The response of coastal wetlands to sea-level rise during the twenty-first century remains uncertain. Global-scale projections suggest that between 20 and 90 per cent (for low and high sea-level rise ...scenarios, respectively) of the present-day coastal wetland area will be lost, which will in turn result in the loss of biodiversity and highly valued ecosystem services
. These projections do not necessarily take into account all essential geomorphological
and socio-economic system feedbacks
. Here we present an integrated global modelling approach that considers both the ability of coastal wetlands to build up vertically by sediment accretion, and the accommodation space, namely, the vertical and lateral space available for fine sediments to accumulate and be colonized by wetland vegetation. We use this approach to assess global-scale changes in coastal wetland area in response to global sea-level rise and anthropogenic coastal occupation during the twenty-first century. On the basis of our simulations, we find that, globally, rather than losses, wetland gains of up to 60 per cent of the current area are possible, if more than 37 per cent (our upper estimate for current accommodation space) of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels. In contrast to previous studies
, we project that until 2100, the loss of global coastal wetland area will range between 0 and 30 per cent, assuming no further accommodation space in addition to current levels. Our simulations suggest that the resilience of global wetlands is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and such infrastructure is expected to change over the twenty-first century. Rather than being an inevitable consequence of global sea-level rise, our findings indicate that large-scale loss of coastal wetlands might be avoidable, if sufficient additional accommodation space can be created through careful nature-based adaptation solutions to coastal management.
Tisagenlecleucel is a CD19-specific chimeric antigen receptor (CAR)-T cell therapy approved for patients aged ≤25 years with relapsed or refractory B cell precursor acute lymphoblastic leukemia ...(B-ALL) and adults with relapsed or refractory diffuse large B cell lymphoma (DLBCL). The initial tisagenlecleucel manufacturing process technology was developed at an academic center and was subsequently transferred, optimized, validated, and scaled out to supply large global trials before commercialization. Tisagenlecleucel manufactured in two centralized facilities has been successfully used in global multicenter trials for B-ALL and DLBCL (>50 clinical centers in 12 countries). In this paper, we describe some of the continuous process improvements made to tisagenlecleucel manufacturing over time to meet global demand while maintaining and improving product quality. During early tisagenlecleucel clinical trials, process enhancements were made to address logistical challenges related to manufacturing for multicenter trials and to accommodate the variability observed in patient starting cellular material. These enhancements resulted in improvements in manufacturing capacity, process robustness, manufacturing success rates, and product quality, and reductions in throughput time. In summary, through continuous evaluation and improvements based on experience during global trials, a consistent and robust commercial manufacturing process for tisagenlecleucel has been developed, leading to improvements in manufacturing success when compared to the initial processes.
This study develops a definition of what mangrove-fisheries can encompass, incorporating a broad range of their possible characteristics. A detailed case study was conducted to develop a typology of ...mangrove-fishing in the Perancak Estuary, Bali, Indonesia, using interview surveys to investigate the fishing activities associated with mangroves. This case study demonstrated the complexity that a mangrove-fishery can entail, where fishing is connected to the mangrove forest by fishers of multiple sectors, functions, locations and temporal scales. Through a comparison with other mangrove-fishing communities in Bali, it also highlighted that mangrove-fisheries are variable even when in close proximity. With particular reference to this case study, a framework was developed as a flexible tool for identifying the multiple dimensions of a mangrove-fishery in a local context. Following this framework should encourage researchers and managers to look outside of the groups of fishers traditionally expected to benefit from mangrove fishing. This will enable the development of a broader definition of mangrove-fisheries in a site specific way. Identifying the full scope of fishers that contribute to or benefit from a mangrove-fishery is the first step towards building management measures that reflect the interests of groups of fishers that may otherwise remain under-represented. This is in line with international efforts for sustainability, especially in promoting small-scale fishers' access to sustainable resources under the UN Sustainable Development Goals.
Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify ...disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.
Abstract
The influence of climate change on civil conflict and societal instability in the premodern world is a subject of much debate, in part because of the limited temporal or disciplinary scope ...of case studies. We present a transdisciplinary case study that combines archeological, historical, and paleoclimate datasets to explore the dynamic, shifting relationships among climate change, civil conflict, and political collapse at Mayapan, the largest Postclassic Maya capital of the Yucatán Peninsula in the thirteenth and fourteenth centuries CE. Multiple data sources indicate that civil conflict increased significantly and generalized linear modeling correlates strife in the city with drought conditions between 1400 and 1450 cal. CE. We argue that prolonged drought escalated rival factional tensions, but subsequent adaptations reveal regional-scale resiliency, ensuring that Maya political and economic structures endured until European contact in the early sixteenth century CE.
Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through ...adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness.
To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that are modulated by the brain chemical dopamine are sensitive to reward variability. Here, we aimed to directly relate dopamine to learning about variable rewards, and the neural encoding of associated teaching signals. We perturbed dopamine in healthy individuals using dopaminergic medication and asked them to predict variable rewards while we made brain scans. Dopamine perturbations impaired learning and the neural encoding of reward variability, thus establishing a direct link between dopamine and adaptation to reward variability. These results aid our understanding of clinical conditions associated with dopaminergic dysfunction, such as psychosis.
Objective: This study aimed to assess the feasibility of implementing Individual Placement and Support (IPS) with a focus on educational and employment goals, within a clinical service for the early ...detection of individuals at clinical high risk (CHR) of psychosis. Method: Between June 2019 and April 2021, participants were recruited and received up to 6 (± 2) months support. Primary outcome: Enrolled participants, attended sessions, and disengagement rates were analyzed to assess feasibility. Secondary Outcomes: Enrollment in mainstream education or/and employment, hours spent working or/and studying, salary, level of functioning, and self-efficacy at baseline and follow-up were compared. Results: Thirty-one participants were recruited, 13 of whom were remotely recruited after the first COVID-19 lockdown. Dropout rates were relatively low (16.1%), and 26 participants (83.9%) completed the program. Each participant received on average nine sessions (M = 9.65; SD = 4.92). Secondary outcomes: At follow-up, 73.1% participants were employed, working on average more hours per week, t(25) = −2.725; p = .012, and were earning significantly more money, t(25) = −3.702; p = .001, compared to baseline. Gains in educational outcomes were less clear. Global Assessment of Functioning, t = 248.50; p = .001, and Social Occupational Functioning, t(25) = −3.273; p = .003, were significantly higher at 6-month follow-up compared to baseline. No differences were found in participants' self-efficacy. Conclusions and Implications for Practice: Findings indicate that research procedures are appropriate and that IPS implementation within a CHR clinical team is feasible. Secondary outcomes also suggest that IPS may be a beneficial intervention for young people at CHR. A longer follow-up might be needed to assess its impact on educational outcomes.
Impact and Implications
Findings from this study indicate that Individual Placement and Support (IPS) implementation within a clinical high risk (CHR) of psychosis service is feasible. Secondary outcomes also suggest that IPS may be a beneficial intervention for young people at CHR. Finally, a longer follow-up might be needed to assess its impact on educational outcomes.
PDF
