Upland Yedoma taliks are an unpredicted source of atmospheric methane.

Landscape drying associated with permafrost thaw is expected to enhance microbial methane oxidation in arctic soils. Here we show that ice-rich, Yedoma permafrost deposits, comprising a disproportionately large fraction of pan-arctic soil carbon, present an alternate trajectory. Field and laboratory observations indicate that talik (perennially thawed soils in permafrost) development in unsaturated Yedoma uplands leads to unexpectedly large methane emissions (35-78 mg m-2 d-1 summer, 150-180 mg m-2 d-1 winter). Upland Yedoma talik emissions were nearly three times higher annually than northern-wetland emissions on an areal basis. Approximately 70% emissions occurred in winter, when surface-soil freezing abated methanotrophy, enhancing methane escape from the talik. Remote sensing and numerical modeling indicate the potential for widespread upland talik formation across the pan-arctic Yedoma domain during the 21st and 22nd centuries. Contrary to current climate model predictions, these findings imply a positive and much larger permafrost-methane-climate feedback for upland Yedoma.

Thresholds for adding degraded tropical forest to the conservation estate.

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

Squamate scavenging services: Heath goannas (Varanus rosenbergi) support carcass removal and may suppress agriculturally damaging blowflies.

Human-induced environmental change has caused widespread loss of species that support important functions for ecosystems and society. For example, vertebrate scavengers contribute to the functional health of ecosystems and provide services to agricultural landscapes by removing carcasses and associated pests. Widespread extirpation of native Australian mammals since the arrival of Europeans in Australia has removed many scavenging species from landscapes, while scavenging mammals such as European red foxes (Vulpes vulpes) have been introduced. In much of Australia, squamate reptiles are the largest native terrestrial scavengers remaining, where large native mammals are extinct and conservation management is being undertaken to remove invasive mammals. The contribution of reptiles to scavenging functions is not well understood. In this study, we investigated the ecosystem functions provided by large reptiles as scavengers to better understand how populations can be managed to support ecosystem services. We investigated the ecosystem services provided by vertebrate scavengers in Australian coastal mallee ecosystems, focusing on the heath goanna (Varanus rosenbergi), the only extant native terrestrial scavenger in the region. We carried out exclosure experiments, isolating the scavenging activity of different taxonomic groups to quantify the contribution of different taxa to scavenging services, specifically the removal of rat carcasses, and its impact on the occurrence of agriculturally damaging blowflies. We compared areas with different native and invasive scavenger communities to investigate the impact of invasive species removal and native species abundance on scavenging services. Our results indicated that vertebrate scavenging significantly contributes to carcass removal and limitation of necrophagous fly breeding in carcasses and that levels of removal are higher in areas associated with high densities of heath goannas and low densities of invasive mammals. Therefore, augmentation of heath goanna populations represents a promising management strategy to restore and maximize scavenging ecosystem services.

Automated SEM analysis of particles in Hanford tank waste.

Multiple bench-scale filtration campaigns of Hanford tank waste supernatant on a backpulseable dead-end filtration skid have provided greater insight into the solids that cause fouling and reduce filter performance. The solids collected during each campaign were concentrated from the backpulse solutions and examined using automated particle analysis (APA) methods with scanning electron microscopy and X-ray energy dispersive spectroscopy to categorize particle types and their morphological characteristics. We show that with APA, thousands of particles can be analyzed to provide accurate insight into the phases that may be impacting filter performance.

The Influence of Psychosocial Factors on the Successful Formal Education Trajectories of Young Spanish People in Vulnerable Situations.

Young people in vulnerable situations tend to have more difficulties realizing successful formal education trajectories. It is extremely important to conduct studies that explore the key dimensions that can help young people overcome the conditioning of vulnerable situations, assisting in the achievement of academic success. According to the existing literature, one of these key dimensions is psychosocial well-being. Thus, this qualitative research aims to identify and analyze psychosocial factors that favor successful school pathways among young people in vulnerable situations. Through a case study approach, 12 in-depth interviews were carried out with 12 young Spanish people who not only have a vulnerable background but also successful formal education trajectories. The data were explored through qualitative content analysis-NVivo11. The results revealed that young people generally associate their successful educational trajectory with the positive impact of psychosocial factors, such as the following: positive caregivers' valuation of formal education and positive school experiences and support networks. Young people also point to many negative school experiences that have been overcome via positive attitudes and individual protective factors. The youngsters suggest changes in the educational system and teachers' skills in order to improve the levels of psychosocial support in formal education contexts. The study's implications and limitations and recommendations for future research are discussed.

In vitro and in vivo evaluation of the efficacies of commercial probiotics and disinfectant against acute hepatopancreatic necrosis disease and luminescent vibriosis in Litopenaeus vannamei.

The bioactivities of two commercially available probiotics and one chemical disinfectant were tested against strains of Vibrio parahaemolyticus (VPAHPND) and V. harveyi. This study aimed to determine shrimp pathogenic Vibrios' in vitro and in vivo sensitivities to commercial probiotics and a chemical disinfectant. The probiotics and disinfectant were tested first in vitro, followed by the in vivo trials. Results showed that upon administration of probiotics either through diet or adding into the tank water, the survivability of shrimp was increased during challenge with VPAHPND and V. harveyi. Also, the disinfectant was tested against the same pathogens and showed positive bactericidal effects at 2500 ppm and 5000 ppm. The present findings suggest that adding probiotics to the rearing water or the shrimp feeds effectively prevents infection by lowering the load of pathogenic bacteria. In comparison, the effectiveness of the disinfectant (PUR) depends on its appropriate concentration and timing of application. It is not only limited to rearing water but is also applicable for decontaminating pond liners, tanks, and other paraphernalia.

The socioecological benefits and consequences of oil palm cultivation in its native range: The Sustainable Oil Palm in West Africa (SOPWA) Project.

Agriculture is expanding rapidly across the tropics. While cultivation can boost socioeconomic conditions and food security, it also threatens native ecosystems. Oil palm (Elaeis guineensis), which is grown pantropically, is the most productive vegetable oil crop worldwide. The impacts of oil palm cultivation have been studied extensively in Southeast Asia and - to a lesser extent - in Latin America but, in comparison, very little is known about its impacts in Africa: oil palm's native range, and where cultivation is expanding rapidly. In this paper, we introduce a large-scale research programme - the Sustainable Oil Palm in West Africa (SOPWA) Project - that is evaluating the relative ecological impacts of oil palm cultivation under traditional (i.e., by local people) and industrial (i.e., by a large-scale corporation) management in Liberia. Our paper is twofold in focus. First, we use systematic mapping to appraise the literature on oil palm research in an African context, assessing the geographic and disciplinary focus of existing research. We found 757 publications occurring in 36 African countries. Studies tended to focus on the impacts of palm oil consumption on human health and wellbeing. We found no research that has evaluated the whole-ecosystem (i.e., multiple taxa and ecosystem functions) impacts of oil palm cultivation in Africa, a knowledge gap which the SOPWA Project directly addresses. Second, we describe the SOPWA Project's study design and-using canopy cover, ground vegetation cover, and soil temperature data as a case study-demonstrate its utility for assessing differences between areas of rainforest and oil palm agriculture. We outline the socioecological data collected by the SOPWA Project to date and describe the potential for future research, to encourage new collaborations and additional similar projects of its kind in West Africa. Increased research in Africa is needed urgently to understand the combined ecological and sociocultural impacts of oil palm and other agriculture in this unique region. This will help to ensure long-term sustainability of the oil palm industry-and, indeed, all tropical agricultural activity-in Africa.

Expanding the Transuranic Metal-Organic Framework Portfolio: The Optical Properties of Americium(III) MOF-76.

Reported is the synthesis, crystal structure, and solid-state characterization of a new americium containing metal-organic framework (MOF), [Am(C9H3O6)(H2O)], MOF-76(Am). This material is constructed from Am3+ metal centers and 1,3,5-tricarboxylic acid (BTC) ligands, forming a porous three-dimensional framework that is isostructural with several known trivalent lanthanide (Ln) analogs (e.g., Ce, Nd, and Sm-Lu). The Am3+ ions have seven coordinates and assume a distorted, capped trigonal prismatic geometry with C1 symmetry. The Am3+-O bonds were studied via infrared spectroscopy and compared to several MOF-76(Ln) analogs, where Ln = Nd3+, Eu3+, Tb3+, and Ho3+. The results show that the strength of the ligand carboxylate stretching and bending modes increase with Nd3+ < Eu3+ < Am3+ < Tb3+ < Ho3+, suggesting the metal-oxygen bonds are predominantly ionic. Optical absorbance spectroscopy measurements reveal strong f-f transitions; some exhibit pronounced crystal field splitting. The photoluminescence spectrum contains weak Am3+-based emission that is achieved through direct and indirect metal center excitation. The weak emissive behavior is somewhat surprising given that ligand-to-metal resonance energy transfer is efficient in the isoelectronic Eu3+ (4f6) and related Tb3+ (4f8) analogs. The optical properties were explored further within a series of heterometallic MOF-76(Tb1-xAmx) (x = 0.8, 0.2, and 0.1) samples, and the results reveal enhanced Am3+ photoluminescence.

Day-flying lepidoptera larvae have a poorer ability to thermoregulate than adults.

Changes to ambient temperatures under climate change may detrimentally impact small ectotherms that rely on their environment for thermoregulation; however, there is currently a limited understanding of insect larval thermoregulation. As holometabolous insects, Lepidoptera differ in morphology, ecology and behaviour across the life cycle, and so it is likely that adults and larvae differ in their capacity to thermoregulate. In this study, we investigated the thermoregulatory capacity (buffering ability) of 14 species of day-flying Lepidoptera, whether this is influenced by body length or gregariousness, and whether it differs between adult and larval life stages. We also investigated what thermoregulation mechanisms are used: microclimate selection (choosing locations with a particular temperature) or behavioural thermoregulation (controlling temperature through other means, such as basking). We found that Lepidoptera larvae differ in their buffering ability between species and body lengths, but gregariousness did not influence buffering ability. Larvae are worse at buffering themselves against changes in air temperature than adults. Therefore Lepidoptera may be more vulnerable to adverse temperature conditions during their larval life stage. Adults and larvae rely on different thermoregulatory mechanisms; adults primarily use behavioural thermoregulation, whereas larvae use microclimate selection. This implies that larvae are highly dependent on the area around their foodplant for effective thermoregulation. These findings have implications for the management of land and species, for example, highlighting the importance of creating and preserving microclimates and vegetation complexity surrounding Lepidoptera foodplants for larval thermoregulation under future climate change.

Complete genome sequence of Vibrio parahaemolyticus strain PH1273, isolated from aquacultured shrimp in the Philippines.

We announce the complete genome sequence of Vibrio parahaemolyticus strain PH1273. This strain was collected from a Penaeus vannamei pond in the Philippines in 2015. Genome analysis revealed that it lacks the gene pirAB responsible for causing acute hepatopancreatic necrosis disease but encode multiple secretion systems and the associated effectors.

Tropical butterflies use thermal buffering and thermal tolerance as alternative strategies to cope with temperature increase.

Climate change poses a severe threat to many taxa, with increased mean temperatures and frequency of extreme weather events predicted. Insects can respond to high temperatures using behaviour, such as angling their wings away from the sun or seeking cool local microclimates to thermoregulate or through physiological tolerance. In a butterfly community in Panama, we compared the ability of adult butterflies from 54 species to control their body temperature across a range of air temperatures (thermal buffering ability), as well as assessing the critical thermal maxima for a subset of 24 species. Thermal buffering ability and tolerance were influenced by family, wing length, and wing colour, with Pieridae, and butterflies that are large or darker in colour having the strongest thermal buffering ability, but Hesperiidae, small, and darker butterflies tolerating the highest temperatures. We identified an interaction between thermal buffering ability and physiological tolerance, where species with stronger thermal buffering abilities had lower thermal tolerance, and vice versa. This interaction implies that species with more stable body temperatures in the field may be more vulnerable to increases in ambient temperatures, for example heat waves associated with ongoing climate change. Our study demonstrates that tropical species employ diverse thermoregulatory strategies, which is also reflected in their sensitivity to temperature extremes.

El cambio climático representa una grave amenaza para muchos taxones, con un aumento de las temperaturas medias y la frecuencia de eventos climáticos extremos pronosticados. Los insectos pueden responder a las altas temperaturas mediante comportamientos, como inclinar sus alas fuera del alcance del sol o buscar microclimas frescos locales para termorregular, o a través de la tolerancia fisiológica. En una comunidad de mariposas en Panamá, comparamos la capacidad de las mariposas adultas de 54 especies para controlar su temperatura corporal en un rango de temperaturas del aire (capacidad de amortiguación térmica), así como evaluar el máximo térmico crítico para un subconjunto de 24 especies. La capacidad de amortiguación térmica y la tolerancia se influenciaron por la familia, la longitud del ala y el colour del ala; con Pieridae y mariposas grandes o de colour más oscuro teniendo la capacidad de amortiguación térmica más fuerte, pero Hesperiidae, mariposas pequeñas y de colour más oscuro tolerando las temperaturas más altas. Identificamos una relación entre la capacidad de amortiguación térmica y la tolerancia fisiológica, en la que las especies con mayores capacidades de amortiguación térmica tenían una menor tolerancia térmica, y viceversa. Esta interacción implica que las especies con temperaturas corporales más estables en el campo pueden ser más vulnerables a los aumentos en las temperaturas ambientales, por ejemplo, las olas de calor asociadas con el cambio climático actual. Nuestra investigación demuestra que las especies tropicales emplean diversas estrategias de termorregulación, las cuales también se reflejan en su sensibilidad a las temperaturas extremas.

What can drawings tell us about children's perceptions of nature?

The growing disconnect between children and nature has led to concerns around the loss of ecological knowledge and reduced nature connection. Understanding children's perceptions of nature is vital for engaging them with local wildlife and mitigating this growing disconnect. This study investigated children's perceptions of nature by analysing 401 drawings made by children (aged 7-11) of their local green spaces, collected from 12 different English schools, including state-funded and privately funded. We assessed which animal and plant groups were drawn the most and least often, quantified each drawing's species richness and community composition, and identified all terms used in the drawings to the highest taxonomic resolution possible. The most commonly drawn groups were mammals (80.5% of drawings) and birds (68.6% of drawings), while herpetofauna were the least commonly drawn (15.7% of drawings). Despite not explicitly being asked about plants, 91.3% of drawings contained a plant. Taxonomic resolution was highest for mammals and birds, with 90% of domestic mammals and 69.6% of garden birds identifiable to species, compared to 18.5% of insects and 14.3% of herpetofauna. No invertebrates other than insects were identifiable to species. Within plants, trees and crops were the most identifiable to species, at 52.6% and 25% of terms respectively. Drawings from state-school children had higher plant richness than those from private-school children. Animal community composition differed between school funding types, with more types of garden birds drawn by private-school than state-school children, and more types of invertebrates drawn by state-school than private-school children. Our findings indicate that children's perceptions of local wildlife are focused on mammals and birds. While plants feature prominently, plant knowledge is less specific than animal knowledge. We suggest that this skew in children's ecological awareness be addressed through better integration of ecology within national curricula and more funding for green space within schools.

Thermoregulatory ability and mechanism do not differ consistently between neotropical and temperate butterflies.

Climate change is a major threat to species worldwide, yet it remains uncertain whether tropical or temperate species are more vulnerable to changing temperatures. To further our understanding of this, we used a standardised field protocol to (1) study the buffering ability (ability to regulate body temperature relative to surrounding air temperature) of neotropical (Panama) and temperate (the United Kingdom, Czech Republic and Austria) butterflies at the assemblage and family level, (2) determine if any differences in buffering ability were driven by morphological characteristics and (3) used ecologically relevant temperature measurements to investigate how butterflies use microclimates and behaviour to thermoregulate. We hypothesised that temperate butterflies would be better at buffering than neotropical butterflies as temperate species naturally experience a wider range of temperatures than their tropical counterparts. Contrary to our hypothesis, at the assemblage level, neotropical species (especially Nymphalidae) were better at buffering than temperate species, driven primarily by neotropical individuals cooling themselves more at higher air temperatures. Morphology was the main driver of differences in buffering ability between neotropical and temperate species as opposed to the thermal environment butterflies experienced. Temperate butterflies used postural thermoregulation to raise their body temperature more than neotropical butterflies, probably as an adaptation to temperate climates, but the selection of microclimates did not differ between regions. Our findings demonstrate that butterfly species have unique thermoregulatory strategies driven by behaviour and morphology, and that neotropical species are not likely to be more inherently vulnerable to warming than temperate species.

El calentamiento global es una gran amenaza para las especies alrededor del mundo, sin embargo, no se tiene bien definido sí en los insectos, las especies distribuídas en las zonas tropicales son más vulnerables a los cambios de temperature que las especies de zonas templadas o viceversa. Para responder a este interrogante, utilizamos un protocolo de campo estandarizado aplicado a especies de mariposas distribuídas en zonas tropicales (Panamá) versus zonas templadas (Reino Unido, República Checa y Austria), con el cual buscamos: (1) Evaluar la capacidad de amortiguación (capacidad de regular la temperatura corporal en relación con la temperatura del aire circundante) en el a nivel de ensamblaje y familia, (2) Determinar sí las diferencias en la capacidad de amortiguación es facilitada por sus características morfológicas, y (3) Investigar cómo las mariposas usan los microclimas y el comportamiento para termorregularse a tráves de mediciones de temperatura ecológicamente relevantes. Nuestra hipotesis incial soportaba que las mariposas templadas estaban adaptadas para amortiguar los cambios de temperatura en comparación con las mariposas neotropicales, ya que las especies templadas experimentan un rango más amplio de temperaturas que sus contrapartes tropicales. Contrariamente a nuestra hipótesis, a nivel de ensamble, las especies neotropicales (especialmente familia Nymphalidae) fueron mejores en la capaicidad de amortiguacion que las especies templadas, explicado por el hecho de que individuos se enfrían más a altas temperaturas del aire. Así, la morfología fué el principal impulsor de las diferencias en la capacidad de amortiguación entre las especies neotropicales y templadas en comparación con el ambiente térmico experimentado por las mismas. Encontramos que las mariposas templadas utilizaron la termorregulación de postura para elevar su temperatura corporal más que las mariposas neotropicales, probablemente como una adaptación a los climas templados, aunque la selección de microclimas no difirió entre regiones. Nuestros hallazgos demuestran que las especies de mariposas tienen estrategias de termorregulación únicas, impulsadas principalmente por el comportamiento y morfología, además nuestros resultados demuestran que a diferencia de lo que se ha pensado, las especies neotropicales son igual de vulnerables al calentamiento de su hábitat que las especies templadas.

Genomic analysis of Vibrio harveyi strain PH1009, a potential multi-drug resistant pathogen due to acquisition of toxin genes.

In has increasingly been observed that viral and bacterial coinfection frequently occurs among cultured shrimp and this coinfection could exacerbate the disease phenotype. Here, we describe a newly discovered bacterial strain, Vibrio harveyi PH1009 collected from Masbate Island, Philippines that was found to be co-infecting with the White Spot Syndrome virus in a sample of black tiger prawn, Penaeus monodon. The genome of V. harveyi PH1009 was sequenced, assembled, and annotated. Average Nucleotide identity calculation with Vibrio harveyi strains confirmed its taxonomic identity. It is a potential multi-drug and multi-heavy metal resistant strain based on the multiple antibiotic and heavy metal resistance determinants annotated on its genome. Two prophage regions were identified in its genome. One contained genes for Zona occludens toxin (Zot) and Accessory cholera toxin (Ace), essential toxins of toxigenic V. cholerae strains apart from CTX toxins. Pan-genome analysis of V. harveyi strains, including PH1009, revealed an "open" pan-genome for V. harveyi and a core genome mainly composed of genes necessary for growth and metabolism. Phylogenetic tree based on the core genome alignment revealed that PH1009 was closest to strains QT520, CAIM 1754, and 823tez1. Published virulence factors present on the strain QT520 suggest similar pathogenicity with PH1009. However, PH1009 Zot was not found on related strains but was present in strains HENC-01 and CAIM 148. Most unique genes found in the PH1009 strain were identified as hypothetical proteins. Further annotation showed that several of these hypothetical proteins were phage transposases, integrases, and transcription regulators, implying the role of bacteriophages in the distinct genomic features of the PH1009 genome. The PH1009 genome will serve as a valuable genomic resource for comparative genomic studies and in understanding the disease mechanism of the Vibrio harveyi species.

Insight into the Structural and Emissive Behavior of a Three-Dimensional Americium(III) Formate Coordination Polymer.

We report the structural, vibrational, and optical properties of americium formate (Am(CHO2 )3 ) crystals synthesized via the in situ hydrolysis of dimethylformamide (DMF). The coordination polymer features Am3+ ions linked by formate ligands into a three-dimensional network that is isomorphous to several lanthanide analogs, (e. g., Eu3+ , Nd3+ , Tb3+ ). Structure determination revealed a nine-coordinate Am3+ metal center that features a unique local C3v symmetry. The metal-ligand bonding interactions were investigated by vibrational spectroscopy, natural localized molecular orbital calculations, and the quantum theory of atoms in molecules. The results paint a predominantly ionic bond picture and suggest the metal-oxygen bonds increase in strength from Nd-O

Tropical forests post-logging are a persistent net carbon source to the atmosphere.

Logged and structurally degraded tropical forests are fast becoming one of the most prevalent land-use types throughout the tropics and are routinely assumed to be a net carbon sink because they experience rapid rates of tree regrowth. Yet this assumption is based on forest biomass inventories that record carbon stock recovery but fail to account for the simultaneous losses of carbon from soil and necromass. Here, we used forest plots and an eddy covariance tower to quantify and partition net ecosystem CO2 exchange in Malaysian Borneo, a region that is a hot spot for deforestation and forest degradation. Our data represent the complete carbon budget for tropical forests measured throughout a logging event and subsequent recovery and found that they constitute a substantial and persistent net carbon source. Consistent with existing literature, our study showed a significantly greater woody biomass gain across moderately and heavily logged forests compared with unlogged forests, but this was counteracted by much larger carbon losses from soil organic matter and deadwood in logged forests. We estimate an average carbon source of 1.75 ± 0.94 Mg C ha-1 yr-1 within moderately logged plots and 5.23 ± 1.23 Mg C ha-1 yr-1 in unsustainably logged and severely degraded plots, with emissions continuing at these rates for at least one-decade post-logging. Our data directly contradict the default assumption that recovering logged and degraded tropical forests are net carbon sinks, implying the amount of carbon being sequestered across the world's tropical forests may be considerably lower than currently estimated.

ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aß Oligomers: Development Rationale, Phase 1 Trial Design, and Clinical Development Plan.

BACKGROUND: Alzheimer's disease is a large and growing unmet medical need. Clinical trial designs need to assess disease-related outcomes earlier to accelerate the development of better treatments for Alzheimer's disease. ACU193 is a monoclonal antibody that selectively targets amyloid ß oligomers, thought to be the most toxic species of Aß that accumulates early in AD and contributes to downstream pathological effects. Nonclinical data indicate that ACU193 can reduce the toxic effects of amyloid ß oligomers. ACU193 is currently being investigated in a phase 1 clinical trial designed with the properties described in this report. This phase 1 trial is designed to provide data to enable a go/no-go decision regarding the initiation of a subsequent phase 2/3 study. OBJECTIVES: To design a phase 1 study that assesses target engagement and incorporates novel measures to support more rapid development of a potential disease-modifying treatment for Alzheimer's disease. DESIGN: The INTERCEPT-AD trial for ACU193 is an ongoing randomized, placebo-controlled phase 1a/b study that assesses safety, tolerability, pharmacokinetics, target engagement, clinical measures, and several Alzheimer's disease biomarkers, including novel digital and imaging biomarkers. SETTING: For INTERCEPT-AD, brief inpatient stays for patients in the single ascending dose portion of the study, with the remainder of the evaluations being performed as outpatients at multiple clinical trial sites in the U.S. PARTICIPANTS: Patients with early Alzheimer's disease (mild cognitive impairment or mild dementia with a positive florbetapir positron emission tomography scan). INTERVENTION: ACU193 administered intravenously at doses of 2- 60 mg/kg. MEASUREMENTS: Safety assessments including magnetic resonance imaging for the presence of amyloid-related imaging abnormalities, clinical assessments for Alzheimer's disease including the Alzheimer's Disease Rating Scale-cognition and Clinical Dementia Rating scale, pharmacokinetics, a measure of target engagement, and digital and imaging biomarkers, including a computerized cognitive test battery and a measure of cerebral blood flow using arterial spin labelling magnetic resonance imaging. RESULTS: A phase 1 study design was developed for ACU193 that allows collection of data that will enable a go/no-go decision for initiation of a subsequent adaptive phase 2/3 study. CONCLUSIONS: A phase 1a/b trial and an overall clinical development plan for an Alzheimer's disease treatment can be designed that maintains patient safety, allows informed decision-making, and achieves an accelerated timeline by using novel biomarkers and adaptive study designs.