these two patterns in turn determine the genotype's fitness in that environment. Hence, to understand the evolution of ageing, age patterns of mortality and reproduction need to be compared for species across the tree of life. However, few studies have done so and only for a limited range of taxa. Here we contrast standardized patterns over age for 11 mammals, 12 other vertebrates, 10 invertebrates, 12 vascular plants and a green alga. Although it has been predicted that evolution should inevitably lead to increasing mortality and declining fertility with age after maturity, there is great variation among these species, including increasing, constant, decreasing, humped and bowed trajectories for both long- and short-lived species. This diversity challenges theoreticians to develop broader perspectives on the evolution of ageing and empiricists to study the demography of more species.

Predicting the knowledge-recklessness distinction in the human brain.

Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing, rather than reckless, even when instructed on the relevant legal criteria. We used a machine-learning technique on brain imaging data to predict, with high accuracy, which mental state our participants were in. This predictive ability depended on both the magnitude of the risks and the amount of information about those risks possessed by the participants. Our results provide neural evidence of a detectable difference in the mental state of knowledge in contrast to recklessness and suggest, as a proof of principle, the possibility of inferring from brain data in which legally relevant category a person belongs. Some potential legal implications of this result are discussed.

The diversity of population responses to environmental change.

The current extinction and climate change crises pressure us to predict population dynamics with ever-greater accuracy. Although predictions rest on the well-advanced theory of age-structured populations, two key issues remain poorly explored. Specifically, how the age-dependency in demographic rates and the year-to-year interactions between survival and fecundity affect stochastic population growth rates. We use inference, simulations and mathematical derivations to explore how environmental perturbations determine population growth rates for populations with different age-specific demographic rates and when ages are reduced to stages. We find that stage- vs. age-based models can produce markedly divergent stochastic population growth rates. The differences are most pronounced when there are survival-fecundity-trade-offs, which reduce the variance in the population growth rate. Finally, the expected value and variance of the stochastic growth rates of populations with different age-specific demographic rates can diverge to the extent that, while some populations may thrive, others will inevitably go extinct.

Fast-slow continuum and reproductive strategies structure plant life-history variation worldwide.

The identification of patterns in life-history strategies across the tree of life is essential to our prediction of population persistence, extinction, and diversification. Plants exhibit a wide range of patterns of longevity, growth, and reproduction, but the general determinants of this enormous variation in life history are poorly understood. We use demographic data from 418 plant species in the wild, from annual herbs to supercentennial trees, to examine how growth form, habitat, and phylogenetic relationships structure plant life histories and to develop a framework to predict population performance. We show that 55% of the variation in plant life-history strategies is adequately characterized using two independent axes: the fast-slow continuum, including fast-growing, short-lived plant species at one end and slow-growing, long-lived species at the other, and a reproductive strategy axis, with highly reproductive, iteroparous species at one extreme and poorly reproductive, semelparous plants with frequent shrinkage at the other. Our findings remain consistent across major habitats and are minimally affected by plant growth form and phylogenetic ancestry, suggesting that the relative independence of the fast-slow and reproduction strategy axes is general in the plant kingdom. Our findings have similarities with how life-history strategies are structured in mammals, birds, and reptiles. The position of plant species populations in the 2D space produced by both axes predicts their rate of recovery from disturbances and population growth rate. This life-history framework may complement trait-based frameworks on leaf and wood economics; together these frameworks may allow prediction of responses of plants to anthropogenic disturbances and changing environments.