The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, ...or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H
-receptor antagonists (H
blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H
blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m
and of incident CKD (hazard ratio HR, 1.22; 95% confidence interval 95% CI, 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31-90, 91-180, 181-360, and 361-720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H
blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.
Concerns over groundwater depletion and ecosystem degradation have led to the incorporation of the concept of groundwater sustainability as a groundwater policy instrument in several water codes and ...management directives worldwide. Because sustainable groundwater management is embedded within integrated, co-evolving hydrological, ecological, and socioeconomic systems, implementing such policies remains a challenge for water managers and the scientific community. The problem is further exacerbated when participatory processes are lacking, resulting in a communication gap among water authorities, scientists, and the broader community. This paper provides a systematic review of the concept of groundwater sustainability, and situates this concept within the calls from the hydrologic literature for more participatory and integrated approaches to water security. We discuss the definition of groundwater sustainability from both a policy and scientific perspective, tracing the evolution of this concept from safe yield, to sustainable groundwater management. We focus on the diversity of societal values related to groundwater sustainability, and the typology of the aquifer performance and governance factors. In addition, we systematically review the main components of an effective scientific evaluation of groundwater sustainability policy, which are multi-process modeling, uncertainty analysis, and participation. We conclude that effective groundwater sustainability policy implementation requires an iterative scientific evaluation that (i) engages stakeholders in a participatory process through collaborative modeling and social learning; (ii) provides improved understanding of the coevolving scenarios between surface water-groundwater systems, ecosystems, and human activities; and (iii) acknowledges and addresses uncertainty in our scientific knowledge and the diversity of societal preferences using multi-model uncertainty analysis and adaptive management. Although the development of such a transdisciplinary research approach, which connects policy, science, and practice for groundwater sustainability evaluation, is still in its infancy worldwide, we find that research towards groundwater sustainability is growing at a much faster rate than groundwater research as a whole.
Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle ...and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of FabB/F, a critical enzyme in fatty acid synthesis, did not affect parasite blood stage replication, mosquito stage development and initial infection in the liver. This was confirmed by knockout of FabZ, another critical FAS II enzyme. However, FAS II-deficient Plasmodium yoelii liver stages failed to form exo-erythrocytic merozoites, the invasive stage that first initiates blood stage infection. Furthermore, deletion of FabI in the human malaria parasite Plasmodium falciparum did not show a reduction in asexual blood stage replication in vitro. Malaria parasites therefore depend on the intrinsic FAS II pathway only at one specific life cycle transition point, from liver to blood.
Bovine respiratory disease (BRD) is one of the leading causes of death in dairy heifers. The objective of this prospective cohort study was to characterize the epidemiology of BRD in preweaned dairy ...calves and to identify management practices associated with decreased risk of BRD. Dairies were chosen for the study based on management practices, location, size, and willingness to participate. A total of 6 dairies, ranging in size from 700 to 3,200 milking cows, in 6 counties across California's Central Valley, were enrolled in the study for at least 1 year. A total of 11,945 calves were born on the study dairies and followed until weaning. Incidence of BRD was estimated using treatment records. Trained study personnel performed comprehensive calf management surveys and estimated BRD prevalence on every dairy at least once every season. A shared frailty model was used to model the associations between management practices and BRD hazard. The final models included data from complete records of 11,470 calves. The overall BRD study period prevalence across the study herds was 22.8%. The mean BRD incidence density rate on all the study dairies was 0.17 BRD cases 95% confidence interval (CI) = 0.16–1.74 per calf-month at risk. The shared frailty model identified that feeding only waste or saleable milk (compared with use of milk replacer), feeding over 3.8 L of milk per day to calves under 21 d of age, frequent changing of maternity pen bedding, and administration of modified live or killed BRD vaccines to dams before calving significantly reduced the risk of BRD. Risk factors for BRD included housing calves in wooden hutches with metal roofs, compared with all-wood hutches, twin births, and perception of dust occurring “regularly,” as reported by calf managers, compared with a perception of “no dust” in the calf-raising area. All 4 seasons were analyzed, and both summer (hazard ratio = 1.15; 95% CI = 1.01 to 1.32) and spring (hazard ratio = 1.26; 95% CI = 1.11 to 1.44) were associated with a higher risk of BRD compared with winter. The current longitudinal study identified specific housing and feeding practices that could be modified to decrease risk of BRD. In addition, season was observed to have a strong effect on calves' risk of developing BRD on California dairies.
The world's appetite for analyzing massive amounts of structured and unstructured data has grown dramatically. The computational demands of these abundant-data applications, such as deep learning, ...far exceed the capabilities of today's computing systems and are unlikely to be met with isolated improvements in transistor or memory technologies, or integrated circuit architectures alone. To achieve unprecedented functionality, speed, and energy efficiency, one must create transformative nanosystems whose architectures are based on the salient properties of the underlying nanotechnologies. Our Nano-Engineered Computing Systems Technology (N3XT) approach makes such nanosystems possible through new computing system architectures leveraging emerging device (logic and memory) nanotechnologies and their dense 3-D integration with fine-grained connectivity to immerse computing in memory and new logic devices (such as carbon nanotube field-effect transistors for implementing high-speed and low-energy logic circuits) as well as high-density nonvolatile memory (such as resistive memory), and amenable to ultradense (monolithic) 3-D integration of thin layers of logic and memory devices that are fabricated at low temperature. In addition, we explore the use of several device and integration technologies in the N3XT beyond the specific ones mentioned earlier that are also used in our main nanosystem prototypes. We also present an efficient resiliency technique to overcome endurance challenges in certain resistive memory technologies. N3XT hardware prototypes demonstrate the practicality of our architectures. We evaluate the benefits of the N3XT using a simulation framework calibrated using experimental measurements. System-level energy-delay product of common implementations of abundant-data workloads improves by three orders of magnitude in the N3XT compared with conventional architectures. These improvements impact a broad range of application workloads and architecture configurations, from embedded systems to the cloud.
Mortality in preweaned dairy calves is a significant source of economic loss for dairy producers. In particular, bovine respiratory disease (BRD) is a leading cause of death in preweaned dairy ...calves. The objectives of this study were to investigate management practices and their effects on mortality, both that specifically attributed to BRD and overall mortality due to all causes, in preweaned dairy calves. Rates of failure of passive transfer of immunity (FPT) are also reported. The study consisted of a convenience sample of 5 dairies across California, selected based on management practices, calf records, location, and size. Trained study personnel performed comprehensive calf management surveys on every dairy at least once every season. Calves were enrolled in the study at birth and followed until weaning. Mixed-effect logistic regression models were specified for the outcomes all-cause mortality (any death before weaning) and mortality attributed to BRD. The 2 final models included a total of 11,470 calves that were born on the study dairies and followed until weaning. The study cohort's overall crude mortality was 2.8%, with crude mortality of individual dairies ranging from 1.7 to 7.2%. The proportion of mortality attributed to BRD was 19.3%, with a range of 0 to 27.1% on the study dairies. Increasing the frequency of changing maternity pen bedding was associated with a decreased risk of mortality due to BRD. Calves diagnosed with BRD in the spring had an increased risk of mortality compared with calves born in the summer; mortality in calves with fall and winter BRD diagnoses did not different significantly from that in summer. Season of mortality was not significant in either model. Feeding ≥5.7 L of milk per day per calf (vs. ≤3.7 L/d) decreased the risk of mortality in calves over 21 d of age. Twins had a 68% increased risk of all-cause mortality compared with calves born as singletons. Both mortality models showed an association between administration of a modified live vaccine in dams (targeting BRD pathogens) and a decreased risk of mortality in calves. Using a serum total protein cut-off of 5.2 g/dL, 16.8% of calves had FPT, with a mean serum total protein concentration of 5.94 ± 0.06 g/dL across all calves sampled.
The control of malaria parasite transmission from mosquitoes to humans is hampered by decreasing efficacies of insecticides, development of drug resistance against the last-resort antimalarials, and ...the absence of effective vaccines. Herein, the anti-plasmodial transmission blocking activity of a recombinant Aspergillus oryzae (A. oryzae-R) fungus strain, which is used in human food industry, was investigated in laboratory-reared Anopheles stephensi mosquitoes. The recombinant fungus strain was genetically modified to secrete two anti-plasmodial effector peptides, MP2 (midgut peptide 2) and EPIP (enolase-plasminogen interaction peptide) peptides. The transstadial transmission of the fungus from larvae to adult mosquitoes was confirmed following inoculation of A. oryzae-R in the water trays used for larval rearing. Secretion of the anti-plasmodial effector peptides inside the mosquito midguts inhibited oocyst formation of P. berghei parasites. These results indicate that A. oryzae can be used as a paratransgenesis model carrying effector proteins to inhibit malaria parasite development in An. stephensi. Further studies are needed to determine if this recombinant fungus can be adapted under natural conditions, with a minimal or no impact on the environment, to target mosquito-borne infectious disease agents inside their vectors.
COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from ...50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.
Accurate reference evapotranspiration (ET
0
) estimation has an effective role in reducing water losses and raising the efficiency of irrigation water management. The complicated nature of the ...evapotranspiration process is illustrated in the amount of meteorological variables required to estimate ET
0
. Incomplete meteorological data is the most significant challenge that confronts ET
0
estimation. For this reason, different machine learning techniques have been employed to predict ET
0
, but the complicated structures and architectures of many of them make ET
0
estimation very difficult. For these challenges, ensemble learning techniques are frequently employed for estimating ET
0
, particularly when there is a shortage of meteorological data. This paper introduces a powerful super learner ensemble technique for ET
0
estimation, where four machine learning models: Extra Tree Regressor, Support Vector Regressor, K-Nearest Neighbor and AdaBoost Regression represent the base learners and their outcomes used as training data for the meta learner. Overcoming the overfitting problem that affects most other ensemble methods is a significant advantage of this cross-validation theory-based approach. Super learner performances were compared with the base learners for their forecasting capabilities through different statistical standards, where the results revealed that the super learner has better accuracy than the base learners, where different combinations of variables have been used whereas Coefficient of Determination (R
2
) ranged from 0.9279 to 0.9994 and Mean Squared Error (MSE) ranged from 0.0026 to 0.3289 mm/day but for the base learners R
2
ranged from 0.5592 to 0.9977, and MSE ranged from 0.0896 to 2.0118 mm/day therefore, super learner is highly recommended for ET
0
prediction with limited meteorological data.
The IPBES Global Assessment: Pathways to Action Ruckelshaus, Mary H.; Jackson, Stephen T.; Mooney, Harold A. ...
Trends in ecology & evolution (Amsterdam),
20/May , Letnik:
35, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The first Global Assessment of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) found widespread, accelerating declines in Earth’s biodiversity and ...associated benefits to people from nature. Addressing these trends will require science-based policy responses to reduce impacts, especially at national to local scales. Effective scaling of science-policy efforts, driven by global and national assessments, is a major challenge for turning assessment into action and will require unprecedented commitment by scientists to engage with communities of policy and practice. Fulfillment of science’s social contract with society, and with nature, will require strong institutional support for scientists’ participation in activities that transcend conventional research and publication.
The IPBES Global Assessment released in the spring of 2019 is a significant milestone for the international scientific community; the critical challenge now is to disseminate and apply its findings at national and local scales where most policy and management decisions affecting biodiversity and ecosystem services are made.Effective, enduring action from assessments requires collaborative, multidisciplinary science-policy processes that frame and cogenerate knowledge with decision makers and stakeholders from many sectors.Examples of assessments driving policy responses to recover biodiversity and ecosystem services highlight the need for significant, long-term commitments by governments, non-governmental organizations (NGOs), the private sector, civil society, and the scientific community.
PDF
