Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

BACKGROUND: Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. METHODS: This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. RESULTS: Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. CONCLUSION: In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

Quantifying Inferior Vena Cava Compliance and Distensibility in an In Vivo Ovine Model Using 3D Angiography.

Synthetic vascular grafts overcome some challenges of allografts, autografts, and xenografts but are often more rigid and less compliant than the native vessel into which they are implanted. Compliance matching with the native vessel is emerging as a key property for graft success. The current gold standard for assessing vessel compliance involves the vessel's excision and ex vivo biaxial mechanical testing. We developed an in vivo method to assess venous compliance and distensibility that better reflects natural physiology and takes into consideration the impact of a pressure change caused by flowing blood and by any morphologic changes present. This method is designed as a survival procedure, facilitating longitudinal studies while potentially reducing the need for animal use. Our method involves injecting a 20 mL/kg saline bolus into the venous vasculature, followed by the acquisition of pre and post bolus 3D angiograms to observe alterations induced by the bolus, concurrently with intravascular pressure measurements in target regions. We are then able to measure the circumference and the cross-sectional area of the vessel pre and post bolus. With these data and the intravascular pressure, we are able to calculate the compliance and distensibility with specific equations. This method was used to compare the inferior vena cava's compliance and distensibility in native unoperated sheep to the conduit of sheep implanted with a long-term expanded polytetrafluorethylene (PTFE) graft. The native vessel was found to be more compliant and distensible than the PTFE graft at all measured locations. We conclude that this method safely provides in vivo measurements of vein compliance and distensibility.

Impact of pneumococcal conjugate vaccine 13 introduction on severe lower respiratory tract infections associated with respiratory syncytial virus or influenza virus in hospitalized children in Ulaanbaatar, Mongolia.

Objectives: Limited data indicate a beneficial effect of pneumococcal conjugate vaccines (PCVs) on respiratory syncytial virus (RSV) and influenza infections in young children. We evaluated the impact of 13-valent PCV (PCV13) introduction on the incidence of severe lower respiratory tract infections (LRTIs) associated with RSV or influenza in hospitalized children. Methods: Our study was restricted to children aged <2 years with arterial oxygen saturation <93% and children with radiologically confirmed pneumonia nested in a pneumonia surveillance project in four districts of Ulaanbaatar city, Mongolia. We tested nasopharyngeal swabs collected on admission for RSV and influenza using quantitative reverse transcription-polymerase chain reaction. The impact of PCV13 on the incidence of LRTI outcomes associated with RSV or with influenza for the period April 2015-March 2020 was estimated. Incidence rate ratios comparing pre- and post-vaccine periods were estimated for each outcome for each district using negative binomial models and for all districts combined with a mixed-effects negative binomial model. Adjusted models accounted for seasonality. Sensitivity analyses were conducted to assess the robustness of our findings. Results: Among 5577 tested cases, the adjusted incidence rate ratios showed a trend toward a reduction in RSV-associated outcomes: all LRTIs (0.77, 95% confidence interval [CI] 0.44-1.36), severe LRTIs (0.88, 95% CI 0.48-1.62), very severe LRTIs (0.76, 95% CI 0.42-1.38), and radiologically confirmed pneumonia (0.66, 95% CI 0.32-1.38) but inconsistent trends in outcomes associated with influenza. Conclusions: No significant reductions were observed in any outcomes associated with RSV and influenza after PCV introduction.

Effect of Pneumococcal Conjugate Vaccine on Pneumonia Incidence Rates among Children 2-59 Months of Age, Mongolia, 2015-2021.

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.

Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis.

Background: Few studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016. Methods: We conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015-February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings. Findings: The average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62.81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisation in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden. Interpretation: We did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults. Funding: Pfizer clinical research collaboration agreement (contract number: WI236621).

Acaricidal Toxicity of Four Essential Oils, Their Predominant Constituents, Their Mixtures against Varroa Mite, and Their Selectivity to Honey Bees (Apis cerana and A. mellifera).

The honey bee (Apis mellifera) faces a significant threat from Varroa destructor, causing the losses of millions of colonies worldwide. While synthetic acaricides are widely used to control Varroa infestations, excessive application has led to resistant strains and poses side effects on the host. Consequently, there is an urgent need for a new acaricide that is both effective and affordable, yet safe to use on bees. One potential source of these acaricides is essential oils (EOs) and their constituents. This study evaluated the acaricidal properties of four essential oils (Eucalyptus globulus, Rosemary officinalis, Trachyspermum ammi (Ethiopian and Indian varieties), their constituents and mixture of constituents against V. destructor through the complete exposure method. Our finding showed that a 1:1 mixture of thymol and carvacrol (4 h-LC50 = 42 µg/mL), thymol (4 h-LC50 = 71 µg/mL), and T. ammi oil (4 h-LC50 = 81-98 µg/mL) were the most toxic test samples against V. destructor. Honey bee behavior and selectivity were also assessed with one additional EO Thymus schimperi, indicating that T. schimperi, T. ammi, and their components were selective and did not affect the learning and memory of bees. In conclusion, the thymol and carvacrol (1:1) mixture was shown to be a promising replacement for synthetic acaricides, being three times more toxic than a commercial acaricide, fluvalinate (4 h-LC50 = 143 µg/mL).

Recent Tissue Engineering Approaches to Mimicking the Extracellular Matrix Structure for Skin Regeneration.

Inducing tissue regeneration in many skin defects, such as large traumatic wounds, burns, other physicochemical wounds, bedsores, and chronic diabetic ulcers, has become an important clinical issue in recent years. Cultured cell sheets and scaffolds containing growth factors are already in use but have yet to restore normal skin tissue structure and function. Many tissue engineering materials that focus on the regeneration process of living tissues have been developed for the more versatile and rapid initiation of treatment. Since the discovery that cells recognize the chemical-physical properties of their surrounding environment, there has been a great deal of work on mimicking the composition of the extracellular matrix (ECM) and its three-dimensional network structure. Approaches have used ECM constituent proteins as well as morphological processing methods, such as fiber sheets, sponges, and meshes. This review summarizes material design strategies in tissue engineering fields, ranging from the morphology of existing dressings and ECM structures to cellular-level microstructure mimicry, and explores directions for future approaches to precision skin tissue regeneration.

Recent Developments in Biopolymer-Based Hydrogels for Tissue Engineering Applications.

Hydrogels are being investigated for their application in inducing the regeneration of various tissues, and suitable conditions for each tissue are becoming more apparent. Conditions such as the mechanical properties, degradation period, degradation mechanism, and cell affinity can be tailored by changing the molecular structure, especially in the case of polymers. Furthermore, many high-functional hydrogels with drug delivery systems (DDSs), in which drugs or bioactive substances are contained in controlled hydrogels, have been reported. This review focuses on the molecular design and function of biopolymer-based hydrogels and introduces recent developments in functional hydrogels for clinical applications.

The Application of Porous Scaffolds for Cardiovascular Tissues.

As the number of arteriosclerotic diseases continues to increase, much improvement is still needed with treatments for cardiovascular diseases. This is mainly due to the limitations of currently existing treatment options, including the limited number of donor organs available or the long-term durability of the artificial organs. Therefore, tissue engineering has attracted significant attention as a tissue regeneration therapy in this area. Porous scaffolds are one of the effective methods for tissue engineering. However, it could be better, and its effectiveness varies depending on the tissue application. This paper will address the challenges presented by various materials and their combinations. We will also describe some of the latest methods for tissue engineering.

Epidemiology of pneumonia in hospitalized adults ≥18 years old in four districts of Ulaanbaatar, Mongolia, 2015-2019.

Background: Community-acquired pneumonia is a leading cause of morbidity and mortality among children and adults worldwide. Adult pneumonia surveillance remains limited in many low- and middle-income settings, resulting in the disease burden being largely unknown. Methods: A retrospective cohort study was conducted by reviewing medical charts for respiratory admissions at four district hospitals in Ulaanbaatar during January 2015-February 2019. Characteristics of community-acquired pneumonia cases were summarized by disease severity and age. To explore factors associated with severe pneumonia, we ran univariable and age-adjusted logistic regression models. Incidence rates were calculated using population denominators. Results: In total, 4290 respiratory admissions met the case definition for clinical pneumonia, including 430 admissions of severe pneumonia. The highest proportion of severe pneumonia admissions occurred in adults >65 years (37.4%). After adjusting for age, there were increased odds of severe pneumonia in males (adjusted odds ratio [aOR]: 1.63; 95% confidence interval [CI]: 1.33-2.00) and those with ≥1 underlying medical condition (aOR: 1.46; 95% CI: 1.14-1.87). The incidence of hospitalized pneumonia in adults ≥18 years increased from 13.49 (95% CI: 12.58-14.44) in 2015 to 17.65 (95% CI: 16.63-18.71) in 2018 per 10,000 population. The incidence of severe pneumonia was highest in adults >65 years, ranging from 9.29 (95% CI: 6.17-13.43) in 2015 to 12.69 (95% CI: 9.22-17.04) in 2018 per 10,000 population. Interpretations: Vaccination and other strategies to reduce the risk of pneumonia, particularly among older adults and those with underlying medical conditions, should be prioritized. Funding: Pfizer clinical research collaboration agreement (contract number: WI236621).

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure.

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Advances in Cardiac Tissue Engineering.

Tissue engineering has paved the way for the development of artificial human cardiac muscle patches (hCMPs) and cardiac tissue analogs, especially for treating Myocardial infarction (MI), often by increasing its regenerative abilities. Low engraftment rates, insufficient clinical application scalability, and the creation of a functional vascular system remain obstacles to hCMP implementation in clinical settings. This paper will address some of these challenges, present a broad variety of heart cell types and sources that can be applied to hCMP biomanufacturing, and describe some new innovative methods for engineering such treatments. It is also important to note the injection/transplantation of cells in cardiac tissue engineering.

Clinical Application for Tissue Engineering Focused on Materials.

Cardiovascular-related medical conditions remain a significant cause of death worldwide despite the advent of tissue engineering research more than half a century ago. Although autologous tissue is still the preferred treatment, donor tissue is limited, and there remains a need for tissue-engineered vascular grafts (TEVGs). The production of extensive vascular tissue (>1 cm3) in vitro meets the clinical needs of tissue grafts and biological research applications. The use of TEVGs in human patients remains limited due to issues related to thrombogenesis and stenosis. In addition to the advancement of simple manufacturing methods, the shift of attention to the combination of synthetic polymers and bio-derived materials and cell sources has enabled synergistic combinations of vascular tissue development. This review details the selection of biomaterials, cell sources and relevant clinical trials related to large diameter vascular grafts. Finally, we will discuss the remaining challenges in the tissue engineering field resulting from complex requirements by covering both basic and clinical research from the perspective of material design.

Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth.

Background: Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity. Methods: Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models. Results: Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid-structure interaction simulations providing detailed hemodynamic and wall stress information. Conclusions: These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease.

Current status of developing tissue engineering vascular technologies.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in western countries. Although surgical outcomes for CVD are dramatically improving with the development of surgical techniques, medications, and perioperative management strategies, adverse postoperative events related to the use of artificial prosthetic materials are still problematic. Moreover, in pediatric patients, using these artificial materials make future re-intervention inevitable due to their lack of growth potential. AREAS COVERED: This review focuses on the most current tissue-engineering (TE) technologies to treat cardiovascular diseases and discusses their limitations through reports ranging from animal studies to clinical trials. EXPERT OPINION: Tissue-engineered structures, derived from a patient's own autologous cells/tissues and biodegradable polymer scaffolds, can provide mechanical function similar to non-diseased tissue. However, unlike prosthetic materials, tissue-engineered structures are hypothetically more biocompatible and provide growth potential, saving patients from additional or repetitive interventions. While there are many methods being investigated to develop TE technologies in the hopes of finding better options to tackle CVD, most of these approaches are not ready for clinical use or trials. However, tissue engineering has great promise to potentially provide better treatment options to vastly improve cardiovascular surgical outcomes.

Evaluation of the impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia in Ulaanbaatar, Mongolia: study protocol for an observational study.

BACKGROUND: Community-acquired pneumonia is an important cause of morbidity and mortality in adults. Approximately one-third of pneumonia cases can be attributed to the pneumococcus. Pneumococcal conjugate vaccines (PCVs) protect against colonisation with vaccine-type serotypes. The resulting decrease in transmission of vaccine serotypes leads to large indirect effects. There are limited data from developing countries demonstrating the impact of childhood PCV immunisation on adult pneumonia. There are also insufficient data available on the burden and severity of all-cause pneumonia and respiratory syncytial virus (RSV) in adults from low resource countries. There is currently no recommendation for adult pneumococcal vaccination with either pneumococcal polysaccharide vaccine or PCVs in Mongolia. We describe the protocol developed to evaluate the association between childhood 13-valent PCV (PCV13) vaccination and trends in adult pneumonia. METHODS: PCV13 was introduced into the routine childhood immunisation schedule in Mongolia in a phased manner from 2016. In March 2019 we initiated active hospital-based surveillance for adult pneumonia, with the primary objective of evaluating trends in severe hospitalised clinical pneumonia incidence in adults 18 years and older in four districts of Ulaanbaatar. Secondary objectives include measuring the association between PCV13 introduction and trends in all clinically-defined pneumonia, radiologically-confirmed pneumonia, nasopharyngeal carriage of S. pneumoniae and pneumonia associated with RSV or influenza. Clinical questionnaires, nasopharyngeal swabs, urine samples and chest radiographs were collected from enrolled patients. Retrospective administrative and clinical data were collected for all respiratory disease-related admissions from January 2015 to February 2019. DISCUSSION: Establishing a robust adult surveillance system may be an important component of monitoring the indirect impact of PCVs within a country. Monitoring indirect impact of childhood PCV13 vaccination on adult pneumonia provides additional data on the full public health impact of the vaccine, which has implications for vaccine efficiency and cost-effectiveness. Adult surveillance in Mongolia will contribute to the limited evidence available on the burden of pneumococcal pneumonia among adults in low- and middle-income countries, particularly in the Asia-Pacific region. In addition, it is one of the few examples of implementing prospective, population-based pneumonia surveillance to evaluate the indirect impact of PCVs in a resource-limited setting.

Direct and indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with pneumonia from formal and informal settlements in Mongolia: an observational study.

BACKGROUND: Within Ulaanbaatar, Mongolia, risk factors for pneumonia are concentrated among children living in informal settlements comprised of temporary shelters (gers). We used pneumococcal carriage surveillance among children from formal and informal settlements hospitalised with pneumonia to evaluate the direct and indirect effects of 13-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) pneumococcal carriage following a phased introduction of PCV13. METHODS: We enrolled and collected nasopharyngeal swabs from children 2-59 months of age presenting to hospital. Pneumococci were detected using lytA qPCR and serotyped using microarray on a random monthly selection of swabs between November 2015 and March 2019 from two districts in Ulaanbaatar. PCV13 status was determined using written records. We quantified the associations between individual PCV13 status (direct effects) and district-level PCV13 coverage (indirect effects) and VT carriage using generalised estimating equations and explored interactions by settlement type. FINDINGS: A total of 1 292 swabs from 6 046 participants were tested for pneumococci. Receipt of PCV13 and increasing PCV13 coverage independently reduced the risk of VT carriage. For each percent increase in PCV13 coverage, the adjusted odds of VT carriage decreased by 1•0% (OR 95% CI 0•983-0•996; p=0•001), with a predicted decrease in VT carriage rate from 29•1% to 13•1% as coverage reached 100%. There was a trend towards a slower decline within informal settlements (p=0•100). Adjusted PCV13 vaccine effectiveness against VT carriage was 39•1% (95% CI 11•4-58•1%, p=0•009). INTERPRETATION: Substantial indirect effects were observed following PCV13 introduction, including among children living within informal settlements. FUNDING: Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance.

A Dynamic 6,000-Year Genetic History of Eurasia's Eastern Steppe.

The Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the region's population history. Here, we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

The effect of pore diameter on neo-tissue formation in electrospun biodegradable tissue-engineered arterial grafts in a large animal model.

To date, there has been little investigation of biodegradable tissue engineered arterial grafts (TEAG) using clinically relevant large animal models. The purpose of this study is to explore how pore size of electrospun scaffolds can be used to balance neoarterial tissue formation with graft structural integrity under arterial environmental conditions throughout the remodeling process. TEAGs were created with an outer poly-ε-caprolactone (PCL) electrospun layer and an inner sponge layer composed of heparin conjugated 50:50 poly (l-lactide-co-ε-caprolactone) copolymer (PLCL). Outer electrospun layers were created with four different pore diameters (4, 7, 10, and 15 µm). Fourteen adult female sheep underwent bilateral carotid artery interposition grafting (n = 3-4 /group). Our heparin-eluting TEAG was implanted on one side (n = 14) and ePTFE graft (n = 3) or non-heparin-eluting TEAG (n = 5) on the other side. Twelve of the fourteen animals survived to the designated endpoint at 8 weeks, and one animal with 4 µm pore diameter graft was followed to 1 year. All heparin-eluting TEAGs were patent, but those with pore diameters larger than 4 µm began to dilate at week 4. Only scaffolds with a pore diameter of 4 µm resisted dilation and could do so for up to 1 year. At 8 weeks, the 10 µm pore graft had the highest density of cells in the electrospun layer and macrophages were the primary cell type present. This study highlights challenges in designing bioabsorbable TEAGs for the arterial environment in a large animal model. While larger pore diameter TEAGs promoted cell infiltration, neotissue could not regenerate rapidly enough to provide sufficient mechanical strength required to resist dilation. Future studies will be focused on evaluating a smaller pore design to better understand long-term remodeling and determine feasibility for clinical use. STATEMENT OF SIGNIFICANCE: In situ vascular tissue engineering relies on a biodegradable scaffold that encourages tissue regeneration and maintains mechanical integrity until the neotissue can bear the load. Species-specific differences in tissue regeneration and larger mechanical forces often result in graft failure when scaling up from small to large animal models. This study utilizes a slow-degrading electrospun PCL sheath to reinforce a tissue engineered arterials graft. Pore size, a property critical to tissue regeneration, was controlled by changing PCL fiber diameter and the resulting effects of these properties on neotissue formation and graft durability was evaluated. This study is among few to report the effect of pore size on vascular neotissue formation in a large animal arterial model and also demonstrate robust neotissue formation.

Economic Diversification Supported the Growth of Mongolia's Nomadic Empires.

Populations in Mongolia from the late second millennium B.C.E. through the Mongol Empire are traditionally assumed, by archaeologists and historians, to have maintained a highly specialized horse-facilitated form of mobile pastoralism. Until recently, a dearth of direct evidence for prehistoric human diet and subsistence economies in Mongolia has rendered systematic testing of this view impossible. Here, we present stable carbon and nitrogen isotope measurements of human bone collagen, and stable carbon isotope analysis of human enamel bioapatite, from 137 well-dated ancient Mongolian individuals spanning the period c. 4400 B.C.E. to 1300 C.E. Our results demonstrate an increase in consumption of C4 plants beginning at c. 800 B.C.E., almost certainly indicative of millet consumption, an interpretation supported by archaeological evidence. The escalating scale of millet consumption on the eastern Eurasian steppe over time, and an expansion of isotopic niche widths, indicate that historic Mongolian empires were supported by a diversification of economic strategies rather than uniform, specialized pastoralism.