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The eIF4E are a family of initiation factors that bind the mRNA 5’ cap, regulating the proteome and the cellular phenotype. eIF4E1 mediates global translation and its activity is controlled via the PI3K/AKT/mTOR pathway. mTOR down-regulation results in eIF4E1 sequestration into an inactive complex with the 4E binding proteins (4EBPs). The second member, eIF4E2, regulates the translatome during hypoxia. However, the exact function of the third member, eIF4E3, has remained elusive. We have dissected its function using a range of techniques. Starting from the observation that it does not interact with 4EBP1, we demonstrate that eIF4E3 recruitment into an eIF4F complex occurs when Torin1 inhibits the mTOR pathway. Ribo-seq studies demonstrate that this complex (eIF4FS) is translationally active only during stress and that it selects specific mRNA populations based on 5’ TL (UTR) length. The interactome reveals that it associates with cellular proteins beyond the cognate initiation factors, suggesting that it may have “moon-lighting” functions. Finally, we provide evidence that cellular metabolism is altered in an eIF4E3 KO background but only upon Torin1 treatment. We propose that eIF4E3 acts as a second branch of the integrated stress response, re-programming the translatome to promote “stress resistance” and adaptation.

The dissertation examines the life narrative of Tsongkhapa Losang Dragpa (1357-1419), the influential founder of the Ganden school of Tibetan Buddhism, primarily through the lens of the bodhisattva path to enlightenment, a topic that animates much of Indian Buddhist literature and Tsongkhapa’s own writings. Over the course of five chapters, the dissertation (1) contextualizes Tsongkhapa’s social, political, and historical circumstances, the limiting factors for that narrative; (2) explores the social nature of life narratives themselves, particularly Tibetan Buddhist ones, and the many sources on which Tsongkhapa drew in creating a self in relation to the bodhisattva ideal; (3) analyses the topic of asceticism as a constellation of practices that embody traditional ideals, which the dissertation uniquely relates to both monastic and, perhaps surprisingly, tantric discipline in the construction of a bodhisattva/would-be buddha self; (4) synthesizes several themes within Tsongkhapa’s oeuvre in relation to the bodhisattva path to enlightenment, highlighting the irreducibly social nature of embodied enlightenment; and (5) proposes that Tsongkhapa’s social activities, specifically his so-called Four Great Deeds, instantiate the ideal of the enlightened self’s acting within society, specifically his context of fifteenth-century Central Tibet. The dissertation relies primarily on Tsongkhapa’s brief intellectual autobiography, Excellent Presence, his earliest biography, Haven of Faith, a number of Tsongkhapa’s systematic writings, and a variety of primary and secondary sources that contextualize elements of the historical, sociological, religious, and theoretical analyses presented throughout the five chapters. In biographies of Tibetan Buddhist figures, emphasis on the hagiographic tends to obscure the social, political, and historical contexts in which their subjects act, which in turn tends to reinforce the Weberian notion of Buddhism as an individualist path. Emphasis on individual achievement (simultaneously including yet excluding lineages, practices, philosophical positions, and so on) tends to reinforce the inverse, Foucauldian notion that this is a deliberate attempt to obscure various power struggles that actually define religious actors and institutions. In the case of Tsongkhapa, modern scholarship has tended to present the remarkable success of his Ganden school either to his individual genius in advancing (allegedly) unique philosophical positions or to social facts (e.g., his efforts at monastic reform), political facts (e.g., Phagdru dominance over rival Sakya), and historical facts (e.g., Mongol allegiance to his successors) largely unrelated to his personal charisma, erudite scholarship, or social impact. As a sort of middle way between these extremes, it is possible to locate within these contexts the specific achievements of the individual who is—according to both general Buddhist understanding and contemporary theorists in philosophy, psychology, literary studies, and sociology—deeply socialized. As social documents, life narratives, inclusive of biography and hagiography, function as indices of tradition, just as do practices of monastic and tantric asceticism, all with goals of embodying the principles articulated in the systematic literature within the social, political, and historical contexts to be transcended. This ideal, then, proves to be fully situated within social contexts, and Tsongkhapa’s Four Great Deeds instantiate it in relation to both individual achievements of asceticism and the institutionalization of communal and educational capacities to replicate the processes engendering this ideal, buddhahood. In sum, Tsongkhapa’s life narrative expresses the expectations and ideals of Tibetan Buddhist culture in a way that proves complementary to systematic presentations and to “lived” practices of monastic and tantric asceticism.

Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host’s physiological capacities; however, the identity and functional role(s) of key members of the microbiome (“core microbiome”) in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems’ capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts’ plastic and adaptive responses to environmental change requires (i) recognizing that individual host–microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions., This Essay argues that in order to truly understand how marine hosts benefit from the immense diversity of microbes, we need to expand towards long-term, multi-disciplinary research focussing on few areas of the world’s ocean that we refer to as “natural experiments,” where processes can be studied at scales that far exceed those captured in laboratory experiments.

The eIF4E are a family of initiation factors that bind the mRNA 5′ cap, regulating the proteome and the cellular phenotype. eIF4E1 mediates global translation and its activity is controlled via the PI3K/AKT/mTOR pathway. mTOR down-regulation results in eIF4E1 sequestration into an inactive complex with the 4E binding proteins (4EBPs). The second member, eIF4E2, regulates the translatome during hypoxia. However, the exact function of the third member, eIF4E3, has remained elusive. We have dissected its function using a range of techniques. Starting from the observation that it does not interact with 4EBP1, we demonstrate that eIF4E3 recruitment into an eIF4F complex occurs when Torin1 inhibits the mTOR pathway. Ribo-seq studies demonstrate that this complex (eIF4FS) is translationally active during stress and that it selects specific mRNA populations based on 5′ TL (UTR) length. The interactome reveals that it associates with cellular proteins beyond the cognate initiation factors, suggesting that it may have ‘moon-lighting’ functions. Finally, we provide evidence that cellular metabolism is altered in an eIF4E3 KO background but only upon Torin1 treatment. We propose that eIF4E3 acts as a second branch of the integrated stress response, re-programming the translatome to promote ‘stress resistance’ and adaptation.

Interactions between plants and their animal pollinators can shape processes of divergence and gene flow within associated lineages. For example, in the obligate mutualism between figs (Ficus) and fig pollinator wasps (family Agaonidae), each wasp species typically pollinates a single fig species, potentially reinforcing reproductive isolation among different wasp species. Multiple pollinator species, however, can sometimes reproduce in the same host fig species, potentially enabling hybridization and introgression between wasp species. In a community of Panamanian strangler figs (section Americana), we use genome-wide ultraconserved element (UCE) loci to estimate phylogenetic relationships and test for hybridization and gene flow among 19 pollinator species associated with 16 host fig species. Previous studies showing ongoing pollinator sharing and a history of pollinator host switching are consistent with documented genetic admixture in their host figs. Here we investigate if host sharing and a dynamic evolutionary history including host switching has also resulted in hybridization and gene flow between pollinator species. Phylogenetic analyses recover strong support for well-delimited wasp species coupled with high interspecific divergence. There is no evidence for ongoing hybridization or introgression, even among pairs of pollinator species currently reproducing within the same host. In contrast to work suggesting admixture among Panamanian host figs, we conclude hybridization and interspecific gene flow have not been important processes shaping the evolutionary history of their pollinating wasps.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 2019 (COVID-19) disease, has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used—appropriately and less appropriately—to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, often dominated by a small number of individuals, and heavily influenced by superspreading events (SSEs). The distinct transmission features of SARS-CoV-2, e.g., high stochasticity under low prevalence (as compared to other pathogens, such as influenza), and the central role played by SSEs on transmission dynamics cannot be overlooked. Many explosive SSEs have occurred in indoor settings, stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, produce processing facilities, fish factories, cruise ships, family gatherings, parties, and nightclubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity to effectively contain outbreaks with targeted interventions to eliminate SSEs. Here, we describe the different types of SSEs, how they influence transmission, empirical evidence for their role in the COVID-19 pandemic, and give recommendations for control of SARS-CoV-2., This Essay discusses how the transmission of COVID-19 is dominated by superspreading events, proposing that finding ways to cut the long tail of secondary infections is important for controlling onward transmission.

BackgroundMalaria incidence has plateaued in Sub-Saharan Africa despite Seasonal Malaria Chemoprevention’s introduction. Community health workers use a door-to-door delivery strategy to treat children with SMC drugs, but for SMC to be as effective as in clinical trials, coverage must be high over successive seasons.MethodsWe developed and used a microplanning model that ‘utilizes raster to estimate population size, generates optimal households visit itinerary, and quantifies SMC coverage based on CHWs’ time investment for treatment and walking. CHWs’ performance under current SMC deployment mode was assessed using CHWs’ tracking data and compared to microplanning in villages with varying demographics and geographies.ResultsEstimates showed that microplanning significantly reduces CHWs’ walking distance by 25%, increases the number of visited households by 36% (p < 0.001) and increases SMC coverage by 21% from 37.3% under current SMC deployment mode up to 58.3% under microplanning (p < 0.001). Optimal visit itinerary alone increased SMC coverage up to 100% in small villages whereas in larger or hard-to-reach villages, filling the gap additionally needed an optimization of the CHW ratio.ConclusionWe estimate that for a pair of CHWs, the daily optimal number of visited children (assuming 8.5mn of treatment duration per child) and walking distance should not exceed 45 and 5km respectively. Our work contributes to extend SMC coverage by 21-63% and may have broader applicability for other community health programs.

Highlights • Countries within the sub-Saharan Africa (SSA) region may experience high COVID-19 case fatality rates given limited healthcare capacity to manage critical cases and poor detection leading to delayed care-seeking. • Over the first months of the epidemic in SSA and consistent with findings from other countries globally, deceased cases tended to be majority male, over the age of 50, and have underlying comorbidities. • Delayed or no care-seeking was prevalent among deceased COVID-19 cases in Burkina Faso. • Analysis on a synthetic case population representative of demographic and health characteristics of Burkina Faso COVID-19 patients suggested that treatment with oxygen therapy or convalescent plasma reduced the odds of mortality, after adjusting for age, sex, and presence of underlying comorbid conditions. • Low-cost, scalable and sustainable strategies for COVID-19 case management in the SSA context warrant attention and investment to reduce disparity in case fatality., Background Absolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia, and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies. Methods Data from deceased cases reported across SSA through May 10, 2020 and from hospitalized cases in Burkina Faso through April 15, 2020 were analyzed. Demographic, epidemiological, and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Centre Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was derived probabilistically using distributions of age, sex, and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses. Results Across SSA, deceased cases for which demographic data are available have been predominantly male (63/103, 61.2%) and over 50 years of age (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32); hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age, and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy was significantly higher than those receiving oxygen, such as due to disruptions to standard care (OR: 2.07; 95% CI: 1.56 – 2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI: 0.24 – 0.93). Conclusions Investment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers, and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted, as data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.

Vector control has been a key component in the fight against malaria for decades, and chemical insecticides are critical to the success of vector control programs worldwide. However, increasing resistance to insecticides threatens to undermine these efforts. Understanding the evolution and propagation of resistance is thus imperative to mitigating loss of intervention effectiveness. Additionally, accelerated research and development of new tools that can be deployed alongside existing vector control strategies is key to eradicating malaria in the near future. Methods such as gene drives that aim to genetically modify large mosquito populations in the wild to either render them refractory to malaria or impair their reproduction may prove invaluable tools. Mathematical models of gene flow in populations, which is the transfer of genetic information from one population to another through migration, can offer invaluable insight into the behavior and potential impact of gene drives as well as the spread of insecticide resistance in the wild. Here, we present the first multi-locus, agent-based model of vector genetics that accounts for mutations and a many-to-many mapping cardinality of genotypes to phenotypes to investigate gene flow, and the propagation of gene drives in Anopheline populations. This model is embedded within a large scale individual-based model of malaria transmission representative of a high burden, high transmission setting characteristic of the Sahel. Results are presented for the selection of insecticide-resistant vectors and the spread of resistance through repeated deployment of insecticide treated nets (ITNs), in addition to scenarios where gene drives act in concert with existing vector control tools such as ITNs. The roles of seasonality, spatial distribution of vector habitat and feed sites, and existing vector control in propagating alleles that confer phenotypic traits via gene drives that result in reduced transmission are explored. The ability to model a spectrum of vector species with different genotypes and phenotypes in the context of malaria transmission allows us to test deployment strategies for existing interventions that reduce the deleterious effects of resistance and allows exploration of the impact of new tools being proposed or developed., Author summary Vector control interventions are essential to the success of global malaria control and elimination efforts but increasing insecticide resistance worldwide threatens to derail these efforts. Releasing genetically modified mosquitoes that use gene drives to pass on desired genes and their associated phenotypic traits to the entire population within a few generations has been proposed to address resistance and other issues such as transmission heterogeneity that can sustain malaria transmission indefinitely. While the ethics and safety of these methods are being debated, mathematical models offer an efficient way of predicting the behavior and estimating the efficacy of these interventions if deployed to specific regions facing challenges to reaching elimination. We have developed a detailed mathematical model of vector genetics where specific genomes code for physical attributes that influence transmission and are affected by the surrounding environment. This is the first model to incorporate an individual-based multi-locus genetic model into a detailed individual-based model of malaria transmission. This model opens the door to investigate a number of subtle but important questions such as the effects of small numbers of mosquitoes in a region sustaining malaria transmission during the low transmission season, and the success of gene drives in regions where extant vector control interventions could kill off gene drive mosquitoes before establishment. Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector control measures.

BackgroundHalf of global child deaths occur in sub-Saharan Africa. Understanding child mortality patterns and risk factors will help inform interventions to reduce this heavy toll. The Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso was described previously, but spatial patterns of child mortality in the district had not been studied. Similar studies in other districts indicated accessibility to health facilities as a risk factor, usually without distinction between facility types.MethodsUsing Nanoro HDSS data from 2009 to 2013, we estimated the association between under-5 mortality and accessibility to inpatient and outpatient health facilities, seasonality of death, and age group.ResultsLiving in homes 40-60 minutes and >60 minutes travel time from an inpatient facility was associated with 1.52 (95% CI: 1.13-2.06) and 1.74 (1.27-2.40) greater hazard of under-5 mortality, respectively, than living in homes ConclusionsOur results emphasize the importance of geographical accessibility to health care, and also distinguish between inpatient and outpatient facilities.

BackgroundAbsolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia, and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies.MethodsData from deceased cases reported across SSA through May 10, 2020 and from hospitalized cases in Burkina Faso through April 15, 2020 were analyzed. Demographic, epidemiological, and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Center Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was derived probabilistically using distributions of age, sex, and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses.ResultsAcross SSA, deceased cases for which demographic data are available have been predominantly male (63/103, 61.2%) and over 50 years of age (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32); hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age, and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy was significantly higher than those receiving oxygen, such as due to disruptions to standard care (OR: 2.07; 95% CI: 1.56 – 2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI: 0.24 – 0.93).ConclusionInvestment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers, and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted, as data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.

Empirical studies show that plant-soil feedbacks (PSF) can generate negative density dependent (NDD) recruitment capable of maintaining plant community diversity at landscape scales. However, the observation that common plants often exhibit relatively weaker NDD than rare plants at local scales is difficult to reconcile with the maintenance of overall plant diversity. We develop a spatially explicit simulation model that tracks the community dynamics of microbial mutualists, pathogens, and their plant hosts. We find that net PSF effects vary as a function of both host abundance and key microbial traits (e.g., host affinity) in ways that are compatible with both common plants exhibiting relatively weaker local NDD, while promoting overall species diversity. The model generates a series of testable predictions linking key microbial traits and the relative abundance of host species, to the strength and scale of PSF and overall plant community diversity., Microbial plant-soil feedbacks (PSF) are fundamentally important for plant diversity. The authors present a spatially explicit dynamic model that separates the effects of microbial mutualists and pathogens, thereby presenting a testable mechanistic framework to reconcile previously puzzling observations of the strength and direction of PSF with diversity maintenance.

In this work we determine that Not4 and Not5 of the Ccr4-Not complex modulate translation elongation dynamics and change A-site ribosome dwelling in a codon-dependent fashion. These codon-specific changes in cells lacking Not5 are very robust, independent of codon position within the mRNA, the overall mRNA codon composition, expression levels or changes of mRNA levels in the absence of Not5, but inversely correlate with those in cells depleted for eIF5A and positively with those in cells depleted for ribosome-recycling factor Rli1. Not4 ubiquitinates Rli1, but overexpressed Rli1 that fails to get ubiquitinated induces read through at poly-Arg stretches, which also occurs in absence of Rps7A ubiquitination. Not5 shows punctate cytoplasmic staining, co-purifies with ribosomes and Rli1, but not eIF5A and limits mRNA solubility. We propose that Not4 and Not5 set translation elongation dynamics to produce a soluble proteome via Rli1 and Rps7A ubiquitination, and condensates excluding eIF5A.

Background Mass drug administration (MDA) is a control and elimination tool for treating infectious diseases. For malaria, it is widely accepted that conducting MDA during the dry season results in the best outcomes. However, seasonal movement of populations into and out of MDA target areas is common in many places and could potentially fundamentally limit the ability of MDA campaigns to achieve elimination. Methods A mathematical model was used to simulate malaria transmission in two villages connected to a high-risk area into and out of which 10% of villagers traveled seasonally. MDA was given only in the villages. Prevalence reduction under various possible timings of MDA and seasonal travel was predicted. Results MDA is most successful when distributed outside the traveling season and during the village low-transmission season. MDA is least successful when distributed during the traveling season and when traveling overlaps with the peak transmission season in the high-risk area. Mistiming MDA relative to seasonal travel resulted in much poorer outcomes than mistiming MDA relative to the peak transmission season within the villages. Conclusions Seasonal movement patterns of high-risk groups should be taken into consideration when selecting the optimum timing of MDA campaigns.

Not4 and Not5 are crucial components of the Ccr4-Not complex with pivotal functions in mRNA metabolism. Both associate with ribosomes but mechanistic insights on their function remain elusive. Here we determine that Not5 and Not4 synchronously impact translation initiation and Not5 alone alters translation elongation. Deletion of Not5 causes elongation defects in a codon-dependent fashion, increasing and decreasing the ribosome dwelling occupancy at minor and major codons, respectively. This larger difference in codons’ translation velocities alters translation globally and enables kinetically unfavorable processes such as nascent chain deubiquitination to take place. In turn, this leads to abortive translation and favors protein aggregation. These findings highlight the global impact of Not4 and Not5 in controlling the speed of mRNA translation and transition from initiation to elongation.SummaryNot4 and Not5 regulate translation synchronously but distinguishably, facilitating smooth transition from initiation to elongation

The significance of symbioses between eukaryotic hosts and microbes extends from the organismal to the ecosystem level and underpins the health of Earth’s most threatened marine ecosystems. Despite rapid growth in research on host-associated microbes, from individual microbial symbionts to host-associated consortia of significantly relevant taxa, little is known about their interactions with the vast majority of marine host species. We outline research priorities to strengthen our current knowledge of host–microbiome interactions and how they shape marine ecosystems. We argue that such advances in research will help predict responses of species, communities, and ecosystems to stressors driven by human activity and inform future management strategies., The significance of symbioses between eukaryotic hosts and microbes extends from the organismal to the ecosystem level and underpins the health of Earth’s most threatened marine ecosystems. This Perspective article outlines research priorities to strengthen our current knowledge of host-microbiome interactions, to help predict responses to anthropogenic stressors and to inform future management strategies.

Maintaining zero transmission after malaria elimination will be a challenging task for many countries where malaria is still endemic. When local transmission potential is high, and importation of malaria infections continues from neighboring areas with ongoing transmission, malaria programs must develop robust surveillance and outbreak response systems. However, the requirements for such systems remain unclear. Using an agent-based, spatial microsimulation model of two areas in southern Zambia, where elimination efforts are currently underway, we compare the ability of various routine and reactive intervention packages to maintain near-zero prevalence in the face of continued importation. We find that in formerly moderate-transmission areas, high treatment rate of symptomatic malaria is sufficient to prevent reestablishment of malaria. Routine redistributions of insecticide-treated nets and reactive case detection with antimalarial drugs cannot completely compensate for inadequate case management. In formerly high-transmission areas, excellent case management and maintenance of good bednet coverage are both required to prevent resurgence, and outbreak response with antimalarial drugs or additional vector control is also necessary. These results begin to describe the essential criteria for operations that successfully prevent reestablishment of malaria post-elimination and highlight the need for both long-term, sustainable excellence in primary care and comprehensive surveillance that feeds into rapid and flexible outbreak response.Author SummaryThe global community is working toward malaria elimination, but some areas will eliminate before others. Eliminated areas will need to develop intervention programs capable of preventing imported infections from leading to reestablishment, a particular challenge when transmission was previously very high. Past experience has shown that stopping elimination interventions leads to massive resurgence, but it is unclear which interventions must be continued, which can be stopped to conserve resources, and what new interventions should be deployed. Using a simulation model built to capture malaria transmission and intervention history of two areas that recently made enormous progress toward elimination, we tested how well different intervention programs were able to prevent reestablishment of malaria. We found that treating as many symptomatic cases as possible was the single most important intervention to implement. In some contexts, this intervention alone was sufficient to prevent reestablishment. Other areas with historically higher transmission required maintaining vector control to contain mosquito populations. Localized outbreak response with antimalarial drugs or additional vector control was also necessary and predicted to be a highly efficient use of resources. These findings provide quantitative guidance for policy-makers considering how to stratify eliminated areas and plan new operational modes for the post-elimination era.

The significance of mutualisms between eukaryotic hosts and microbes extends from the organismal to the ecosystem level, and mutualistic symbioses underpin the health of Earth’s most threatened marine ecosystems. Despite rapid growth in research on host-associated microbes (microbiomes), very little is known about their interactions for the vast majority of marine host species. We outline research priorities to broaden our current knowledge of host-microbiome interactions and how they shape marine ecosystems. We argue that this research frontier will allow us to predict responses of species, communities, and ecosystems to stressors driven by human activity, and inform future management and mitigation.

BackgroundHospitalization of children with respiratory syncytial virus (RSV) is common and costly. Traditional sources of hospitalization data, useful for public health decision-makers and physicians to make decisions, are themselves costly to acquire and are subject to delays from gathering to publication. Here we use Google searches for RSV as a proxy for RSV hospitalizations.MethodsSearches for “RSV” and numbers of RSV hospitalizations in WA, MD, FL, and CT were examined from 2004–2018. Running correlation coefficients and phase angles between search and hospitalizations were calculated. Various machine learning models were compared to assess the ability of searches to forecast hospitalizations. Using search data from all 50 US states, we use K-means clustering to identify RSV transmission clusters. We calculate the timing of the optimal timing of RSV prophylaxis initiation as the week beginning the 24-week period covering 95% of all RSV cases.ResultsHigh correlations (> 0.95) and low phase differences were seen between counts of hospitalizations and search volume in WA, MD, FL, and CT. Searching for RSV began in FL and radiated outward and three distinct transmission clusters were identified: the south and northeast, the northwest and Appalachia, and the center of the country. Calculated initiation dates for prophylaxis closely followed those calculated using traditional data sources (correlation = 0.84).ConclusionsThis work validates searches as a proxy for RSV hospitalizations. Search query surveillance of RSV is a rapid and no-cost addition to traditional RSV hospitalization surveillance and may be useful for medical and public health decision-making.

Background While bed nets and insecticide spraying have had significant impact on malaria burden in many endemic regions, outdoor vector feeding and insecticide resistance may ultimately limit their contribution to elimination and control campaigns. Complementary vector control methods such as endectocides or systemic insecticides, where humans or animals are treated with drugs that kill mosquitoes upon ingestion via blood meal, are therefore generating much interest. This work explores the conditions under which long-lasting systemic insecticides would have a substantial impact on transmission and burden. Methods Hypothetical long-lasting systemic insecticides with effective durations ranging from 14 to 90 days are simulated using an individual-based mathematical model of malaria transmission. The impact of systemic insecticides when used to complement existing vector control and drug campaigns is evaluated in three settings—a highly seasonal high-transmission setting, a near-elimination setting with seasonal travel to a high-risk area, and a near-elimination setting in southern Africa. Results At 60% coverage, a single round of long-lasting systemic insecticide with effective duration of at least 60 days, distributed at the start of the season alongside a seasonal malaria chemoprevention campaign in a high-transmission setting, results in further burden reduction of 30–90% depending on the sub-populations targeted. In a near-elimination setting where transmission is sustained by seasonal travel to a high-risk area, targeting high-risk travellers with systemic insecticide with effective duration of at least 30 days can result in likely elimination even if intervention coverage is as low as 50%. In near-elimination settings with robust vector control, the addition of a 14-day systemic insecticide alongside an anti-malarial in mass drug administration (MDA) campaigns can decrease the necessary MDA coverage from about 85% to the more easily achievable 65%. Conclusions While further research into the safety profile of systemic insecticides is necessary before deployment, models predict that long-lasting systemic insecticides can play a critical role in reducing burden or eliminating malaria in a range of contexts with different target populations, existing malaria control methods, and transmission intensities. Continued investment in lengthening the duration of systemic insecticides and improving their safety profile is needed for this intervention to achieve its fullest potential.

International audience; PREMISE: Variation in pollen-ovule ratios is thought to reflect the degree of pollen transfer efficiency—the more efficient the process, the fewer pollen grains needed. Few studies have directly examined the relationship between pollen-ovule ratio and pollen transfer efficiency. For active pollination in the pollination brood mutualisms of yuccas and yucca moths, figs and fig wasps, senita and senita moths, and leafflowers and leafflower moths, pollinators purposefully collect pollen and place it directly on the stigmatic surface of conspecific flowers. The tight coupling of insect reproductive interests with pollination of the flowers in which larvae develop ensures that pollination is highly efficient.METHODS: We used the multiple evolutionary transitions between passive pollination and more efficient active pollination to test if increased pollen transfer efficiency leads to reduced pollen-ovule ratios. We collected pollen and ovule data from a suite of plant species from each of the pollination brood mutualisms and used phylogenetically controlled tests and sister-group comparisons to examine whether the shift to active pollination resulted in reduced pollen-ovule ratios.RESULTS: Across all transitions between passive and active pollination in plants, actively pollinated plants had significantly lower pollen-ovule ratios than closely related passively pollinated taxa. Phylogenetically corrected comparisons demonstrated that actively pollinated plant species had an average 76% reduction in the pollen-ovule ratio.CONCLUSIONS: The results for active pollination systems support the general utility of pollen-ovule ratios as indicators of pollination efficiency and the central importance of pollen transfer efficiency in the evolution of pollen-ovule ratio.

This chapter offers an approach to one of Thomas’s most regular forms of employment in the 1940s: public broadcasting. The BBC had always been an exacting employer, and so it proved to be for Thomas, who often complained that his contract with the Corporation afforded little room for manoeuvre. His work on-air requires special attention, however, both for the things it has to tell us about his development of voice during and after the Second World War, and for what it reveals about the BBC’s imperial politics. For as well as contributing to the Home Service, Thomas spent a good deal of the 1940s writing scripts for the Eastern Service – supposedly educating young Indian listeners, but, more often than not, getting caught up in debates about Independence. With the help of his extant Broadcasts and a series of manuscripts, this chapter assesses Thomas’s work for a poetry series called ‘Book of Verse’ – including his programme about the influence of Wilfred Owen in 1946 – and touches too on his contribution to wartime cinema.

This introduction situates Reading Dylan Thomas in three respects: in the wake of the Thomas centenary in 2014; in relation to the shifting dynamic of Thomas criticism, from the 1950s to the present; and in response to ongoing debates about reading practices. In doing so, the introduction returns to the origins of Thomas’s multimedia practice, and takes Under Milk Wood as a test case. In dwelling on this, his most well-known work, the introduction uses Thomas’s ‘play for voices’ to demonstrate both the temptations of reading him reductively – as a mouthpiece for an eccentric strain of Anglo-Welsh writing – and the peril of doing so at a time when the variousness of his art might speak otherwise to modernist scholars. As well as providing a sense of his career’s trajectory, the introduction lays the ground for the subsequent chapters by elucidating what Thomas understood by the word ‘reading’ – its requirements, pitfalls, and possibilities.