Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

OBJECTIVE: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment. STUDY DESIGN: Randomized, controlled, single-site, early phase II, superiority trial. SETTING: Tertiary academic medical center. PARTICIPANTS: One hundred fifty participants aged 55 to 75 years with early ARHL (severity defined as borderline to moderate) and amnestic mild cognitive impairment will be included. INTERVENTIONS: Participants will be randomized 1:1 to a best practice hearing intervention or a health education control. MAIN OUTCOME MEASURES: The primary study outcome is cognition measured by the Alzheimer Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite. Secondary outcomes include additional measures of cognition, social engagement, and brain organization/connectivity. RESULTS: Trial enrollment will begin in early 2024. CONCLUSIONS: After its completion in 2028, the EARHLI trial should offer evidence on the effect of hearing treatment versus a health education control on cognitive performance, social engagement, and brain organization/connectivity in 55- to 75-year-old community-dwelling adults with early ARHL and amnestic mild cognitive impairment.

Naturalistic Object Representations Depend on Distance and Size Cues.

Egocentric distance and real-world size are important cues for object perception and action. Nevertheless, most studies of human vision rely on two-dimensional pictorial stimuli that convey ambiguous distance and size information. Here, we use fMRI to test whether pictures are represented differently in the human brain from real, tangible objects that convey unambiguous distance and size cues. Participants directly viewed stimuli in two display formats (real objects and matched printed pictures of those objects) presented at different egocentric distances (near and far). We measured the effects of format and distance on fMRI response amplitudes and response patterns. We found that fMRI response amplitudes in the lateral occipital and posterior parietal cortices were stronger overall for real objects than for pictures. In these areas and many others, including regions involved in action guidance, responses to real objects were stronger for near vs. far stimuli, whereas distance had little effect on responses to pictures-suggesting that distance determines relevance to action for real objects, but not for pictures. Although stimulus distance especially influenced response patterns in dorsal areas that operate in the service of visually guided action, distance also modulated representations in ventral cortex, where object responses are thought to remain invariant across contextual changes. We observed object size representations for both stimulus formats in ventral cortex but predominantly only for real objects in dorsal cortex. Together, these results demonstrate that whether brain responses reflect physical object characteristics depends on whether the experimental stimuli convey unambiguous information about those characteristics. Significance Statement: Classic frameworks of vision attribute perception of inherent object characteristics, such as size, to the ventral visual pathway, and processing of spatial characteristics relevant to action, such as distance, to the dorsal visual pathway. However, these frameworks are based on studies that used projected images of objects whose actual size and distance from the observer were ambiguous. Here, we find that when object size and distance information in the stimulus is less ambiguous, these characteristics are widely represented in both visual pathways. Our results provide valuable new insights into the brain representations of objects and their various physical attributes in the context of naturalistic vision.

Nutritional care pathways in cancer patients with malignant bowel obstruction: A retrospective multi-centre study.

INTRODUCTION: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO. METHODS: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression. RESULTS: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups. CONCLUSION: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life.

How to construct liquid-crystal spectacles to control vision of real-world objects and environments.

A major challenge in studying naturalistic vision lies in controlling stimulus and scene viewing time. This is especially the case for studies using real-world objects as stimuli (rather than computerized images) because real objects cannot be "onset" and "offset" in the same way that images can be. Since the late 1980s, one solution to this problem has been to have the observer wear electro-optic spectacles with computer-controlled liquid-crystal lenses that switch between transparent ("open") and translucent ("closed") states. Unfortunately, the commercially available glasses (PLATO Visual Occlusion Spectacles) command a high price tag, the hardware is fragile, and the glasses cannot be customized. This led us to explore how to manufacture liquid-crystal occlusion glasses in our own laboratory. Here, we share the products of our work by providing step-by-step instructions for researchers to design, build, operate, and test liquid-crystal glasses for use in experimental contexts. The glasses can be assembled with minimal technical knowledge using readily available components, and they can be customized for different populations and applications. The glasses are robust, and they can be produced at a fraction of the cost of commercial alternatives. Tests of reliability and temporal accuracy show that the performance of our laboratory prototype was comparable to that of the PLATO glasses. We discuss the results of our work with respect to implications for promoting rigor and reproducibility, potential use cases, comparisons with other liquid-crystal shutter glasses, and how users can find information regarding future updates and developments.

The CX3CL1-CX3CR1 chemokine axis can contribute to tumor immune evasion and blockade with a novel CX3CR1 monoclonal antibody enhances response to anti-PD-1 immunotherapy.

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration. We generated a novel monoclonal antibody against mouse CX3CR1 that binds to CX3CR1 and blocks the CX3CL1-CX3CR1 interaction. We next explored the immune evasion strategies implemented by the CX3CL1-CX3CR1 axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of soluble mediators to attract myeloid populations, and 4) generation of tumor-inflammasome. The CX3CR1 monoclonal antibody reduces migration of tumor cells and decreases secretion of immune suppressive soluble mediators by tumor cells. In combination with anti-PD-1 immunotherapy, this CX3CR1 monoclonal antibody enhances survival in an immunocompetent mouse colon carcinoma model through a decrease in tumor-promoting myeloid populations. Thus, this axis is involved in the mechanisms of resistance to anti-PD-1 immunotherapy and the combination therapy can overcome a portion of the resistance mechanisms to anti-PD-1.

Biomediated control of colloidal silica grouting using microbial fermentation.

Colloidal silica grouting is a ground improvement technique capable of stabilizing weak problematic soils and achieving large reductions in soil hydraulic conductivities for applications including earthquake-induced liquefaction mitigation and groundwater flow control. In the conventional approach, chemical accelerants are added to colloidal silica suspensions that are introduced into soils targeted for improvement and the formation of a semi-solid silica gel occurs over time at a rate controlled by suspension chemistry and in situ geochemical conditions. Although the process has been extensively investigated, controlling the rate of gel formation in the presence of varying subsurface conditions and the limited ability of conventional methods to effectively monitor the gel formation process has posed practical challenges. In this study, a biomediated soil improvement process is proposed which utilizes enriched fermentative microorganisms to control the gelation of colloidal silica grouts through solution pH reductions and ionic strength increases. Four series of batch experiments were performed to investigate the ability of glucose fermenting microorganisms to be enriched in natural sands to induce geochemical changes capable of mediating silica gel formation and assess the effect of treatment solution composition on pH reduction behaviors. Complementary batch and soil column experiments were subsequently performed to upscale the process and explore the effectiveness of chemical, hydraulic, and geophysical methods to monitor microbial activity, gel formation, and engineering improvements. Results demonstrate that fermentative microorganisms can be successfully enriched and mediate gel formation in suspensions that would otherwise remain highly stable, thereby forgoing the need for chemical accelerants, increasing the reliability and control of colloidal silica grouting, enabling new monitoring approaches, and affording engineering enhancements comparable to conventional colloidal silica grouts.

Associations of the Informal Curriculum and Student Perceptions of Research With Family Medicine Career Choice.

BACKGROUND: The United States is facing a primary care physician shortage that is predicted to continue through the next decade. Determining why graduating medical students pursue a career in family medicine may inform efforts to help address this shortage. METHODS: Medical student responses to the Family Medicine Attitudes Questionnaire (FMAQ), a 14-item validated questionnaire developed to assess student attitudes toward family medicine, were collected at 16 US medical schools and compared to each institution's proportion of graduates entering family medicine. We also analyzed subscales of the FMAQ, including attitudes toward family medicine lifestyle, research, importance, and shortages, with respect to student choice of family medicine. We used Pearson coefficients to calculate correlations. RESULTS: Student attitudes toward family medicine careers were strongly correlated with an institution's proportion of graduates entering family medicine. Positive perceptions of family medicine research by students was the factor most strongly correlated with matching into a family medicine residency. CONCLUSION: Strengthening students' exposures and perceptions of family medicine and family medicine research may create viable opportunities for intervention by departments of family medicine and medical schools seeking to increase the number of graduates entering family medicine.

Cities can benefit from complex supply chains.

Supply chain complexity is perceived to exacerbate the supply disruptions or shocks experienced by a city. Here, we calculate two network measures of supply chain complexity based on the relative number-horizontal complexity-and relative strength-vertical complexity-of a city's suppliers. Using a large dataset of more than 1 million annual supply flows to 69 major cities in the United States for 2012-2015, we show that a trade-off pattern between horizontal and vertical complexity tends to characterize the architecture of urban supply networks. This architecture shapes the resistance of cities to supply chain shocks. We find that a city experiences less intense shocks, on average, as supplier relative diversity (horizontal complexity) increases for more technologically sophisticated products, which may serve as a mechanism for buffering cities against supply chain shocks. These results could help cities anticipate and manage their supply chain risks.

Human memory for real-world solid objects is not predicted by responses to image displays.

In experimental psychology and neuroscience, computerized image stimuli are typically used as artificial proxies for real-world objects to understand brain and behavior. Here, in a series of five experiments (n = 165), we studied human memory for objects presented as tangible solids versus computerized images. We found that recall for solids was superior to images, both immediately after learning, and after a 24-hr delay. A "realness advantage" was also evident relative to three-dimensional (3-D) stereoscopic images, and when solids were viewed monocularly, arguing against explanations based on the presence of binocular depth cues in the stimulus. Critically, memory for solids was modulated by physical distance, with superior recall for objects positioned within versus outside of observers' reach, whereas recall for images was unaffected by distance. We conclude that solids are processed quantitatively and qualitatively differently in episodic memory than are images, suggesting caution in assuming that artifice can always substitute for reality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mineralogy, morphology, and reaction kinetics of ureolytic bio-cementation in the presence of seawater ions and varying soil materials.

Microbially-induced calcium carbonate precipitation (MICP) is a bio-cementation process that can improve the engineering properties of granular soils through the precipitation of calcium carbonate (CaCO3) minerals on soil particle surfaces and contacts. The technology has advanced rapidly as an environmentally conscious soil improvement method, however, our understanding of the effect of changes in field-representative environmental conditions on the physical and chemical properties of resulting precipitates has remained limited. An improved understanding of the effect of subsurface geochemical and soil conditions on process reaction kinetics and the morphology and mineralogy of bio-cementation may be critical towards enabling successful field-scale deployment of the technology and improving our understanding of the long-term chemical permanence of bio-cemented soils in different environments. In this study, thirty-five batch experiments were performed to specifically investigate the influence of seawater ions and varying soil materials on the mineralogy, morphology, and reaction kinetics of ureolytic bio-cementation. During experiments, differences in reaction kinetics were quantified to identify conditions inhibiting CaCO3 precipitation and ureolysis. Following experiments, scanning electron microscopy, x-ray diffraction, and chemical composition analyses were employed to quantify differences in mineralogical compositions and material morphology. Ions present in seawater and variations in soil materials were shown to significantly influence ureolytic activity and precipitate mineralogy and morphology, however, calcite remained the predominant CaCO3 polymorph in all experiments with relative percentages exceeding 80% by mass in all precipitates.

Exploring Online Participation and Discussion in an Online Professional Learning Activity on Twitter.

BACKGROUND: Twitter offers opportunities to share resources, engage in online discussions, and network with other professionals. In medical education, Twitter is also being used for professional development. Little is known about the level of engagement in topical chats related to medical education. This study explores how medical educators participated and engaged in Twitter-facilitated discussion activity using #MedEdChat. METHODS: All twitter chat transcripts using the hashtag #MedEdChat from Thursday night synchronous discussions were collected between January and December 2019. A total of 37 discussion topics were included. To answer the first research question about the overall participation, descriptive statistics were used to analyze the number of participants, posts, retweets, and interactions for each week's discussion. To answer the second question about types of discussion participants engaged in during weekly chats, a combination of top-down and bottom-up coding strategy was adopted with three categories: functional, social, and content. RESULTS: This study identified five themes from #MedEdChat discussions: curriculum, faculty development, scholarship, assessment, and general medical education topics. All discussions had an average of 26 participants, with an average of 145 total posts, including 37 original posts, 52 retweets, and 56 interactions (mentions or replies using @). In terms of types of discussion, content-related tweets were most frequently posted, followed by functional and social tweets. CONCLUSION: By identifying the patterns of participation and content of discussions, preliminary findings suggest implications for future study to further explore the social interactions and knowledge building processes among online participants in the Twitter-facilitated medical education online community.

CRISPR-Cas9-mediated knockout of CYP79D1 and CYP79D2 in cassava attenuates toxic cyanogen production.

Cassava (Manihot esculenta) is a starchy root crop that supports over a billion people in tropical and subtropical regions of the world. This staple, however, produces the neurotoxin cyanide and requires processing for safe consumption. Excessive consumption of insufficiently processed cassava, in combination with protein-poor diets, can have neurodegenerative impacts. This problem is further exacerbated by drought conditions which increase this toxin in the plant. To reduce cyanide levels in cassava, we used CRISPR-mediated mutagenesis to disrupt the cytochrome P450 genes CYP79D1 and CYP79D2 whose protein products catalyze the first step in cyanogenic glucoside biosynthesis. Knockout of both genes eliminated cyanide in leaves and storage roots of cassava accession 60444; the West African, farmer-preferred cultivar TME 419; and the improved variety TMS 91/02324. Although knockout of CYP79D2 alone resulted in significant reduction of cyanide, mutagenesis of CYP79D1 did not, indicating these paralogs have diverged in their function. The congruence of results across accessions indicates that our approach could readily be extended to other preferred or improved cultivars. This work demonstrates cassava genome editing for enhanced food safety and reduced processing burden, against the backdrop of a changing climate.

Native Bacterial Community Convergence in Augmented and Stimulated Ureolytic MICP Biocementation.

Microbially induced calcite precipitation is a biomineralization process with numerous civil engineering and ground improvement applications. In replicate soil columns, the efficacy and microbial composition of soil bioaugmented with the ureolytic bacterium Sporosarcina pasteurii were compared to a biostimulation method that enriches native ureolytic soil bacteria in situ under conditions analogous to field implementation. The selective enrichment resulting from sequential stimulation treatments strongly selected for Firmicutes (>97%), with Sporosarcina and Lysinibacillus comprising 60 to 94% of high-throughput 16S rDNA sequences in each suspended community sample. Seven species of the former and two of the latter were present in greater than 10% abundance at different times, demonstrating unexpected within-genus diversity and robustness in the suspended phase of this highly selective environment. Based on longer 16S sequences, it was inferred that augmented S. pasteurii competed poorly with natural bacteria, decreasing to below detection after nine treatments, while the native microbial community was enriched to approximately that present in the stimulated columns. These analyses were corroborated by the observed convergence in bulk ureolytic rates and calcite contents between techniques. However, a 10-fold discrepancy between the observed cell density and an activity-based estimate indicates the attached community, uncharacterized despite efforts, substantially contributes to bulk behavior.

Supply chain diversity buffers cities against food shocks.

Food supply shocks are increasing worldwide1,2, particularly the type of shock wherein food production or distribution loss in one location propagates through the food supply chain to other locations3,4. Analogous to biodiversity buffering ecosystems against external shocks5,6, ecological theory suggests that food supply chain diversity is crucial for managing the risk of food shock to human populations7,8. Here we show that boosting a city's food supply chain diversity increases the resistance of a city to food shocks of mild to moderate severity by up to 15 per cent. We develop an intensity-duration-frequency model linking food shock risk to supply chain diversity. The empirical-statistical model is based on annual food inflow observations from all metropolitan areas in the USA during the years 2012 to 2015, years when most of the country experienced moderate to severe droughts. The model explains a city's resistance to food shocks of a given frequency, intensity and duration as a monotonically declining function of the city's food inflow supply chain's Shannon diversity. This model is simple, operationally useful and addresses any kind of hazard. Using this method, cities can improve their resistance to food supply shocks with policies that increase the food supply chain's diversity.

Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil.

Genomic-based surveillance on the occurrence of drug resistance and its transmission dynamics has emerged as a powerful tool for the control of tuberculosis (TB). A whole-genome sequencing approach, phenotypic testing and clinical-epidemiological investigation were used to undertake a retrospective population-based study on drug-resistant (DR)-TB in Rio Grande do Sul, the largest state in Southern Brazil. The analysis included 305 resistant Mycobacterium tuberculosis strains sampled statewide from 2011 to 2014, and covered 75.7% of all DR-TB cases identified in this period. Lineage 4 was found to be predominant (99.3%), with high sublineage-level diversity composed mainly of 4.3.4.2 [Latin American and Mediterranean (LAM)/RD174], 4.3.3 (LAM/RD115) and 4.1.2.1 (Haarlem/RD182) sublineages. Genomic diversity was also reflected in resistance of the variants to first-line drugs. A large number of distinct resistance-conferring mutations, including variants that have not been reported previously in any other setting worldwide, and 22 isoniazid-monoresistant strains with mutations described as disputed in the rpoB gene but causing rifampicin resistance generally missed by automated phenotypic tests as BACTEC MGIT. Using a cut-off of five single nucleotide polymorphisms, the estimated recent transmission rate was 55.1%, with 168 strains grouped into 28 genomic clusters. The most worrying fact concerns multi-drug-resistant (MDR) strains, of which 73.4% were clustered. Different resistance profiles and acquisition of novel mutations intraclusters revealed important amplification of resistance in the region. This study described the diversity of M. tuberculosis strains, the basis of drug resistance, and ongoing transmission dynamics across the largest state in Southern Brazil, stressing the urgent need for MDR-TB transmission control state-wide.

Optimal Allocation of Chemotherapy Schemes for Metastatic Colon Cancer in Colombia.

OBJECTIVES: This study aims to determine the optimal proportion for different chemotherapy schemes in patients with metastatic colorectal cancer who have undergone surgical resection in Colombia. METHODS: A linear programming model was used to quantify the optimal proportion of the chemotherapy schemes that maximize quality-adjusted life-years (QALYs). The model was evaluated in 6 different scenarios using parametric and dynamic optimization with different budget restriction constraints. The results were compared to the current mixture of schemes used in our country. RESULTS: The results show that 63%, 37%, and 0.8% of the population should receive the FOLFOXIRI scheme (fluorouracil + leucovorin + oxaliplatin + irinotecan), FOLFIRI (irinotecan + leucovorin + fluorouracil), and FOLFIRI plus cetuximab, respectively. With these proportions, 8734 QALYs and universal coverage of the population are obtained. In an optimistic scenario (high QALYs, low costs, and budget of $40 million), the entire population should receive the FOLFIRI scheme. A pessimistic scenario (low QALYs, high costs, and budget of $15 million) would benefit only 46% of the population with the fluorouracil plus leucovorin scheme. In the other 3 scenarios with higher budget constraints, 52%, 69%, and 86% of the population should receive FOLFIRI, respectively. Dynamic optimization revealed that FOLFIRI and FOLFOX (oxaliplatin + leucovorin + fluorouracil) schemes are more likely to generate higher QALYs with lower costs and a limited budget. CONCLUSIONS: The current use of chemotherapy schemes is not optimal. An increasing proportion of FOLFIRI, FOLFOX, and FOLFOXIRI should be used more often as schemes to treat metastatic colorectal cancer in Colombia.

Protocol for a hybrid type 2 cluster randomized trial of trauma-focused cognitive behavioral therapy and a pragmatic individual-level implementation strategy.

BACKGROUND: More than two-thirds of youth experience trauma during childhood, and up to 1 in 5 of these youth develops posttraumatic stress symptoms that significantly impair their functioning. Although trauma-focused cognitive behavior therapy (TF-CBT) has a strong evidence base, it is rarely adopted, delivered with adequate fidelity, or evaluated in the most common setting where youth access mental health services-schools. Given that individual behavior change is ultimately required for successful implementation, even when organizational factors are firmly in place, focusing on individual-level processes represents a potentially parsimonious approach. Beliefs and Attitudes for Successful Implementation in Schools (BASIS) is a pragmatic, motivationally focused multifaceted strategy that augments training and consultation and is designed to target precise mechanisms of behavior change to produce enhanced implementation and youth clinical outcomes. This study protocol describes a hybrid type 2 effectiveness-implementation trial designed to concurrently evaluate the main effects, mediators, and moderators of both the BASIS implementation strategy on implementation outcomes and TF-CBT on youth mental health outcomes. METHODS: Using a cluster randomized controlled design, this trial will assign school-based mental health (SMH) clinicians and schools to one of three study arms: (a) enhanced treatment-as-usual (TAU), (b) attention control plus TF-CBT, or (c) BASIS+TF-CBT. With a proposed sample of 120 SMH clinicians who will each recruit 4-6 youth with a history of trauma (480 children), this project will gather data across 12 different time points to address two project aims. Aim 1 will evaluate, relative to an enhanced TAU condition, the effects of TF-CBT on identified mechanisms of change, youth mental health outcomes, and intervention costs and cost-effectiveness. Aim 2 will compare the effects of BASIS against an attention control plus TF-CBT condition on theoretical mechanisms of clinician behavior change and implementation outcomes, as well as examine costs and cost-effectiveness. DISCUSSION: This study will generate critical knowledge about the effectiveness and cost-effectiveness of BASIS-a pragmatic, theory-driven, and generalizable implementation strategy designed to enhance motivation-to increase the yield of evidence-based practice training and consultation, as well as the effectiveness of TF-CBT in a novel service setting. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT04451161 . Registered on June 30, 2020.

Severe Acute Respiratory Syndrome Coronavirus-2 Pneumonia in a Newborn Treated With Remdesivir and Coronavirus Disease 2019 Convalescent Plasma.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel pandemic virus. Mounting evidence supports the possibility of vertical transmission, which at the present time appears to be rare. We report a newborn with vertically acquired SARS-CoV-2 who developed acute respiratory failure and received remdesivir and coronavirus disease 2019 convalescent plasma.

Fragility of a multilayer network of intranational supply chains.

Supply chains enable the flow of goods and services within economic systems. When mapped for the entire economy and geographic locations of a country, supply chains form a spatial web of interactions among suppliers and buyers. One way to characterize supply chains is through multiregional input-output linkages. Using a multiregional input-output dataset, we build the multilayer network of supply chains in the United States. Together with a network cascade model, the multilayer network is used to explore the propagation of economic shocks along intranational supply chains. We find that the effect of economic shocks, measured using the avalanche size or total number of collapsed nodes, varies widely depending on the geographic location and economic sector of origin of a shock. The response of the supply chains to shocks reveals a threshold-like behavior. Below a certain failure or fragility level, the avalanche size increases relatively quickly for any node in the network. Based on this result, we find that the most fragile regions tend to be located in the central United States, which are regions that tend to specialize in food production and manufacturing. The most fragile layers are chemical and pharmaceutical products, services and food-related products, which are all sectors that have been disrupted by the Coronavirus Disease 2019 (COVID-19) pandemic in the United States. The fragility risk, measured by the intersection of the fragility level of a node and its exposure to shocks, varies across regions and sectors. This suggests that interventions aiming to make the supply-chain network more robust to shocks are likely needed at multiple levels of network aggregation.

Cassava breeding and agronomy in Asia: 50 years of history and future directions.

In Asia, cassava (Manihot esculenta) is cultivated by more than 8 million farmers, driving the rural economy of many countries. The International Center for Tropical Agriculture (CIAT), in partnership with national agricultural research institutes (NARIs), instigated breeding and agronomic research in Asia, 1983. The breeding program has successfully released high-yielding cultivars resulting in an average yield increase from 13.0 t ha-1 in 1996 to 21.3 t ha-1 in 2016, with significant economic benefits. Following the success in increasing yields, cassava breeding has turned its focus to higher-value traits, such as waxy cassava, to reach new market niches. More recently, building resistance to invasive pests and diseases has become a top priority due to the emergent threat of cassava mosaic disease (CMD). The agronomic research involves driving profitability with advanced technologies focusing on better agronomic management practices thereby maintaining sustainable production systems. Remote sensing technologies are being tested for trait discovery and large-scale field evaluation of cassava. In summary, cassava breeding in Asia is driven by a combination of food and market demand with technological innovations to increase the productivity. Further, exploration in the potential of data-driven agriculture is needed to empower researchers and producers for sustainable advancement.