Donor CD47 controls T cell alloresponses and is required for tolerance induction following hepatocyte allotransplantation

CD47-deficient hepatocyte transplantation induces rapid innate immune cell activation and subsequent associated graft loss in syngeneic recipients. However, the role of donor CD47 in regulation of T-cell alloresponses is poorly understood. We addressed this question by assessing OVA-specific immune responses in mice following hepatocyte transplantation from CD47-competent or -deficient OVAtransgenic donors. Compared to sham-operated controls, intrasplenic transplantation of CD47-deficient OVA+ hepatocytes significantly accelerated rejection of OVA+ skin grafted 7 days after hepatocyte transplantation. In contrast, mice receiving CD47-competent OVA+ hepatocytes showed prolonged and even indefinite survival of OVA+ skin allografts. T cells from mice receiving CD47-deficient, but not CD47-competent, OVA+ hepatocytes showed significantly enhanced responses to OVA+ stimulators compared to sham-operated controls. In contrast to the production of tolerogenic cytokines (IL-4 and IL-10) in the recipients of CD47-competent hepatocytes, mice receiving CD47-deficient hepatocytes showed elevated production of IFN-γ and IL-1α. Moreover, significant expansion of myeloid-derived suppressor cells was detected in the recipients of CD47-competent hepatocytes, which was required for tolerance induction in these mice. Thus, donor CD47 plays an important role in the control of T-cell alloresponses and tolerance induction following hepatocyte transplantation. Our data also suggest that intrasplenic hepatocyte transplantation may provide a means to induce allograft tolerance

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018

Background Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.publishedVersio

Mapping male circumcision for HIV prevention efforts in sub-Saharan Africa

Background HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50–60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15–49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence. Methods We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15–49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units. Results We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas. Conclusions Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa

Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-Saharan Africa, 2000–18 : a modelling study

Background: High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. Methods: In this modelling study, we developed a framework that used the geographically specific HIV prevalence data collected in seroprevalence surveys and antenatal care clinics to train a model that estimates HIV incidence and mortality among individuals aged 15–49 years. We used a model-based geostatistical framework to estimate HIV prevalence at the second administrative level in 44 countries in sub-Saharan Africa for 2000–18 and sought data on the number of individuals on antiretroviral therapy (ART) by second-level administrative unit. We then modified the Estimation and Projection Package (EPP) to use these HIV prevalence and treatment estimates to estimate HIV incidence and mortality by second-level administrative unit. Findings: The estimates suggest substantial variation in HIV incidence and mortality rates both between and within countries in sub-Saharan Africa, with 15 countries having a ten-times or greater difference in estimated HIV incidence between the second-level administrative units with the lowest and highest estimated incidence levels. Across all 44 countries in 2018, HIV incidence ranged from 2 ·8 (95% uncertainty interval 2·1–3·8) in Mauritania to 1585·9 (1369·4–1824·8) cases per 100 000 people in Lesotho and HIV mortality ranged from 0·8 (0·7–0·9) in Mauritania to 676· 5 (513· 6–888·0) deaths per 100 000 people in Lesotho. Variation in both incidence and mortality was substantially greater at the subnational level than at the national level and the highest estimated rates were accordingly higher. Among second-level administrative units, Guijá District, Gaza Province, Mozambique, had the highest estimated HIV incidence (4661·7 [2544·8–8120·3]) cases per 100000 people in 2018 and Inhassunge District, Zambezia Province, Mozambique, had the highest estimated HIV mortality rate (1163·0 [679·0–1866·8]) deaths per 100 000 people. Further, the rate of reduction in HIV incidence and mortality from 2000 to 2018, as well as the ratio of new infections to the number of people living with HIV was highly variable. Although most second-level administrative units had declines in the number of new cases (3316 [81· 1%] of 4087 units) and number of deaths (3325 [81·4%]), nearly all appeared well short of the targeted 75% reduction in new cases and deaths between 2010 and 2020. Interpretation: Our estimates suggest that most second-level administrative units in sub-Saharan Africa are falling short of the targeted 75% reduction in new cases and deaths by 2020, which is further compounded by substantial within-country variability. These estimates will help decision makers and programme implementers expand access to ART and better target health resources to higher burden subnational areas

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000-2018

BACKGROUND: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA. METHODS: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. RESULTS: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. CONCLUSIONS: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018

Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA

Spread of Hantavirus in humans due to anthropogenic environmental degradation: a systematic review.

Imperial Users onlyDistinctio

Topography Changes of the University of Washington Bothell Campus

The City of Bothell provided historical topographical data of the University of Washington Bothell (UWB) campus for this group to analyze the changing landscape and elevation of the area. This poster analyzes topographical vector data of the UWB campus for the years 2000, 2008, and 2015. The data were collected by the City of Bothell using Orthoimagery and LiDAR data. Goals for this project included: 1) derive digital elevation models that most accurately represent the UWB campus topography using the Topo-to-Raster technique in an ArcMap environment and 2) compare changes in elevation over time. The intent is to account for the errors that may arise when interpolating three datasets that were collected using two different remote sensing techniques. A map algebra framework is used to compare changes in topography between 2000 and 2015. The campus has had several buildings and a new parking lot added in the time these data were collected, and this group expects to see the most changes in topography where there has been construction. Since the main UWB campus sits on a steep incline, this group expects to see erosion and the effects of compensating for this erosion, as having the most impact in shifting contour lines. Future work on this topic will include comparing vegetation coverage over the years and investigate how they relate to topographic and hydrological changes

Characteristics of “Guangyuan-Wangcang” trough during Late Middle Permian and its petroleum geological significance in northern Sichuan Basin, SW China

Based on outcrop characteristics, combined with regional tectonic background, drilling and geophysical data, the sedimentary characteristics of the Middle Permian Maokou Formation in the northern Sichuan Basin was studied by means of macroscopic and microscopic observation, geochemical element test, total organic carbon content and vitrinite reflectance measurement. There is a set of deep-water sediments rich in organic matter in the Guangyuan-Wangcang area of northern Sichuan during the late depositional period of the Middle Permian Maokou Formation. The strata are distributed from northwest to southeast, with thickness of 10–30 m, mainly composed of siliceous rocks and siliceous mudstones, intercalated with gravity flow deposits. Siliceous rocks and siliceous mudstones are characterized by thin single layer, flat bedding and rich siliceous radiolarians, calthrop and brachiopod with small body and thin shell, belonging to the typical sedimentary characteristics of deep-water trough facies. The contents of Cu, Co, Mo, Ni and the ratio of Ni to Co in the geochemical tests all indicate that the siliceous rocks are products of deep-water reducing environment. The TOC value ranges from 3.21% to 8.19%, with an average of 5.53%, indicating that the siliceous rocks have good hydrocarbon generation ability. The south side of the trough is in platform margin facies with high energy, and the sediments are mainly thick massive micritic-calcsparite biogenic (clastic) limestone, which is conducive to the formation and evolution of the reservoir. During the late sedimentary period of the Maokou Formation, the northward subduction and extension of the oceanic crust at the northwestern margin of the Yangtze Plate provided the internal dynamic conditions for the formation of the “Guangyuan-Wangcang” trough. According to the location, sedimentary characteristics and formation dynamics of the trough, it is similar to the “Kaijiang-Liangping” trough during Late Permian proposed by previous researchers. It is believed that the “Kaijiang-Liangping” trough already had its embryonic form during the Late Middle Permian

Reservoir characteristics and genetic differences between the second and fourth members of Sinian Dengying Formation in northern Sichuan Basin and its surrounding areas

This study investigated the characteristics and genesis of reservoirs in the 2nd and 4th members of Sinian Dengying Formation in northern Sichuan and its surrounding areas, on the basis of outcrop, drilling cores and thin section observation and geochemical analysis. The reservoirs of 2nd member are distributed in the middle part of the stratum. The reservoir quality is controlled by supergene karst and the distribution of mound-shoal complex. The bedded elongated isolated algal framework solution-cave and the residual “grape-lace” cave, which are partially filled with multi-stage dolosparite, constituted the main reservoir space of the 2nd member. There is no asphalt distribution in the pores. The pore connectivity is poor, and the porosity and permeability of the reservoir is relatively low. The reservoirs of 4th member were distributed in the upper and top part of the stratum. The reservoir quality is controlled by burial dissolution and the distribution of mound-shoal complex. The bedded algal framework solution-pores or caves, intercrystalline pores and intercrystalline dissolved pores constituted the main reservoir space of the 4th member. It's partially filled with asphalt and quartz, without any dolosparite fillings in the pores and caves. The pore connectivity is good. Most of the 4th member reservoirs had medium-low porosity and low permeability, and, locally, medium-high porosity and medium permeability. Affected by the development of mound-shoal complex and heterogeneous dissolution, the platform margin along Ningqiang, Guangyuan, Jiange and Langzhong is the most favorable region for reservoir development. Deep buried Dengying Formation in the guangyuan and langzhong areas should be the most important hydrocarbon target for the future exploration. Key words: Sichuan Basin, northern Sichuan area, Sinian, Dengying Formation, mound-shoal complex, supergene karst, burial dissolution, reservoi