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Background:. Common peroneal nerve (CPN) disruption is the most common lower extremity nerve injury and results in gait disturbances and sensory paresthesias. The goal of this study is to describe branching patterns and the intraneural topography of the CPN to facilitate operative planning in CPN reconstruction. Methods:. The CPN and its distal motor and sensory branches were dissected in 6 lower leg cadavers. Branching patterns and distances were recorded with the fibular head as the landmark. Histological review of the nerve cross sections helped characterize the intraneural topography within the fibular tunnel. Results:. The CPN distal branching patterns were highly variable. The tibialis anterior motor branch was found on average 9.6 cm distal to the fibular head. Despite the variable branching patterns, the fascicular topography of the CPN within the fibular tunnel was consistent. Proximal to the tunnel, the nerve has 3 major fascicles, which include the superficial peroneal motor, common sensory, and deep peroneal motor (DPN) fascicles from lateral to medial. Within the tunnel, the topography consolidates into the superficial peroneal motor and DPN major divisions—motor axons anteriorly and sensory axons posteriorly. Conclusions:. The data presented provide clinically relevant information for the peripheral nerve surgeon where fascicular reconstruction of the nerve and neurolysis should focus on the anterior half of the nerve to restore ankle dorsiflexion. The nerve proximally is divided into 3 major fascicles compared with 2 distally. Surgeons may consider distal nerve transfers from the tibial nerve motor branches to the DPN or tibialis anterior motor branch.

Background/Objectives: Phyllanthus species are renowned in traditional medicine for their diverse therapeutic properties, including potential anticancer activities. This study explored the antiproliferative potential of six Phyllanthus species by integrating chemical composition with bioactivity assays to identify key antiproliferative compounds. Methods: The integration of liquid chromatography–mass spectrometry (LC-MS)-based chemical composition data with antiproliferative activity against three cancer cell lines—PC-3 (prostate adenocarcinoma), SiHa (cervical carcinoma), and A549 (lung carcinoma)—as well as a normal mouse fibroblast line (L929) was performed by covariate analysis. These compounds were subsequently isolated and structurally characterized using spectroscopic methods. Results: Through covariate statistics, seven m/z features were found to be plausible active compounds, and after isolation, they were related to butyrolactone and arylnaphthalide lignans. Among the active isolates, an unreported compound, (+)-phyllanlathyrin 6, was discovered in the aerial part of Phyllanthus lathyroides. The isolated compounds exhibited moderate to good antiproliferative activity (IC50 < 20 µM) with selectivity to SiHa, validating the covariate-based identification approach. Conclusions: These findings highlight the potential of Phyllanthus species as sources of novel anticancer agents, with specific arylnaphthalide lignans showing promising cytotoxic effects that could be further developed into therapeutic leads. Additionally, this study underscores the value of combining advanced analytical techniques with bioactivity testing to uncover bioactive compounds from natural sources. The results contribute to the growing body of evidence supporting the therapeutic relevance of Phyllanthus species and provide a foundation for future drug development efforts targeting cancer treatment.

Ionic liquid crystals have received increasing interest due to their positional and/or orientational order as well as the freedom in molecular motions that arise from the formation of mesophases between solid and liquid. While phase changes of non-fluorinated ionic liquids have been widely reported, there have been few reports on the temperature-dependent phase behavior of fluorinated ionic liquids. Here, we present a series of fluorinated ionic liquids with methylimidazolium cations bearing 1H, 1H, 2H, 2H-perfluoroalkyl chains (butyl, hexyl, and octyl) and halide counterions, and demonstrate their thermotropic mesomorphism. These cations were synthesized under solvent-free conditions, and anion exchange was used to vary the halide counterion. The thermal behavior of the compounds was studied using thermogravimetric analysis and differential scanning calorimetry, revealing both liquid crystalline phases and solid-solid phase transitions. We discovered that the mesomorphic properties of the ionic liquids depend strongly on the length of the perfluoroalkyl pendants. Specifically, ionic liquids with a fluorinated butyl chain showed no mesophase behavior while those with hexyl and octyl fluorinated chains displayed liquid crystalline phases at temperatures above 100 °C. The mesophases were further characterized by polarized optical microscopy and powder X-ray diffraction, highlighting the impact of the fluorinated alkyl chain length.

Background:. Gender-affirming breast augmentation comprises an increasing portion of breast augmentations performed by plastic surgeons. Satisfaction and breast implant illness (BII) symptoms in this population have not been well studied. This study aimed to evaluate satisfaction and BII symptoms in transwomen who received nontextured implants as part of their breast reconstruction. Methods:. We conducted a retrospective review of transwomen who underwent breast augmentation for gender-affirming surgery. We performed telephone survey evaluation using the BREAST-Q questionnaire preoperatively, 6 months and 1 year after breast implant placement. Survey evaluation asking about BII symptoms was also administered at the same time points. Results:. Twenty-six patients completed the BREAST-Q survey, which demonstrated significantly improved satisfaction postoperatively at 6 and 12 months when compared with median preoperative scores for psychosocial (P < 0.001; P < 0.001), sexual (P < 0.001; P < 0.001), and overall satisfaction with breasts (P < 0.001; P < 0.001). Physical well-being of the chest decreased at 6 months (P < 0.001) but improved in comparison with 12 months (P < 0.001). Thirty-four patients completed the BII survey, with 18% reporting symptoms at 3 months and 29% at 1 year. Zero patients requested explantation. Conclusions:. Transwomen exhibit a significant increase in breast, psychosocial, and sexual well-being after breast augmentation. However, patients experienced a decreased physical well-being, and many report symptoms associated with BII. These results can be used to better counsel these individuals preoperatively and set reasonable postoperative expectations. Further studies investigating long-term satisfaction in larger cohorts are needed.

Consumer wearables have been successful at measuring sleep and may be useful in predicting changes in mental health measures such as stress. A key challenge remains in quantifying the relationship between sleep measures associated with physiologic stress and a user's experience of stress. Students from a public university enrolled in the Lived Experiences Measured Using Rings Study (LEMURS) provided continuous biometric data and answered weekly surveys during their first semester of college between October-December 2022. We analyzed weekly associations between estimated sleep measures and perceived stress for participants (N = 525). Through mixed-effects regression models, we identified consistent associations between perceived stress scores and average nightly total sleep time (TST), resting heart rate (RHR), heart rate variability (HRV), and respiratory rate (ARR). These effects persisted after controlling for gender and week of the semester. Specifically, for every additional hour of TST, the odds of experiencing moderate-to-high stress decreased by 0.617 or by 38.3% (p

Macrophages are vital components of the immune system and serve as the first line of defense against pathogens. Macrophage colony-stimulating factor (M-CSF) induces macrophage differentiation from bone marrow-derived cells (BMDCs). Δ9-tetrahydrocannabiol (THC), a phytocannabinoid from the Cannabis plant, has profound anti-inflammatory properties with significant effects on myeloid cells. To investigate the effect of THC on macrophage differentiation, we cultured BMDCs with M-CSF in the presence of THC. Interestingly, THC markedly blocked the differentiation of BMDCs into CD45 + CD11b + F4/80+ macrophages. The effect of THC was independent of cannabinoid receptors CB1, and CB2, as well as other potential receptors such as GPR18, GPR55, and Adenosine 2A Receptor. RNA-seq analysis revealed that the THC-treated BMDCs displayed a significant increase in the expression of NRF2-ARE-related genes. KEGG pathway analysis revealed that the expression profiles of THC-treated cells correlated with ferroptosis and glutathione metabolism pathways. Fluorescence-based labile iron assays showed that the THC-treated BMDCs had significantly increased iron levels. Finally, THC-exposed BMDCs showed decreased levels of intracellular ROS. THC has the unique molecular property to block the Fenton Reaction, thus preventing the increase in intracellular ROS that is normally induced by high iron levels. Together, these studies demonstrated that THC blocks M-CSF-induced macrophage differentiation by inhibiting ROS production through both the induction of NRF2-ARE-related gene expression and the prevention of ROS formation via the Fenton Reaction.

Abstract Ecosystem change can profoundly affect human well‐being and health, including through changes in exposure to vector‐borne diseases. Deforestation has increased human exposure to mosquito vectors and malaria risk in Africa, but there is little understanding of how socioeconomic and ecological factors influence the relationship between deforestation and malaria risk. We examined these interrelationships in six sub‐Saharan African countries using demographic and health survey data linked to remotely sensed environmental variables for 11,746 children under 5 years old. We found that the relationship between deforestation and malaria prevalence varies by wealth levels. Deforestation is associated with increased malaria prevalence in the poorest households, but there was not significantly increased malaria prevalence in the richest households, suggesting that deforestation has disproportionate negative health impacts on the poor. In poorer households, malaria prevalence was 27%–33% larger for one standard deviation increase in deforestation across urban and rural populations. Deforestation is also associated with increased malaria prevalence in regions where Anopheles gambiae and Anopheles funestus are dominant vectors, but not in areas of Anopheles arabiensis. These findings indicate that deforestation is an important driver of malaria risk among the world's most vulnerable children, and its impact depends critically on often‐overlooked social and biological factors. An in‐depth understanding of the links between ecosystems and human health is crucial in designing conservation policies that benefit people and the environment.

Abstract Dengue has become one of the vector-borne diseases that affect humans worldwide. In Latin American countries, Colombia is historically one of the most affected by epidemics of this flavivirus. The underreporting of signs and symptoms of probable cases of dengue, the lack of characterization of the serotypes of the infection, and the few detailed studies of postmortem necropsies of patients are among other conditions that have delayed progress in the knowledge of the pathogenesis of the disease. This study presents the results of fragment sequencing assays on paraffin-embedded tissue samples from fatal DENV cases during the 2010 epidemic in Colombia. We found that the predominant serotype was DENV-2, with the Asian/American genotype of lineages 1 and 2. This work is one of the few reports of the circulating genotypes of dengue during the 2010 epidemic in Colombia, one of the most lethal dates in the country's history.

Abstract Background Ordered transposon-insertion collections, in which specific transposon-insertion mutants are stored as monocultures in a genome-scale collection, represent a promising tool for genetic dissection of human gut microbiota members. However, publicly available collections are scarce and the construction methodology remains in early stages of development. Results Here, we describe the assembly of a genome-scale ordered collection of transposon-insertion mutants in the model gut anaerobe Bacteroides thetaiotaomicron VPI-5482 that we created as a resource for the research community. We used flow cytometry to sort single cells from a pooled library, located mutants within this initial progenitor collection by applying a pooling strategy with barcode sequencing, and re-arrayed specific mutants to create a condensed collection with single-insertion strains covering >2500 genes. To demonstrate the potential of the condensed collection for phenotypic screening, we analyzed growth dynamics and cell morphology. We identified both growth defects and altered cell shape in mutants disrupting sphingolipid synthesis and thiamine scavenging. Finally, we analyzed the process of assembling the B. theta condensed collection to identify inefficiencies that limited coverage. We demonstrate as part of this analysis that the process of assembling an ordered collection can be accurately modeled using barcode sequencing data. Conclusion We expect that utilization of this ordered collection will accelerate research into B. theta physiology and that lessons learned while assembling the collection will inform future efforts to assemble ordered mutant collections for an increasing number of gut microbiota members.

The extracellular domain of tumor necrosis factor receptors (TNFR) generally require assembly into a homotrimeric quaternary structure as a prerequisite for initiation of signaling via the cytoplasmic domains. TNF receptor homotrimers are natively activated by similarly homo-trimerized TNF ligands, but can also be activated by synthetic agonists including engineered antibodies and Fc-ligand fusion proteins. A large body of literature from pre-clinical models supports the hypothesis that synthetic agonists targeting a diverse range of TNF receptors (including 4-1BB, CD40, OX40, GITR, DR5, TNFRSF25, HVEM, LTβR, CD27, and CD30) could amplify immune responses to provide clinical benefit in patients with infectious diseases or cancer. Unfortunately, however, the pre-clinical attributes of synthetic TNF receptor agonists have not translated well in human clinical studies, and have instead raised fundamental questions regarding the intrinsic biology of TNF receptors. Clinical observations of bell-shaped dose response curves have led some to hypothesize that TNF receptor overstimulation is possible and can lead to anergy and/or activation induced cell death of target cells. Safety issues including liver toxicity and cytokine release syndrome have also been observed in humans, raising questions as to whether those toxicities are driven by overstimulation of the targeted TNF receptor, a non-TNF receptor related attribute of the synthetic agonist, or both. Together, these clinical findings have limited the development of many TNF receptor agonists, and may have prevented generation of clinical data which reflects the full potential of TNF receptor agonism. A number of recent studies have provided structural insights into how different TNF receptor agonists bind and cluster TNF receptors, and these insights aid in deconvoluting the intrinsic biology of TNF receptors with the mechanistic underpinnings of synthetic TNF receptor agonist therapeutics.

Abstract The combined impacts of climate change and ecological degradation are expected to worsen inequality within society. These dynamics are exemplified by increases in flood risk globally. In general, low‐income and socially vulnerable populations disproportionately bear the cost of flood damages. Climate change is expected to increase the number of people exposed to fluvial flood risk and cause greater property damages. Floodplain restoration has the potential to mitigate these impacts, but the distribution of future risks among different types of property owners under these altered conditions is often unknown. Here, we develop a simple probabilistic approach for estimating flood risk to property owners under floodplain restoration and climate change scenarios for a range of flood recurrence intervals. We apply this approach in the Vermont, USA portion of the Lake Champlain Basin. Over a 100‐year time horizon, we estimate that the value of property damages caused by flood inundation is approximately $2.13 billion under the baseline scenario. Climate change is expected to increase damages to $5.29 billion, a 148% increase; however, floodplain restoration has the potential to reduce these impacts by approximately 20%. For all scenarios, a larger proportion of lower‐value properties, specifically mobile homes, face greater flood risk compared to higher‐value properties. Climate change is expected to cost higher‐value properties and commercial properties more than other types of properties, but these same groups are also expected to benefit most from floodplain restoration. In general, these results raise concern that those least able to prepare for and recover from flood damages are also the people who face the greatest threats. In response, public policy interventions must consider not only where flood risk is most severe, but also the vulnerability of people exposed to such risk. Read the free Plain Language Summary for this article on the Journal blog.

Lars Edelmann,1 Marike Hempel,2 Natalia Podsiadlo,1 Nora Schweizer,2 Cindy Tong,3 Thibaut Galvain,4 Hannah Taylor,5 Michael Schüler1 1Kantonsspital Münsterlingen, Münsterlingen, 8596, Switzerland; 2Johnson & Johnson AG, Zug, 6300, Switzerland; 3Johnson and Johnson Medical Devices, Somerville, NJ, USA; 4Johnson and Johnson Medical, Issy les Moulineaux, France; 5Johnson & Johnson Medical Limited, Berkshire, UKCorrespondence: Lars Edelmann, Klinik für Orthopädie und Traumatologie, Kantonsspital Münsterlingen, Spitalcampus 1, Münsterlingen, 8596, Switzerland, Tel +41-71-686-20 50, Fax +41-71-686-20 23, Email lars.edelmann@stgag.chPurpose: Total knee and hip arthroplasties (TKA and THA) are common surgical procedures in Switzerland and worldwide. Alongside increasing demand for these procedures, many providers have adopted enhanced recovery programs (ERPs) that aim to optimize recovery after these surgeries. We evaluated the impact of implementing a Patient Pathway Optimization (PPO) program designed around ERP principles for patients undergoing TKA or THA in a Swiss Cantonal hospital. The primary objective was to determine whether PPO implementation for patients undergoing TKA or THA reduced length of stay (LOS) during index hospitalization. Additional study outcomes were hospital inpatient costs, rate of complications and readmissions, and patient discharge destination.Methods: This was a retrospective, observational study comparing outcomes before and after PPO implementation for patients who underwent primary TKA or THA from 2014 to 2019. The PPO program modified the care pathway and implemented five ERP principles (preoperative patient education, pre-operative physiotherapy, local infiltration analgesia, early mobilization, and oral analgesia). Hospital electronic medical record and billing data were used for the analysis.Results: After implementation of PPO, LOS was shorter compared with the pre-PPO period (reduction of 2.5 and 2.4 days in TKA and THA cohorts, respectively, both p < 0.001). Mean inpatient costs per patient were also reduced following PPO (decrease of USD2016 [p = 0.015] and USD340 [p = 0.54] for TKA and THA cohorts, respectively). There were no observed increases in readmissions or complications after PPO implementation in either the TKA or THA cohort. More patients in the post-PPO groups were discharged to home vs an alternative health-care setting than in the pre-PPO groups (TKA, 83.8% vs 68.4% [p = 0.07]; THA, 80.4% vs 73.9%, [p = 0.31]).Conclusion: Patient pathway optimization and implementation of additional enhanced recovery principles for TKA and THA may benefit both health systems and patients, by reducing LOS and costs without increases in complications or readmissions.Keywords: enhanced recovery program, total hip replacement, total knee replacement, joint replacement, costs

Abstract The wildlife trade drives biodiversity loss and zoonotic disease emergence, and the health and economic impacts of COVID‐19 have sparked discussions over stricter regulation of the wildlife trade. Yet regulation for conservation and health purposes is at odds with the economic incentives provided by this multibillion‐dollar industry. To understand why the wildlife trade persists despite associated biodiversity and global health threats, we used a benefit–cost approach using simple calculations to compare the economic benefits of the wildlife trade at the individual, national, and global scales to the costs of COVID‐19, severe acute respiratory syndrome (SARS), and Ebola disease across scenarios of epidemic frequency. For COVID‐19, benefits of the wildlife trade outweigh costs at individual scales, but costs far exceed benefits at national and global scales, particularly if epidemics were to become frequent. For SARS and Ebola, benefits outweigh costs at all scales, except if Ebola‐like epidemics were to become frequent. The wildlife trade produces net benefits for people who depend on wildlife for food and income but incurs net costs on stakeholders at larger scales from increased epidemic risk. While our analysis omits a variety of costs and benefits that are difficult to quantify and contrast, our analysis is meant to illustrate the distributional outcomes across stakeholder groups that could result from increased wildlife trade regulation. Importantly, the feasibility of trade regulatory policies will depend on how these benefits and costs compare across groups and would therefore need to involve accessible and attractive alternative sources of food and livelihoods for those who depend on the wildlife trade.

Voltage-sensitive dye imaging (VSDI) is a powerful technique for measuring membrane potential dynamics of neurons but the effective resolution is limited. Here, the authors developed an in silico model of VSDI to probe activity in a biologically detailed reconstruction of rodent neocortical microcircuits.

Social inequalities may be reflected in how ecosystem services are distributed among groups of people. Here the authors estimate the distribution of three ecosystem services across demographic and socioeconomic groups in the US between 2020 and 2100, finding that non-white and lower-income groups disproportionately bear the loss of ecosystem service benefits.

Purpose: Our objectives are to assess (1) the acceptability and feasibility of dietary interventions for patients undergoing radiation therapy (RT), and (2) the impact of dietary interventions on patient reported outcomes, toxicities, and survival. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to include articles that evaluate adding dietary interventions to patients receiving RT. Acceptability was defined as (# accepting/# approached); feasibility was (# completing/# approached). Patient-reported outcomes were reported based on questionnaires used in each study and survival was measured from the date of diagnosis until death in each study. Level of evidence was assessed with Center for Evidence-Based Medicine (CEBM) criteria. Results: Sixteen articles were included; among these, 2027 patients were approached regarding the intervention, and 1661 accepted (81.9%); of these, 1543 (92.9%) completed the prescribed diet + RT course. The most common cancers included were gynecological, head and neck, and gastrointestinal. For patients with pelvic cancers, a high fiber diet may improve diarrhea (CEBM level 1b). Enteral nutrition formula, including formulas with proteins such as L-arginine, lipids such as eicosapentaenoic acids, glucids, and ribonucleotides, may help prevent of malnutrition in head and neck cancer patients undergoing RT (level 2b). Vitamin C and β-carotene may reduce of xerostomia in head and neck cancer patients; however, the studies evaluating these vitamins included vitamin E, which increases all-cause mortality (level 2b). No dietary intervention for cancer patients receiving RT has been shown to improve survival. Conclusion: There are limited data to support safe and efficacious use of dietary interventions during RT.

An autonomous and continuously operating Radio Frequency Identification (RFID) temperature sensor is designed, manufactured, and tested. This sensor is battery-free and can detect temperature threshold crossings for multiple (room-to-cold and cold-to-room) temperature cycles, respectively. The proposed sensor conveys temperature threshold crossings through the controlled switching of its operating frequency within the 902-928 MHz Ultra High Frequency (UHF) RFID band. For the first time, shape morphing cold-temperature reactive Liquid Crystal Elastomers (LCEs), which provide reversible actuation, are utilized. The proposed sensor design consists of a patch antenna with a customized slot. A passive mechanical switch is connected across this slot and provides the frequency switching as it is activated and deactivated. The integration of this switch with the antenna is achieved using a co-simulation method. Furthermore, the cold-temperature reactive LCE triggers the switch when a temperature violation has occurred, thereby switching the operating frequency of the sensor based on temperature changes. Additionally, a high-dielectric constant substrate and a single matching network that operates at two discrete frequencies are used to design our compact frequency-domain temperature sensor. Moreover, based on the RFID platform, this sensor operates effectively in close-proximity to other sensors. Also, is provides identification and temperature information through an autonomous, continuous, and cost-effective design. Therefore, the proposed sensor has the potential for operation in the Internet of Things (IoTs) applications, where large amounts of data is collected from numerous sensors to extract valuable information for the benefit of users, manufacturers, and delivery companies in the virtual domain of the internet. Finally, ANSYS HFSS and Circuit Designer are used for the simulation modeling. The performance of our sensor is validated using measurements and simulations that agree very well.

In this research, we have developed a novel temperature sensor to be utilized in the Cold-Supply-Chain (CSC) for perishable items. This sensor conveys temperature threshold crossings by switching operation between two individual RFID ICs, i.e., two individual Electronic Product Codes (EPCs). The advantage of this sensor compared to other existing technologies is that it can operate passively (i.e., battery-free) through multiple room-to-cold and cold-to-room temperature cycles, in real-time, without requiring any form of resetting. This design utilizes innovative cold-responsive liquid crystal elastomers (LCEs), which change shape when stimulated by cold temperatures and returns to a relaxed state when the stimulus is removed. In fact, this is the first temperature sensor that conveys temperature threshold crossings by switching between two RFID ICs using LCEs. The correct operation of the sensor is validated by RFID measurements. ANSYS HFSS and ANSYS Circuit Designer were used for the simulation analysis. The performance of the proposed design was validated using simulations and measurements.

Purpose – The purpose of this paper is to provide insight on high-interest areas of research in defense-related logistics and supply chain management and opportunities for advancing theory and practice in this domain. Design/methodology/approach – A panel of experts provided their insight to several questions oriented toward examining research opportunities and gaps in defense logistics research at the 2018 Academic Research Symposium of the Council of Supply Chain Management Professionals annual conference on September 30, 2018. Findings – Three overarching themes emerged from the panel discussion for advancing theory and practice in defense logistics and supply chain management, which are developing a central repository, creating publication opportunities and integrating research practice and knowledge with the greater academic community. Originality/value – Logistics and supply chain research is critical for advancing knowledge and practice in the military, as well as industrial settings. The intention in this manuscript is to provide scholars and practitioners in both settings greater awareness and potential avenues for developing synergies and processes for advancing logistics and supply chain research.

The COVID-19 pandemic disrupted the mobility patterns of a majority of Americans beginning in March 2020. Despite the beneficial, socially distanced activity offered by outdoor recreation, confusing and contradictory public health messaging complicated access to natural spaces. Working with a dataset comprising the locations of roughly 50 million distinct mobile devices in 2019 and 2020, we analyze weekly visitation patterns for 8,135 parks across the United States. Using Bayesian inference, we identify regions that experienced a substantial change in visitation in the first few weeks of the pandemic. We find that regions that did not exhibit a change were likely to have smaller populations, and to have voted more republican than democrat in the 2020 elections. Our study contributes to a growing body of literature using passive observations to explore who benefits from access to nature.

The relationship between nature contact and mental well-being has received increasing attention in recent years. While a body of evidence has accumulated demonstrating a positive relationship between time in nature and mental well-being, there have been few studies comparing this relationship in different locations over long periods of time. In this study, we analyze over 1.5 million tweets to estimate a happiness benefit, the difference in expressed happiness between in- and out-of-park tweets, for the 25 largest cities in the US by population. People write happier words during park visits when compared with non-park user tweets collected around the same time. While the words people write are happier in parks on average and in most cities, we find considerable variation across cities. Tweets are happier in parks at all times of the day, week, and year, not just during the weekend or summer vacation. Across all cities, we find that the happiness benefit is highest in parks larger than 100 acres. Overall, our study suggests the happiness benefit associated with park visitation is on par with US holidays such as Thanksgiving and New Year's Day.

The introduction of non-native species and deforestation are both important drivers of environmental change that can also facilitate the geographic spread of zoonotic pathogens and increase disease risk in humans. With ongoing trends in globalization and land-use conversions, introduced species and deforestation are ever more likely to pose threats to human health. Here, we used rat lungworm disease, an emerging zoonotic disease caused by Angiostrongylus cantonensis and maintained by invasive rats and snails, to explore how these two forms of environmental change can impact zoonotic disease risk. We used logistic regressions to examine the role of global trade in the introduction of A. cantonensis at a country level and used model estimates to predict the probability of introduction as a function of trade. We then used hurdle-based regression models to examine the association between deforestation and rat lungworm disease in two regions where A. cantonensis is already established: Hawaii and Thailand. At the global scale, we found the trade of horticultural products to be an important driver in the spread of A. cantonensis and that the majority of countries at high risk of future A. cantonensis introduction are islands. At country scales, we found deforestation to increase the per-capita risk of A. cantonensis exposure in Hawaii and Thailand. Our study provides a preliminary view of the associations between species introductions, deforestation, and risk of A. cantonensis exposure in people. Better understanding how these two widespread and overlapping forms of environmental change affect human health can inform international biosecurity protocols, invasive species management, and land-use policies.

Abstract With more people living in cities, we are witnessing a decline in exposure to nature. A growing body of research has demonstrated an association between nature contact and improved mood. Here, we used Twitter and the Hedonometer, a world analysis tool, to investigate how sentiment, or the estimated happiness of the words people write, varied before, during, and after visits to San Francisco's urban park system. We found that sentiment was substantially higher during park visits and remained elevated for several hours following the visit. Leveraging differences in vegetative cover across park types, we explored how different types of outdoor public spaces may contribute to subjective well‐being. Tweets during visits to Regional Parks, which are greener and have greater vegetative cover, exhibited larger increases in sentiment than tweets during visits to Civic Plazas and Squares. Finally, we analysed word frequencies to explore several mechanisms theorized to link nature exposure with mental and cognitive benefits. Negation words such as ‘no’, ‘not’, and ‘don't’ decreased in frequency during visits to urban parks. These results can be used by urban planners and public health officials to better target nature contact recommendations for growing urban populations. A free Plain Language Summary can be found within the Supporting Information of this article.

Summary: Human genetics studies have uncovered genetic variants that can be used to guide biological research and prioritize molecular targets for therapeutic intervention for complex diseases. We have identified a missense variant (P746S) in EDEM3 associated with lower blood triglyceride (TG) levels in >300,000 individuals. Functional analyses in cell and mouse models show that EDEM3 deficiency strongly increased the uptake of very-low-density lipoprotein and thereby reduced the plasma TG level, as a result of up-regulated expression of LRP1 receptor. We demonstrate that EDEM3 deletion up-regulated the pathways for RNA and endoplasmic reticulum protein processing and transport, and consequently increased the cell surface mannose-containing glycoproteins, including LRP1. Metabolomics analyses reveal a cellular TG accumulation under EDEM3 deficiency, a profile consistent with individuals carrying EDEM3 P746S. Our study identifies EDEM3 as a regulator of blood TG, and targeted inhibition of EDEM3 may provide a complementary approach for lowering elevated blood TG concentrations. : Genetics; Diabetology; Specialized Functions of Cells; Metabolomics Subject Areas: Genetics, Diabetology, Specialized Functions of Cells, Metabolomics

Childhood undernutrition yearly kills 3.1 million children worldwide. For those who survive early life undernutrition, it can cause motor and cognitive development problems that translate into poor educational performance and limited work productivity later in life. It has been suggested that nutrition-specific interventions (e.g., micronutrient supplementation) that directly address the immediate determinants of undernutrition (e.g., nutrient intake) need to be complemented by nutrition-sensitive interventions that more broadly address the underlying determinants of undernutrition (e.g., food insecurity). Here, we argue that forest conservation represents a potentially important but overlooked nutrition-sensitive intervention. Forests can address a number of underlying determinants of undernutrition, including the supply of forest food products, income, habitat for pollinators, women's time allocation, diarrheal disease, and dietary diversity. We examine the effects of forests on stunting—a debilitating outcome of undernutrition—using a database of household surveys and environmental variables across 25 low- and middle-income countries. Our result indicates that exposure to forest significantly reduces child stunting (at least 7.11% points average reduction). The average magnitude of the reduction is at least near the median of the impacts of other known nutrition interventions. Forest conservation interventions typically cover large areas and are often implemented where people are vulnerable, and thus could be used to reach a large number of the world's undernourished communities that may have difficult access to traditional nutrition programs. Forest conservation is therefore a potentially effective nutrition-sensitive intervention. Efforts are needed to integrate specific nutrition goals and actions into forest conservation interventions in order to unleash their potential to deliver nutritional benefits.

Abstract Simultaneous blockade of immune checkpoint molecules and co-stimulation of the TNF receptor superfamily (TNFRSF) is predicted to improve overall survival in human cancer. TNFRSF co-stimulation depends upon coordinated antigen recognition through the T cell receptor followed by homotrimerization of the TNFRSF, and is most effective when these functions occur simultaneously. To address this mechanism, we developed a two-sided human fusion protein incorporating the extracellular domains (ECD) of PD-1 and OX40L, adjoined by a central Fc domain, termed PD1-Fc-OX40L. The PD-1 end of the fusion protein binds PD-L1 and PD-L2 with affinities of 2.08 and 1.76 nM, respectively, and the OX40L end binds OX40 with an affinity of 246 pM. High binding affinity on both sides of the construct translated to potent stimulation of OX40 signaling and PD1:PD-L1/L2 blockade, in multiple in vitro assays, including improved potency as compared to pembrolizumab, nivolumab, tavolixizumab and combinations of those antibodies. Furthermore, when activated human T cells were co-cultured with PD-L1 positive human tumor cells, PD1-Fc-OX40L was observed to concentrate to the immune synapse, which enhanced proliferation of T cells and production of IL-2, IFNγ and TNFα, and led to efficient killing of tumor cells. The therapeutic activity of PD1-Fc-OX40L in established murine tumors was significantly superior to either PD1 blocking, OX40 agonist, or combination antibody therapy; and required CD4+ T cells for maximum response. Importantly, all agonist functions of PD1-Fc-OX40L are independent of Fc receptor cross-linking. Collectively, these data demonstrate a highly potent fusion protein that is part of a platform, capable of providing checkpoint blockade and TNFRSF costimulation in a single molecule, which uniquely localizes TNFRSF costimulation to checkpoint ligand positive tumor cells.

Globally diarrheal disease through contaminated water sources is a major cause of child mortality. Here, the authors compile a database of 293,362 children in 35 countries and find that upstream tree cover is linked to a lower probability of diarrheal disease and that increasing tree cover may lower mortality.

Abstract The Convention on Biological Diversity and the Nagoya Protocol display a broad international consensus for biodiversity conservation and equitable benefit sharing. Yet, the Aichi biodiversity targets show a lack of progress and thus indicate a need for additional action such as enhanced and better targeted financial resource mobilization. To date, no global financial burden‐sharing instrument has been proposed. Developing a global‐scale financial mechanism to support biodiversity conservation through intergovernmental transfers, we simulate three allocation designs: ecocentric, socioecological, and anthropocentric. We analyze the corresponding incentives needed to reach the Aichi target of terrestrial protected area coverage by 2020. Here we show that the socioecological design would provide the strongest median incentive for states which are farthest from achieving the target. Our proposal provides a novel concept for global biodiversity financing, which can serve as a starting point for more specific policy dialogues on intergovernmental burden and benefit‐sharing mechanisms to halt biodiversity loss.

To combat the potentially detrimental effects of nonresponse, most surveys repeatedly follow-up with nonrespondents, often targeting a response rate or predetermined number of completes. Each additional recruitment attempt generally brings in a new wave of data, but returns gradually diminish over the course of a static data collection protocol. This is because each subsequent wave tends to contain fewer and fewer new responses, thereby rendering smaller and smaller changes in point estimates. Consequently, point estimates calculated from the accumulating data begin to stabilize. This is the notion of phase capacity, suggesting some form of design change is warranted, such as switching modes, increasing the incentive, or simply discontinuing nonrespondent follow-up. Phase capacity testing methods that have appeared in the literature to date are generally only applicable to a single point estimate. It is unclear how to proceed if conflicting results are obtained following independent tests on two or more point estimates. The purpose of this paper is to introduce two multivariate phase capacity tests, each designed with the aim of providing a universal, yes-or-no phase capacity determination for a battery of point estimates. The two competing methods’ performance is compared via simulation and application using data from the 2011 Federal Employee Viewpoint Survey.

Many scientific researchers aspire to engage policy in their writing, but translating scientific research and findings into policy discussion often requires an understanding of the institutional complexities of legal and policy processes and actors. To examine how researchers have undertaken that challenge, we developed a set of metrics and applied them to articles published in one of the principal academic publication venues for science and policy-Science magazine's Policy Forum. We reviewed each Policy Forum article published over a five-year period (2011-15), 220 in all. For each article, we assessed the level of policy content based on presence of a stated policy proposal or position and identification of the relevant policy actors and actions, and recorded attributes such as field of science, field of policy, number of references to legal and policy sources, number of authors from law and policy institutions, and number of citations. We find that a handful of science fields dominate publication frequency, but that all fields have produced publications with high policy engagement. Of the attributes, number of references to law and policy sources is correlated positively with level of engagement, whereas number of law and policy authors was fairly constant across all depths of engagement. Surprisingly, level of policy engagement was negatively correlated with the number of citations an article subsequently received. We offer possible explanations for these results and thoughts for authors, editors, and research institutions interested in facilitating robust engagement of policy in scientific writing.

It is widely anticipated that climate change will negatively affect both food security and diet diversity. Diet diversity is especially critical for children as it correlates with macro and micronutrient intake important for child development. Despite these anticipated links, little empirical evidence has demonstrated a relationship between diet diversity and climate change, especially across large datasets spanning multiple global regions and with more recent climate data. Here we use survey data from 19 countries and more than 107 000 children, coupled with 30 years of precipitation and temperature data, to explore the relationship of climate to child diet diversity while controlling for other agroecological, geographic, and socioeconomic factors. We find that higher long-term temperatures are associated with decreases in overall child diet diversity, while higher rainfall in the previous year, compared to the long-term average rainfall, is associated with greater diet diversity. Examining six regions (Asia, Central America, North Africa, South America, Southeast Africa, and West Africa) individually, we find that five have significant reductions in diet diversity associated with higher temperatures while three have significant increases in diet diversity associated with higher precipitation. In West Africa, increasing rainfall appears to counterbalance the effect of rising temperature impacts on diet diversity. In some regions, the statistical effect of climate on diet diversity is comparable to, or greater than, other common development efforts including those focused on education, improved water and toilets, and poverty reduction. These results suggest that warming temperatures and increasing rainfall variability could have profound short- and long-term impacts on child diet diversity, potentially undermining widespread development interventions aimed at improving food security.

Environmental degradation has been associated with increased burden of diseases such as malaria, diarrhea, and malnutrition. As a result, some have argued that continuing ecosystem change could undermine successes in global health investments. Here we conduct an empirical study to investigate this concern. Child deaths due to diarrhea have more than halved since the year 2000, partly due to increased access to improved water, sanitation and hygiene (WASH). We examine how the effectiveness of a water quality treatment may vary as a function of upstream watershed condition. We use data on occurrence of diarrhea and point-of-use water treatment methods from the Demographic and Health Surveys for Haiti and Honduras. We integrate these data with a variable that reflects the influence of upstream tree cover on surface water quality. Point-of-use chlorination is significantly associated with 3.4 percentage points reduction in prevalence of diarrheal disease on average. However, we only detect a significant reduction in diarrheal prevalence when upstream watersheds are moderately forested. At low upstream tree coverage, point-of-use water chlorination does not have significant effects, suggesting that forest clearing could undermine its effectiveness at reducing childhood diarrhea. Our results suggest that forested watersheds may reduce water-borne sediments and contaminants, and thus improve raw water quality in ways that moderate the effectiveness of water quality treatment. Watershed protection should be considered in WASH investments, as deforested watersheds could undermine their effectiveness, particularly in parts of low-income countries where access to improved WASH services is challenging.

Biodiversity can enhance ecosystem services such as crop pollination. Here, Ricketts et al. synthesize 14 years of literature to show that biodiversity-ecosystem services relationships depend on the service, how services and biodiversity are each measured, and the approach used to link them.

Ruggedized stretchable electronic devices motivate the development of globally stretchable yet locally stiff materials. Here, Ware et al. programme the self-organization of liquid crystal elastomers to yield stretchable materials of homogenous composition but with spatial variation in mechanical properties.

Pattern- and frequency-reconfigurable antennas are developed using metalized liquid crystalline elastomers that can change their geometries from flat to helical shapes. The pitch angle and the number of turns in this transformation are controlled by temperature. An external heat source is applied to reshape the geometry of these antennas, thereby reconfiguring their performance. The antennas are characterized using simulations and measurements.

Stimuli-responsive materials that exhibit a mechanical response to specific biological conditions are of considerable interest for responsive, implantable medical devices. Herein, we report the synthesis, processing and characterization of oxidation-responsive liquid crystal elastomers that demonstrate programmable shape changes in response to reactive oxygen species. Direct ink writing (DIW) is used to fabricate Liquid Crystal Elastomers (LCEs) with programmed molecular orientation and anisotropic mechanical properties. LCE structures were immersed in different media (oxidative, basic and saline) at body temperature to measure in vitro degradation. Oxidation-sensitive hydrophobic thioether linkages transition to hydrophilic sulfoxide and sulfone groups. The introduction of these polar moieties brings about anisotropic swelling of the polymer network in an aqueous environment, inducing complex shape changes. 3D-printed uniaxial strips exhibit 8% contraction along the nematic director and 16% orthogonal expansion in oxidative media, while printed LCEs azimuthally deform into cones 19 times their original thickness. Ultimately, these LCEs degrade completely. In contrast, LCEs subjected to basic and saline solutions showed no apparent response. These oxidation-responsive LCEs with programmable shape changes may enable a wide range of applications in target specific drug delivery systems and other diagnostic and therapeutic tools.

Payment for hydrological services (PHS) are popular tools for conserving ecosystems and their water-related services. However, improving the spatial targeting and impacts of PHS, as well as their ability to foster synergies with other ecosystem services (ES), remain challenging. We aimed at using spatial analyses to evaluate the targeting performance of México's National PHS program in central Veracruz. We quantified the effectiveness of areas targeted for PHS in actually covering areas of high HS provision and social priority during 2003-2013. First, we quantified provisioning and spatial distributions of two target (water yield and soil retention), and one non-target ES (carbon storage) using InVEST. Subsequently, pairwise relationships among ES were quantified by using spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i) prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co-occurrences of these priority areas with those targeted by PHS; (iii) evaluating the extent to which PHS directly contribute to HS delivery; and (iv), testing if PHS targeted areas disproportionately covered areas with high ecological and social priority. We found that modelled priority areas exhibited non-random distributions and distinct spatial patterns. Our results show significant pairwise correlations between all ES suggesting synergistic relationships. However, our analysis showed a significantly lower overlap than expected and thus significant mismatches between PHS targeted areas and all types of priority areas. These findings suggest that the targeting of areas with high HS provisioning and social priority by Mexico's PHS program could be improved significantly. This study underscores: (1) the importance of using maps of HS provisioning as main targeting criteria in PHS design to channel payments towards areas that require future conservation, and (2) the need for future research that helps balance ecological and socioeconomic targeting criteria.