Upper Blue Nile Basin Water Budget from a Multi-Model Perspective.

Improved understanding of the water balance in the Blue Nile is of critical importance because of increasingly frequent hydroclimatic extremes under a changing climate. The intercomparison and evaluation of multiple land surface models (LSMs) associated with different meteorological forcing and precipitation datasets can offer a moderate range of water budget variable estimates. In this context, two LSMs, Noah version 3.3 (Noah3.3) and Catchment LSM version Fortuna 2.5 (CLSMF2.5) coupled with the Hydrological Modeling and Analysis Platform (HyMAP) river routing scheme are used to produce hydrological estimates over the region. The two LSMs were forced with different combinations of two reanalysis-based meteorological datasets from the Modern-Era Retrospective analysis for Research and Applications datasets (i.e., MERRA-Land and MERRA-2) and three observation-based precipitation datasets, generating a total of 16 experiments. Modeled evapotranspiration (ET), streamflow, and terrestrial water storage estimates were evaluated against the Atmosphere-Land Exchange Inverse (ALEXI) ET, in-situ streamflow observations, and NASA Gravity Recovery and Climate Experiment (GRACE) products, respectively. Results show that CLSMF2.5 provided better representation of the water budget variables than Noah3.3 in terms of Nash-Sutcliffe coefficient when considering all meteorological forcing datasets and precipitation datasets. The model experiments forced with observation-based products, the Climate Hazards group Infrared Precipitation with Stations (CHIRPS) and the Tropical Rainfall Measuring Mission (TRMM) Multi-Satellite Precipitation Analysis (TMPA), outperform those run with MERRA-Land and MERRA-2 precipitation. The results presented in this paper would suggest that the Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System incorporate CLSMF2.5 and HyMAP routing scheme to better represent the water balance in this region.

Evaluating ESA CCI soil moisture in East Africa.

To assess growing season conditions where ground based observations are limited or unavailable, food security and agricultural drought monitoring analysts rely on publicly available remotely sensed rainfall and vegetation greenness. There are also remotely sensed soil moisture observations from missions like the European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) and NASA's Soil Moisture Active Passive (SMAP), however these time series are still too short to conduct studies that demonstrate the utility of these data for operational applications, or to provide historical context for extreme wet or dry events. To promote the use of remotely sensed soil moisture in agricultural drought and food security monitoring, we use East Africa as a case study to evaluate the quality of a 30+ year time series of merged active-passive microwave soil moisture from the ESA Climate Change Initiative (CCI-SM). Compared to the Normalized Difference Vegetation index (NDVI) and modeled soil moisture products, we found substantial spatial and temporal gaps in the early part of the CCI-SM record, with adequate data coverage beginning in 1992. From this point forward, growing season CCI-SM anomalies were well correlated (R>0.5) with modeled, seasonal soil moisture, and in some regions, NDVI. We use correlation analysis and qualitative comparisons at seasonal time scales to show that remotely sensed soil moisture can add information to a convergence of evidence framework that traditionally relies on rainfall and NDVI in moderately vegetated regions.

Understanding uncertainty in temperature effects on vector-borne disease: a Bayesian approach.

Extrinsic environmental factors influence the distribution and population dynamics of many organisms, including insects that are of concern for human health and agriculture. This is particularly true for vector-borne infectious diseases like malaria, which is a major source of morbidity and mortality in humans. Understanding the mechanistic links between environment and population processes for these diseases is key to predicting the consequences of climate change on transmission and for developing effective interventions. An important measure of the intensity of disease transmission is the reproductive number R0. However, understanding the mechanisms linking R0 and temperature, an environmental factor driving disease risk, can be challenging because the data available for parameterization are often poor. To address this, we show how a Bayesian approach can help identify critical uncertainties in components of R0 and how this uncertainty is propagated into the estimate of R0. Most notably, we find that different parameters dominate the uncertainty at different temperature regimes: bite rate from 15 degrees C to 25 degrees C; fecundity across all temperatures, but especially approximately 25-32 degrees C; mortality from 20 degrees C to 30 degrees C; parasite development rate at degrees 15-16 degrees C and again at approximately 33-35 degrees C. Focusing empirical studies on these parameters and corresponding temperature ranges would be the most efficient way to improve estimates of R0. While we focus on malaria, our methods apply to improving process-based models more generally, including epidemiological, physiological niche, and species distribution models.

Ultrasound-guided subcostal transversus abdominis plane infiltration with liposomal bupivacaine for patients undergoing robotic-assisted hysterectomy: a retrospective study.

OBJECTIVE: We sought to determine the effect of a subcostal transversus abdominis plane (TAP) block with liposomal bupivacaine on postoperative maximal pain score and length of hospital stay among women undergoing robotic-assisted hysterectomy. METHODS: This was a retrospective study comparing patients before and after consistent implementation of TAP blocks with liposomal bupivacaine during robotic-assisted hysterectomies at a single academic institution. Analysis compared patient demographic and operative characteristics by TAP block use, along with outcomes of interest, including postoperative pain and length of hospital stay. RESULTS: There was a statistically significant decrease in maximal numerical rating scale pain scores, presence of nausea and vomiting, and length of hospital stay in those who had a TAP block with liposomal bupivacaine compared with those who did not receive a TAP block. These differences remained even after adjustment for potential confounders. CONCLUSIONS: In this retrospective study, liposomal bupivacaine used in a TAP block was a useful method to provide postoperative pain control in patients undergoing robotic-assisted hysterectomy and was associated with lower postoperative maximal pain scores and length of hospital stay.

Preseason maize and wheat yield forecasts for early warning of crop failure.

Provided the considerable logistical challenges of anticipatory action and disaster response programs, there is a need for early warning of crop failures at lead times of six to twelve months. But crop yield forecasts at these lead times are virtually nonexistent. By leveraging recent advances in climate forecasting, we demonstrate that global preseason crop yield forecasts are not only possible but are skillful over considerable portions of cropland. Globally, maize and wheat forecasts are skillful at lead times of up to a year ahead of harvest for 15% and 30% of harvested areas, respectively. Forecasts are most skillful in Southeast Africa and Southeast Asia for maize and parts of South and Central Asia, Australia, and Southeast South America for wheat. Wheat forecasts, furthermore, remain skillful at lead times of over 18 months ahead of harvest in some locations. Our results demonstrate that the potential for preseason crop yield forecasts is greater than previously appreciated.

Optimal temperature for malaria transmission is dramatically lower than previously predicted.

The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.

A global long-term daily reanalysis of reference evapotranspiration for drought and food-security monitoring.

NOAA has developed a global reference evapotranspiration (ET0) reanalysis using the UN Food and Agriculture Organization formulation (FAO-56) of the Penman-Monteith equation forced by MERRA phase 2 (MERRA2) meteorological and radiative drivers. The NOAA ET0 reanalysis is provided daily from January 1, 1980 to the near-present at a resolution of 0.5° latitude × 0.625° longitude. The reanalysis is verified against station data across southern Africa, a region presenting both significant challenges regarding hydroclimatic variability and observational quantity and quality and significant potential benefits to food-insecure populations. These data are generated from observations from the Southern African Science Service Centre for Climate Change and Adaptive Land Management (SASSCAL) network. We further verified globally against spatially distributed ET0 derived from two reanalyses-the Global Data Assimilation System (GDAS) and Princeton Global Forcing (PGF)-and these verifications produced similar results, yet demonstrated wide regional and seasonal differences. We also present cases that verify the operational applicability of the reanalysis in long-established drought, famine, crop- and pastoral-stress metrics, and in predictability assessments of drought forecasts.

Estimating groundwater use and demand in arid Kenya through assimilation of satellite data and in-situ sensors with machine learning toward drought early action.

Groundwater is an important source of water for people, livestock, and agriculture during drought in the Horn of Africa. In this work, areas of high groundwater use and demand in drought-prone Kenya were identified and forecasted prior to the dry season. Estimates of groundwater use were extended from a sentinel network of 69 in-situ sensored mechanical boreholes to the region with satellite data and a machine learning model. The sensors contributed 756 site-month observations from June 2017 to September 2021 for model building and validation at a density of approximately one sensor per 3700 km2. An ensemble of 19 parameterized algorithms was informed by features including satellite-derived precipitation, surface water availability, vegetation indices, hydrologic land surface modeling, and site characteristics to dichotomize high groundwater pump utilization. Three operational definitions of high demand on groundwater infrastructure were considered: 1) mechanical runtime of pumps greater than a quarter of a day (6+ hr) and daily per capita volume extractions indicative of 2) domestic water needs (35+ L), and 3) intermediate needs including livestock (75+ L). Gridded interpolation of localized groundwater use and demand was provided from 2017 to 2020 and forecasted for the 2021 dry season, June-September 2021. Cross-validated skill for contemporary estimates of daily pump runtime and daily volume extraction to meet domestic and intermediate water needs was 68%, 69%, and 75%, respectively. Forecasts were externally validated with an accuracy of at least 56%, 70%, or 72% for each groundwater use definition. The groundwater maps are accessible to stakeholders including the Kenya National Drought Management Authority (NDMA) and the Famine Early Warning Systems Network (FEWS NET). These maps represent the first operational spatially-explicit sub-seasonal to seasonal (S2S) estimates of groundwater use and demand in the literature. Knowledge of historical and forecasted groundwater use is anticipated to improve decision-making and resource allocation for a range of early warning early action applications.

Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells.

Foreign body-type multinucleated giant cells (FBGC), formed by macrophage fusion, are a prominent cell type on implanted biomaterials, although the roles they play at these and other sites of chronic inflammation are not understood. Why lymphocytes are present in this scenario and the effects of fusing macrophages/FBGC on subsequent lymphocyte responses are also unclear. To address the physiological significance of FBGC in this regard, we employed our in vitro system of interleukin (IL)-4-induced human monocyte-derived macrophage fusion/FBGC formation. Initially, we pursued the identities of lymphocyte co-stimulatory molecules on fusing macrophages/FBGC. In addition, we further compared the FBGC phenotype to that currently associated with osteoclasts and dendritic cells using recognized markers. Immunoblotting of cell lysates and immunochemistry of macrophages/FBGC in situ, revealed that IL-4-induced macrophages/FBGC strongly express HLA-DR, CD98, B7-2 (CD86), and B7-H1 (PD-L1), but not B7-1 (CD80) or B7-H2 (B7RP-1). Furthermore, molecules currently recognized to be expressed on osteoclasts (calcitonin receptor, tartrate-resistant acid phosphatase, RANK) or dendritic cells (CD1a, CD40, CD83, CD95/fas) are undetectable. In contrast, fusing macrophages/FBGC strongly express the macrophage markers αX integrin (CD11c), CD68, and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), whereas CD14 is completely down-modulated with IL-4-induced macrophage fusion. These novel data demonstrate that IL-4-induction of macrophage multinucleation/FBGC formation features the acquisition of a CD14-negative phenotypic profile which is distinguishable from that of dendritic cells and osteoclasts, yet potentially exhibits multiple capacities for lymphocyte interactions with resultant lymphocyte down-modulation.

Macrophage fusion and multinucleated giant cells of inflammation.

Macrophages undergo fusion with other macrophages to form the hallmark multinucleated giant cells of chronic inflammation. However, neither the existence of distinct morphological types of giant cells, the signaling pathways that induce their formation, the molecular mechanism(s) of macrophage fusion, nor the significance of macrophage multinucleation at chronic inflammatory sites are well understood. Our efforts have been focused on these unknowns, particularly as they relate to the foreign body-type giant cells that form on implanted biomaterials and biomedical devices. We have pursued the discoveries of human macrophage fusion factors (interleukin-4, interleukin-13, α-tocopherol) with emphasis on foreign body giant cells, and identified adhesion receptors and signaling intermediates, as well as an adhesion protein substrate (vitronectin) that supports macrophage fusion. Studies on the molecular mechanism of macrophage fusion have revealed it to be a mannose receptor-mediated phagocytic process with participation of the endoplasmic reticulum. Further phenotypic and functional investigations will foster new perspectives on these remarkable multinucleated cells and their physiological significances in multiple inflammatory processes.

Hydropower and sustainability: resilience and vulnerability in China's powersheds.

Large dams represent a whole complex of social, economic and ecological processes, perhaps more than any other large infrastructure project. Today, countries with rapidly developing economies are constructing new dams to provide energy and flood control to growing populations in riparian and distant urban communities. If the system is lacking institutional capacity to absorb these physical and institutional changes there is potential for conflict, thereby threatening human security. In this paper, we propose analyzing sustainability (political, socioeconomic, and ecological) in terms of resilience versus vulnerability, framed within the spatial abstraction of a powershed. The powershed framework facilitates multi-scalar and transboundary analysis while remaining focused on the questions of resilience and vulnerability relating to hydropower dams. Focusing on examples from China, this paper describes the complex nature of dams using the sustainability and powershed frameworks. We then analyze the roles of institutions in China to understand the relationships between power, human security and the socio-ecological system. To inform the study of conflicts over dams China is a particularly useful case study because we can examine what happens at the international, national and local scales. The powershed perspective allows us to examine resilience and vulnerability across political boundaries from a dynamic, process-defined analytical scale while remaining focused on a host of questions relating to hydro-development that invoke drivers and impacts on national and sub-national scales. The ability to disaggregate the affects of hydropower dam construction from political boundaries allows for a deeper analysis of resilience and vulnerability. From our analysis we find that reforms in China's hydropower sector since 1996 have been motivated by the need to create stability at the national scale rather than resilient solutions to China's growing demand for energy and water resource control at the local and international scales. Some measures that improved economic development through the market economy and a combination of dam construction and institutional reform may indeed improve hydro-political resilience at a single scale. However, if China does address large-scale hydropower construction's potential to create multi-scale geopolitical tensions, they may be vulnerable to conflict - though not necessarily violent - in domestic and international political arenas. We conclude with a look toward a resilient basin institution for the Nu/Salween River, the site of a proposed large-scale hydropower development effort in China and Myanmar.

Earth observations and integrative models in support of food and water security.

Global food production depends upon many factors that Earth observing satellites routinely measure about water, energy, weather, and ecosystems. Increasingly sophisticated, publicly-available satellite data products can improve efficiencies in resource management and provide earlier indication of environmental disruption. Satellite remote sensing provides a consistent, long-term record that can be used effectively to detect large-scale features over time, such as a developing drought. Accuracy and capabilities have increased along with the range of Earth observations and derived products that can support food security decisions with actionable information. This paper highlights major capabilities facilitated by satellite observations and physical models that have been developed and validated using remotely-sensed observations. Although we primarily focus on variables relevant to agriculture, we also include a brief description of the growing use of Earth observations in support of aquaculture and fisheries.

Matrix metalloproteinases and their inhibitors in the foreign body reaction on biomaterials.

Matrix metalloproteinases (MMPs) can degrade structural components within the extracellular matrix and at the cellular surface producing changes in cellular behavior (i.e., adhesion and migration) and subsequent pathological responses (i.e., the foreign body reaction and wound healing). We continue to study the foreign body reaction that occurs following biomaterial implantation by investigating secretory responses of biomaterial-adherent macrophages and foreign body giant cells (FBGCs) as directed by material surface chemistry and further this research by determining whether secreted MMPs play a role in macrophage adhesion and fusion. We have identified numerous MMPs and their tissue inhibitors (TIMPs) in in vitro cell-culture supernatants using antibody arrays and quantified select MMP/TIMPs with ELISAs. MMP-9 concentrations were significantly greater than both TIMP-1 and TIMP-2 on all materials. The ratios of MMP-9/TIMP-1 and MMP-9/TIMP-2 increased with time because of an increase in MMP-9 concentrations over time, while the TIMP concentrations remained constant. Total MMP-9 concentrations in the supernatants were comparable on all materials at each timepoint, while TIMP-1 and TIMP-2 concentrations tended to be greater on hydrophilic/anionic surfaces. Analysis of the MMP/TIMP quantities produced per cell revealed that the hydrophilic/neutral surfaces, which inhibited macrophage adhesion, activated the adherent macrophages/FBGCs to produce a greater quantity of MMP-9, TIMP-1, and TIMP-2 per cell. Pharmacological inhibition of MMP-1,-8,-13, and -18 reduced macrophage fusion without affecting adhesion, while inhibitors of MMP-2,-3,-9, and -12 did not affect adhesion or fusion. These findings demonstrate that material surface chemistry does modulate macrophage/FBGC-derived MMP/TIMP secretion and implicates MMP involvement in macrophage fusion.

Integrating the social, hydrological and ecological dimensions of freshwater health: The Freshwater Health Index.

Degradation of freshwater ecosystems and the services they provide is a primary cause of increasing water insecurity, raising the need for integrated solutions to freshwater management. While methods for characterizing the multi-faceted challenges of managing freshwater ecosystems abound, they tend to emphasize either social or ecological dimensions and fall short of being truly integrative. This paper suggests that management for sustainability of freshwater systems needs to consider the linkages between human water uses, freshwater ecosystems and governance. We present a conceptualization of freshwater resources as part of an integrated social-ecological system and propose a set of corresponding indicators to monitor freshwater ecosystem health and to highlight priorities for management. We demonstrate an application of this new framework -the Freshwater Health Index (FHI) - in the Dongjiang River Basin in southern China, where stakeholders are addressing multiple and conflicting freshwater demands. By combining empirical and modeled datasets with surveys to gauge stakeholders' preferences and elicit expert information about governance mechanisms, the FHI helps stakeholders understand the status of freshwater ecosystems in their basin, how ecosystems are being manipulated to enhance or decrease water-related services, and how well the existing water resource management regime is equipped to govern these dynamics over time. This framework helps to operationalize a truly integrated approach to water resource management by recognizing the interplay between governance, stakeholders, freshwater ecosystems and the services they provide.

alpha subunit partners to beta1 and beta2 integrins during IL-4-induced foreign body giant cell formation.

As beta1 and beta2 integrins were previously found to mediate adhesion during IL-4-induced foreign body giant cell (FBGC) formation, we pursued the identities of the alpha integrin partners of these adhesion receptors using our in vitro system of human monocyte-derived macrophage fusion. Immunoprecipitation with beta1 and immunoblotting reveal the presence of alpha5 and alphaV, as well as alpha2 and alpha3. alphaM and alphaX immunoprecipitate with beta2 but not with beta1. Immunocytochemistry coupled with confocal microscopy indicates that alpha5 and alphaX are poorly expressed on day 0. However, following the induction of fusion by IL-4 on day 3, they are each readily detectable in fusing macrophages/FBGC on day 7. In contrast, alphaM and alphaV are present throughout the culture period, with very strong alphaM expression on day 7. We also demonstrate expression and colocalization of alpha3, alpha5, or alphaV with beta1 on fusing macrophages/FBGC at this time point as well as strong colocalization of alphaM and alphaX with beta2 in FBGC and at fusion interfaces. Therefore, IL-4-induced FBGC are characterized by the expression of alphaMbeta2, alphaXbeta2, alpha5beta1, alphaVbeta1, alpha2beta1, and alpha3beta1, which indicates potential interactions with fragments of complement C3, fibrin(ogen), fibronectin, Factor X, and vitronectin, and possibly with certain collagens, laminin, and thrombospondin at sites of biomaterial implantation.

A land data assimilation system for sub-Saharan Africa food and water security applications.

Seasonal agricultural drought monitoring systems, which rely on satellite remote sensing and land surface models (LSMs), are important for disaster risk reduction and famine early warning. These systems require the best available weather inputs, as well as a long-term historical record to contextualize current observations. This article introduces the Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (FLDAS), a custom instance of the NASA Land Information System (LIS) framework. The FLDAS is routinely used to produce multi-model and multi-forcing estimates of hydro-climate states and fluxes over semi-arid, food insecure regions of Africa. These modeled data and derived products, like soil moisture percentiles and water availability, were designed and are currently used to complement FEWS NET's operational remotely sensed rainfall, evapotranspiration, and vegetation observations. The 30+ years of monthly outputs from the FLDAS simulations are publicly available from the NASA Goddard Earth Science Data and Information Services Center (GES DISC) and recommended for use in hydroclimate studies, early warning applications, and by agro-meteorological scientists in Eastern, Southern, and Western Africa.

Phenotypic expression in human monocyte-derived interleukin-4-induced foreign body giant cells and macrophages in vitro: dependence on material surface properties.

The effects of different material surfaces on phenotypic expression in macrophages and foreign body giant cells (FBGC) were addressed using our in vitro system of interleukin (IL)-4-induced macrophage fusion and FBGC formation. Arginine-glycine-aspartate (RGD)-, vitronectin (VN)-, and chitosan (CH)-adsorbed cell culture polystyrene, carboxylated (C, negatively charged) polystyrene, and unmodified (PS, non-cell culture treated) polystyrene were compared for their abilities to support monocyte/macrophage adhesion and IL-4-induced macrophage fusion. Pooled whole cell lysates from four different donors were evaluated by immunoblotting for expression of selected components in monocytes, macrophages, and FBGC. In addition to RGD and VN as previously shown, we find that CH supports macrophage adhesion and FBGC formation, whereas C or PS support macrophage adhesion but do not permit macrophage fusion under otherwise identical conditions of IL-4 stimulation. Likewise, components related to macrophage fusion (CD206, CD98, CD147, CD13) are strongly expressed on RGD-, VN-, and CH-adsorbed surfaces but are greatly diminished or not detected on C or PS. Importantly, material surfaces also influence the FBGC phenotype itself, as demonstrated by strong differences in patterns of expression of HLA-DR, B7-2, B7-H1, and toll-like receptor (TLR)-2 on RGD, VN, and CH despite morphologic similarities between FBGC on these surfaces. Likewise, we observe differences in the expression of B7-2, α2-macroglobulin, TLR-2, and fascin-1 between mononuclear macrophages on C and PS. Collectively, these findings reveal the extent to which material surface chemistry influences macrophage/FBGC phenotype beyond evident morphological similarities or differences and identify CH as an FBGC-supportive substrate.

Mapping Physiological Suitability Limits for Malaria in Africa Under Climate Change.

We mapped current and future temperature suitability for malaria transmission in Africa using a published model that incorporates nonlinear physiological responses to temperature of the mosquito vector Anopheles gambiae and the malaria parasite Plasmodium falciparum. We found that a larger area of Africa currently experiences the ideal temperature for transmission than previously supposed. Under future climate projections, we predicted a modest increase in the overall area suitable for malaria transmission, but a net decrease in the most suitable area. Combined with human population density projections, our maps suggest that areas with temperatures suitable for year-round, highest-risk transmission will shift from coastal West Africa to the Albertine Rift between the Democratic Republic of Congo and Uganda, whereas areas with seasonal transmission suitability will shift toward sub-Saharan coastal areas. Mapping temperature suitability places important bounds on malaria transmissibility and, along with local level demographic, socioeconomic, and ecological factors, can indicate where resources may be best spent on malaria control.

In vivo quantitative and qualitative assessment of foreign body giant cell formation on biomaterials in mice deficient in natural killer lymphocyte subsets, mast cells, or the interleukin-4 receptorα and in severe combined immunodeficient mice.

In previous studies that explored the influence of cytokines on foreign body giant cell (FBGC) formation, we focused on interleukin (IL)-4 and IL-13, each of which was discovered to induce macrophage fusion leading to FBGC formation in vitro. Two correlative in vivo studies also confirmed that IL-4 plays a role in FBGC formation on implanted biomaterials, but that T lymphocytes are not the source of IL-4 or other cytokines that support this process. The present study focused on identification of the cellular source of macrophage fusion-inducing cytokines, including natural killer (NK) or NKT lymphocytes and mast cells using mouse models genetically deficient in each of these cell types, as well as IL-4 receptor alpha(IL-4Rα)-deficient and severe combined immunodeficient (SCID) mice. Polyetherurethane (PEU) and polyethylene terephthalate (PET) polymers were subcutaneously implanted and retrieved after 14, 21, or 28 days. FBGC formation was evaluated using quantitative and qualitative data from retrieved polymer surfaces. Both types of data indicate that, compared to normal control mice, neither NK or NKT lymphocytes nor mast cells are required for FBGC formation. Furthermore, FBGC formation on biomaterials can proceed in IL-4Rα-deficient and in SCID mice. Similar conclusions were made regarding FBGC formation on both PEU and PET biomaterials. These data suggest that other sources of IL-4/IL-13 and/or additional macrophage fusion-inducing cytokines can mediate FBGC formation on implanted biomaterials, or that, in the absence of normal primary pathways, FBGC formation is nevertheless supported by redundant innate mechanisms.