COGLE (COmmon Ground Learning and Explanation) is an explainable artificial intelligence (XAI) system for autonomous drones that deliver supplies in mountainous areas to field units. The drone missions have risks that vary with topography, flight decisions, and mission goals in a simulated environment. Users must determine which AI-controlled drone is better for a mission. Narrative explanations identify the advantages of a drone’s plan (“What?”) and reasons that the better drone is able to do them (“Why?”). Visual explanations highlight risks from obstacles that users may have overlooked (“Where?”). A model induction user study showed that post-decision explanations produced a small effect on the participants’ abilities to identify the better of two imperfect drones and their plans for a mission, but they did not teach participants to judge the multiple success factors in complex missions as well as the AI pilots. In a decision support variation of the task, users would receive pre-decision explanations to help them to decide when to trust the XAI’s decision. In a fielded XAI application, every drone available for a mission may lack some competencies. We created a proof-of-concept demonstration of automatic ways to combine knowledge from multiple imperfect AIs to get better solutions that the individual AIs do not find on their own. This paper reports on the research challenges, technical approach, and findings of the project and also reflects on the multidisciplinary journey that we took.

Quantifying how multiple ecosystem services and functions are affected by different drivers of Global Change is challenging. Particularly in African savanna regions, highly integrated land-use activities created a landscape mosaic with flows of multiple resources between land use types. A framework is needed that quantifies the effects of climate change, management and policy interventions on ecosystem services that are most relevant for rural communities, such as provision of food, feed, carbon sequestration, nutrient cycling and natural pest control. In spite of progress made in ecosystem modelling, data availability and stakeholder interactions, these elements have neither been brought together in an integrated framework, nor evaluated in the context of real-world problems. Here, we propose and outline such framework as developed by a multi-disciplinary research network, the Southern African Limpopo Landscapes network (SALLnet). Components of the framework such as the crop model APSIM and the vegetation model aDGVM2 had already been parameterized and evaluated using data sets from savanna regions of eastern, western and southern Africa, and were fine-tuned using novel data sets from Limpopo. A prototype of an agent-based farm household model was developed using comprehensive farm survey information from the Limpopo Province of South Africa. A first test of the functionality of the integrated framework has been performed for alternative policy interventions on smallholder crop-livestock systems. We discuss the versatile applicability of the framework, with a focus on smallholder landscapes in the savanna regions of southern Africa that are considered hotspots of global change impacts.

Background This systematic review used the GRADE approach to compile evidence to inform an anaphylaxis guideline from the European Academy of Allergy and Clinical Immunology (EAACI). Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18,449 participants: 29 randomised controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarised narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. Adrenaline is the cornerstone of first-line emergency management of anaphylaxis but, due to ethical constraints, little robust research has assessed its effectiveness . Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. Adrenaline prophylaxis prior to snake bite anti-venom may reduce anaphylaxis but the impact of prophylactic corticosteroids and antihistamines is uncertain. There was insufficient evidence about the impact of other anaphylaxis management strategies. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

There is growing interest in the role of structural variants (SVs) as drivers of local adaptation and speciation. From a biodiversity genomics perspective, the characterisation of genome-wide SVs provides an exciting opportunity to complement single nucleotide polymorphisms (SNPs). However, little is known about the impacts of SV discovery and genotyping strategies on the characterisation of genome-wide SV diversity within and among populations. Here, we explore a near whole-species resequence dataset, and long-read sequence data for a subset of highly represented individuals in the critically endangered kākāpō (Strigops habroptilus). We demonstrate that even when using a highly contiguous reference genome, different discovery and genotyping strategies can significantly impact the type, size and location of SVs characterised genome-wide. Further, we found that the mean number of SVs in each of two kākāpō lineages differed both within and across generations. These combined results suggest that genome-wide characterisation of SVs remains challenging at the population-scale. We are optimistic that increased accessibility to long-read sequencing and advancements in bioinformatic approaches including multi-reference approaches like genome graphs will alleviate at least some of the challenges associated with resolving SV characteristics below the species level. In the meantime, we address caveats, highlight considerations, and provide recommendations for the characterization of genome-wide SVs in biodiversity genomic research.

Social determinants of health (SDoH) may impact outcomes in sickle cell disease (SCD). We conducted a comprehensive literature review of five electronic databases to elucidate the relationship between SDoH and SCD and identify gaps in the literature. Our search yielded 59 articles which we organized into five SDoH areas: Neighborhood and Built Environment, Health and Healthcare, Social and Community Context, Education, and Economic Stability. We found that social determinants, such as access to healthcare, were inconsistently evaluated. Improved recognition and understanding of SDoH should enhance the development of programs that directly address its detrimental effects on patients with SCD.

Post renal transplant patients are generally immunosuppressed and remain at a higher risk for getting bacterial and viral infections. Most of these patients are taking immunosuppressive medications, including steroids. This case series highlights the clinical outcomes and characteristics of 8 post renal transplant patients who acquired COVID-19.

Background: Peanut allergy is among the most severe and common food allergies. The diagnosis has a significant impact on the quality of life for patients and their families. An effective management approach depends on accurate, safe, and easily implementable diagnostic methods. We previously developed a cell-based assay using Hoxb8 mast cells (Hoxb8 MCs) aimed at improving clinical allergy diagnosis. In this study we assessed its diagnostic performance by measuring blinded sera from a prospectively enrolled and pre-validated peanut allergy cohort. Methods: Hoxb8 MCs were passively sensitized with sera from peanut-allergic and peanut tolerant children and adolescents (n=96). Degranulation of Hoxb8 MCs was quantified upon stimulation with dose-titrated peanut extract by means of flow cytometry, using CD107a as activation marker. The results from the Hoxb8 mast cell activation test (Hoxb8 MAT) were compared to established diagnostic assays such as the skin prick test (SPT), specific IgE (sIgE) levels, and the basophil activation test (BAT). Additionally, serum samples from BAT non-responders were assessed with the Hoxb8 MAT. Results: Hoxb8 MAT displayed a robust dose-dependent activation to peanut extract, with a cut-off value of ≤5.2% CD107a positive cells. The diagnostic accuracy was highest at allergen concentrations ≥100 ng/ml, with an area under the receiver operating characteristic curve (AUROC) of 0.97, 93% sensitivity, and 96% specificity, outperforming traditional SPT and sIgE tests. When compared to BAT, Hoxb8 MAT exhibited comparable diagnostic efficacy. However, sera from BAT non-responders were accurately classified into allergics and non-allergics by the Hoxb8 MAT. Conclusions: The Hoxb8 MAT demonstrated a very good diagnostic precision in patients prospectively assessed for peanut allergy comparable to the fresh blood based BAT. It also demonstrated its value for accurate classification of BAT non-responders into allergic and non-allergic individuals. Further investigations into its utility in the routine clinical setting are warranted.

Banks-Leite et al. (2021) claim that our suggestion of preserving ≥40% forest cover lacks evidence and can be problematic. We find these claims unfounded, and discuss why conservation planning urgently requires valuable, well-supported, and feasible general guidelines like the 40% criterion. Using region-specific thresholds worldwide is unfeasible and potentially harmful.

1. The recovery of terrestrial carnivores in Europe is a conservation success story. Initiatives focused on restoring top predators, require information on how resident species may interact with the re-introduced species as their interactions have the potential to alter food webs, yet such data are scarce for Europe. 2. In this study, we assessed patterns of occupancy and interactions between three carnivore species in the Romanian Carpathians. Romania houses one of the few intact carnivore guilds in Europe, making it an ideal system to assess intraguild interactions, and serve as a guide for reintroductions elsewhere. 3. We used camera trap data from two seasons in Transylvanian forests to assess occupancy and co-occurrence of carnivores using multispecies occupancy models. 4. Mean occupancy in the study area was highest for lynx ( winter= 0.76 95% CI: 0.42-0.92; autumn= 0.71 CI: 0.38-0.84) and wolf (winter= 0.60 CI: 0.34-0.78; autumn= 0.81 CI: 0.25-0.95) and lowest for wildcat (winter= 0.40 CI: 0.19-0.63; autumn= 0.52 CI: 0.17-0.78) 5. We found that marginal occupancy predictors for carnivores varied between seasons. We also found differences in predictors of co-occupancy between seasons for both lynx-wolf and wildcat-wolf co-occupancy. For both seasons, we found that conditional occupancy probabilities of all three species were higher when another species was present. 6. Our results indicate that while there are seasonal differences in predictors of occupancy and co-occupancy of the three species, co-occurrence in our study area is high, and is dependent on the existence of continuous, relatively undisturbed forests. 7. Terrestrial carnivore recovery efforts are ongoing worldwide. Insights into interspecific relations between carnivore species are critical when considering the depauperate communities they are introduced in. Our work showcases that apex carnivore coexistence is possible, but dependent on protection afforded to forest habitats and their prey base.

Genomics can play important roles in biodiversity conservation, especially for Extinct-in-the-Wild species where genetic factors can influence total extinction risk and probability of successful reintroductions. The Christmas Island blue-tailed skink (Cryptoblepharus egeriae) and Lister’s gecko (Lepidodactylus listeri) are two endemic reptile species that went extinct in the wild shortly after the introduction of a predatory snake. After a decade of management, captive populations have expanded from 66 skinks and 43 geckos to several thousand individuals; however, little is known about patterns of genetic variation in these species. Here, we use PacBio HiFi long-read and Hi-C sequencing to generate contiguous reference genomes for both species, including the XY chromosome pair in the skink. We then analyze patterns of genetic diversity to infer ancient demography and more recent histories of inbreeding. We observe high genome-wide heterozygosity in the blue-tailed skink (0.007) and Lister’s gecko (0.005), consistent with large historical population sizes. However, nearly 10% of the skink reference genome falls within long runs of homozygosity (ROH), resulting in homozygosity at all major histocompatibility complex (MHC) loci, whereas we detect only a single ROH in the gecko. We infer from the ROH lengths that related skinks may have established the captive populations. Despite a shared recent extinction in the wild, our results suggest important differences in species’ histories and implications for management. We show how reference genomes can provide evolutionary and conservation insights in the absence of resequencing data, and we provide a resource for future population-level and comparative genomic studies in reptiles.

The recombinant in vitro translation system known as the PURE system has been used in a variety of cell-free experiments such as expression of native and de novo proteins as well as various display methods to select for functional polypeptides. We developed a refined PURE-based display method for the preparation of stable mRNA and cDNA-peptide conjugates and validated its utility for in vitro selection. Our conjugate formation efficiency exceeded 40%, followed by gel purification to allow minimum carry-over of components from the translation system to the downstream assay enabling clean and efficient random peptide sequence screening. As a proof-of-concept, we chose the commercially available anti-FLAG M2 antibody as a target molecule for validation. Starting from approximately 1.7 x 1012 random sequences, a round-by-round high-throughput sequencing showed clear enrichment of the FLAG epitope DYKDDD as well as revealing consensus FLAG binding motif DYK(D/L/N)(L/Y/D/N/F)D. Enrichment of core FLAG motifs lacking one of the four key residues (DYKxxD) indicates that Tyr (Y) and Lys (K) appear as the two key residues essential for binding. Furthermore, comparison between mRNA display and cDNA display method resulted in overall similar performance with slightly higher enrichment for mRNA display. The consistency of two different display methods achieved by commercially available PURE system will be useful for future studies to explore sequence and functional space of diverse polypeptides.

The nascent wave of disruptive competition in the current business environment brought about by the fourth industrial revolution (Fashion 4.0 or Apparel 4.0) is enormous. Therefore, it is paramount important to apparel industry to be flexible enough to respond quickly to the unstable customers’ demand through continuous improvement of their process efficiency and productivity. This study aims at achieving an optimal trouser assembly line balancing using simulation-based optimization via design of experiment. The empirical study is conducted at Southern Range Nyanza Limited (NYTIL) garment facility and a complex trouser assembly line with 72 operations is considered. The discrete event simulation of the trouser assembly line is developed using Arena simulation software. The local optimal solution is obtained from simulation experimentation and is adopted for the optimization process. The OptQuest tool is utilized to solve a single objective function (throughput) optimization problem. The results show that average throughput increases from the existing design (490 pieces per day) to local optimal design (638) and global optimal design (762). Consequently, the line efficiency increases from 61.2% to 79.7% to 95.2% respectively. The high increase in line efficiency and average throughput confirms the suitability assembly line balancing using simulation-based optimization via design of experiment.

Tracheoesophageal fistula (TEF) with esophageal atresia (EA) is a common congenital anomaly that is associated with significant respiratory morbidity throughout life. The objective of this document is to provide a framework for the diagnosis and management of the respiratory complications that are associated with the condition. As there are no randomized controlled studies on the subject, a group of experts used a modification of the Rand Appropriateness Method to describe the various aspects of the condition in terms of their relative importance, and to rate the available diagnostic methods and therapeutic interventions on the basis of their appropriateness and necessity. Specific recommendations were formulated and reported as Level A, B, C based on whether they were based on “strong”, “moderate” or “weak” agreement. The tracheomalacia that exists in the site of the fistula was considered the main abnormality that predisposes to all other respiratory complications due to airway collapse and impaired clearance of secretions. Aspiration due to impaired airway protection reflexes is the main underlying contributing mechanism. Flexible bronchoscopy is the main diagnostic modality, aided by imaging modalities, especially CT scans of the chest. Non-invasive positive airway pressure support, surgical techniques such as tracheopexy and rarely tracheostomy are required for the management of severe tracheomalacia. Regular long-term follow-up by a multidisciplinary team was considered imperative. Specific templates outlining the elements of the clinical respiratory evaluation according to the patients’ age were also developed.

Apicomplexan parasites comprise significant pathogens of humans, livestock, and wildlife, but also represent a diverse group of eukaryotes with interesting and unique cell biology. Study of cell biology in apicomplexan parasites is complicated by their small size, and historically this has required the application of cutting-edge microscopy techniques to investigate fundamental processes like mitosis or cell division in these organisms. Recently, a technique called expansion microscopy has been developed, which rather than increasing instrument resolution like most imaging modalities, physically expands a biological sample >4-fold. In only a few years since its development, a derivative of expansion microscopy known as ultrastructure-expansion microscopy (U-ExM) has been widely adopted and proven extremely useful for studying cell biology of Apicomplexa. Here we review the insights into apicomplexan cell biology that have been enabled through the use of U-ExM, with a specific focus on Plasmodium, Toxoplasma, and Cryptosporidium. Further, we summarise emerging expansion microscopy modifications and modalities and forecast how these may influence the field of parasite cell biology in future.

Retroviral gene delivery is widely used in T cell therapies for hematological cancers. However, viral vectors are expensive to manufacture, they integrate genes in semi-random patterns, and their transduction efficiency is highly variable. In this study, several non-viral gene delivery vehicles, promoters, and additional variables were compared to optimize non-viral transgene delivery and expression in both Jurkat and primary T cells. Overall, transfecting Jurkat cells in X-VIVOTM 15 media with Lipofectamine LTX provided a high transfection efficiency (63.0±10.9% EGFP+). However, the same method yielded a much lower transfection efficiency in primary T cells (8.1±0.8% EGFP+). Subsequent confocal microscopy revealed that a majority of the lipoplexes did not enter the primary T cells, which might be due to relatively low expression levels of heparan sulfate proteoglycans (HSPGs) detected via mRNA-sequencing. PYHIN DNA sensors (e.g., AIM2, IFI16) were also expressed at high levels in Primary T cells, which can induce apoptosis when bound to cytoplasmic DNA. Therefore, transfection of primary T cells appears to be limited at the level of cellular uptake and/or DNA sensing in the cytoplasm, so both of these factors should be considered in the development of future viral and non-viral T cell gene delivery methods.

Background: Food allergy affects up to 8% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-specific, IgE-mediated smooth muscle contractions using precision cut intestinal slices (PCIS). Methods: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0-24h. Distribution of relevant cell subsets was confirmed using single cell nuclear sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut-sensitized non-allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI-crosslinker and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed. Results: PCIS viability was maintained for 24h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen-specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE-dependent mast cell-derived mediator release. Antihistamines suppressed histamine-induced contraction and plasma from successful peanut OIT suppressed peanut-specific PCIS contraction. Conclusion: PCIS represent a novel human tissue-based model to study acute, IgE-mediated food allergy and pharmaceutical impacts on allergic responses in the gut.

Background Limited information exists on nursing home (NH) residents regarding BNT162b2/Pfizer vaccine efficacy in preventing SARS-CoV-2 and severe Covid-19, and its association with post-vaccine humoral response. Methods 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-PCR). SARS-CoV-2 Receptor-Binding Domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-PCR-positive residents, and serum neutralizing antibodies in vaccinated residents from one NH. Results The incidence of positive RT-PCR was lower in residents vaccinated by two doses (22.7%) vs one dose (32.3%) or non-vaccinated residents (43.7%)(p<0.01). Covid-19-induced deaths were observed in 10.4% of the non-vaccinated residents, in 6.4% of those who had received one dose, and in 0.9% with two doses (p=0.0007). Severe symptoms were more common in infected non-vaccinated (21.0%) vs vaccinated residents (47.6%, p=0.002). Higher levels of RBD-IgG (n=325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1,050 AU/mL. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe Covid-19. Conclusions Two BNT162b2/Pfizer doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. BNT162b2/Pfizer efficacy was partly predicted by post-vaccine RBD-IgG levels.

We report the differential diagnostic procedure and pharmacological treatment process of a case with Sluggish Cognitive Tempo (SCT) and subthreshold ADHD. The case had much more benefit from atomoxetine in terms of SCT symptoms compared to methylphenidate.