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Objectives were to determine the influence of a vitamin and mineral supplement (VTM), an energy supplement (NRG), and day post-artificial insemination (DPAI) on concentrations of glucose and non-esterified fatty acids (NEFA) in beef heifers. Cross-bred heifers (n = 72; initial weight = 351.2 kg) were assigned to 4 treatments arranged as a 2 × 2 factorial with main factors of VTM and NRG supplement. Treatments were: 1) control (no VTM or NRG), 2) VTM (initiated 71 to 106 before breeding) only, 3) NRG (initiated at breeding) only, and 4) VTM and NRG. Heifers were synchronized then bred via artificial insemination on d 0. Blood was drawn on d -9, 14, 28, and 42 from all heifers and on d 56, 70, and 84 from pregnant heifers (n = 31). Plasma samples were analyzed for concentrations of glucose and NEFA. Data were analyzed using the MIXED procedure in SAS. There were no interactions between VTM, NRG, or DPAI (P > 0.05). In addition, pregnancy status did not influence concentrations of glucose or NEFA (P > 0.05). There were no effects (P > 0.35) of VTM on glucose or NEFA concentrations. Energy supplementation increased (P = 0.012) glucose and decreased (P = 0.013) NEFA concentrations. Glucose concentrations were greatest at d -9, decreased through d 42, and then, on d 70 and 84 increased to levels similar to d -9 (81.9, 76.1, 73.6, 73.7, 74.3, 76.2, and 78.4 ± 2.97 for d -9, 14, 28, 42, 56, 70, and 84, respectively). Concentrations of NEFA were greater (P < 0.01) at d -9 compared with 14, 28, 42, 56, and 70, and concentrations on d 84 were greater (P < 0.01) than all other days. In conclusion, glucose and NEFA were affected by NRG and DPAI, but not VTM.

Sauer et al discuss the effects of a vitamin and mineral supplement and an energy supplement on concentrations of glucose and non-esterified fatty acids in artificially inseminated beef heifers up to d 84 post-insemination. They aim to determine the influence of a vitamin and mineral supplement (VTM), an energy supplement (NRG), and day post-artificial insemination (DPAI) on concentrations of glucose and non-esterified fatty acids (NEFA) in beef heifers. They conclude that glucose and NEFA were affected by NRG and DPAI, but not VTM.

The objective was for nurses who are covering unfamiliar oncology clinics to increase the accuracy of advice and decrease time to respond to patients calling about timing of specific medications with their complex oral chemotherapy regimens. Oral chemotherapy regimens are becoming increasingly complex, and along with that comes questions about how and when to take the pills. At Moores Cancer Center (MCC), there are 9 specialty cancer groups. It is not uncommon for a covering nurse to be unfamiliar with the particular chemo regime the patient is undergoing. With the goal of increasing accuracy and decreasing delays in time to respond to patients questions about timing of complicated chemo, a calendar smart phrase tool has been developed. This performance improvement project utilized the PDSA approach. .Txcal was created in conjunction with input from PharmDs, MCC nurses, physicians, and Epic staff. This creates the ability to place a calendar into an after visit summary, or mychart message to patients which then has the specific chemotherapy names placed on the appropriate dates. A 10 question survey was sent to MCC nurses prior to the implementation of the .Txcal smartphrase to establish a baseline. Over the course of 3 months, educational sessions and one on one meetings were held introducing the smartphrase. A 10 question survey was immediately sent out after the educational session, as well as sent out 3 months after the education to evaluate effectiveness. As a result of the .txcal smartphrase, nurses were able to respond to questions much more quickly. Response times went from \"hours and days\" to \"seconds and minutes\". There was a significant decrease in time taken to answer the questions of which medications should be taken on any given day; from 81 and 220 seconds pre-intervention to 15 and 21 seconds post intervention. Accuracy in advice was also increased. Prior to implementing the .txcal smartphrase, only 79% of the time the covering nurse was able to correctly advise on which date an oral chemotherapy should be stopped. After the implementation, 100% identified correctly which date an oral chemotherapy should be stopped. The .txcal smartphrase increased accuracy of nurses covering for other teams when advising oral chemotherapy timing with patients/family members, as well as decreased the time it took to respond.

In this population-based cohort study that included data on all live births in Brazil from 2015 to 2018, infants with congenital Zika syndrome had substantially higher mortality over the first 3 years of life than those without the syndrome.

Species extinctions have defined the global biodiversity crisis, but extinction begins with loss in abundance of individuals that can result in compositional and functional changes of ecosystems. Using multiple and independent monitoring networks, we report population losses across much of the North American avifauna over 48 years, including once-common species and from most biomes. Integration of range-wide population trajectories and size estimates indicates a net loss approaching 3 billion birds, or 29% of 1970 abundance. A continent-wide weather radar network also reveals a similarly steep decline in biomass passage of migrating birds over a recent 10-year period. This loss of bird abundance signals an urgent need to address threats to avert future avifaunal collapse and associated loss of ecosystem integrity, function, and services.

Chinese investments into fossil fuel-based electricity generation capacity under its belt and road initiative will create lock-in for decades. Despite China’s recent rise as major public finance provider for the electricity sector of the developing world and the related environmental impacts, there is limited knowledge of the extent and characteristics of non-Chinese participation in Chinese-funded projects. We apply complexity theory approaches and network modeling on a new dataset that links funding activities of developmental institutions (Chinese developmental institutions (CDIs), Western-backed multilateral development banks (MDBs)) and the involvement of companies in different roles (i.e., as direct investors, contractors, equipment suppliers, and other service providers) to power plants around the world at the unit-level (1999–2020). Previous literature suggests that CDI funded projects show preference to Chinese commercial partners, but we find more than 70% include non-Chinese participants. This also applies for fossil-fuel based technologies where we observe increasing shares of international actors that together account for nearly every third commercial linkage. However, involvement levels and interaction patterns not only differ by technologies (fossils, hydro, non-hydro renewable, nuclear) but also by the time period and types of commercial partners and we observe overall convergence between the CDI- and MDB-supported power plant networks over time. The decreasing involvement of Chinese companies in CDI-funded projects, across technologies, in favor of increasing Western involvement, has important implications for development and climate policy on which we elaborate. However, the failure of both MDB and CDI funding to promote domestic company involvement in the recipient countries may be the largest failing of both sets of agencies in the pursuit of development outcomes.

Molecular mechanisms driving disease course and response to therapy in ulcerative colitis (UC) are not well understood. Here, we use RNAseq to define pre-treatment rectal gene expression, and fecal microbiota profiles, in 206 pediatric UC patients receiving standardised therapy. We validate our key findings in adult and paediatric UC cohorts of 408 participants. We observe a marked suppression of mitochondrial genes and function across cohorts in active UC, and that increasing disease severity is notable for enrichment of adenoma/adenocarcinoma and innate immune genes. A subset of severity genes improves prediction of corticosteroid-induced remission in the discovery cohort; this gene signature is also associated with response to anti-TNFα and anti-α 4 β 7 integrin in adults. The severity and therapeutic response gene signatures were in turn associated with shifts in microbes previously implicated in mucosal homeostasis. Our data provide insights into UC pathogenesis, and may prioritise future therapies for nonresponders to current approaches. The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved Escherichia coli growing on glycolytic or gluconeogenic carbon sources to the selective pressure of three different antibiotics. Profiling more than 500 intracellular and extracellular putative metabolites in 190 evolved populations revealed that carbon and energy metabolism strongly constrained the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. To interpret and explore the space of metabolome changes, we developed a novel constraint‐based modeling approach using the concept of shadow prices. This analysis, together with genome resequencing of resistant populations, identified condition‐dependent compensatory mechanisms of antibiotic resistance, such as the shift from respiratory to fermentative metabolism of glucose upon overexpression of efflux pumps. Moreover, metabolome‐based predictions revealed emerging weaknesses in resistant strains, such as the hypersensitivity to fosfomycin of ampicillin‐resistant strains. Overall, resolving metabolic adaptation throughout antibiotic‐driven evolutionary trajectories opens new perspectives in the fight against emerging antibiotic resistance. Synopsis Bacterial metabolism constrains the evolution of antibiotic resistance. A modeling approach is developed to interpret the functionality of metabolic rewiring in resistance‐evolving E. coli growing on glycolytic or gluconeogenic carbon sources from metabolomics data. Large‐scale untargeted metabolome profiling reveals metabolic adaptations in 190 evolved antibiotic‐resistant E. coli populations, in part as compensation for consequences of the primary resistance mechanisms. Carbon and energy metabolism strongly constrain the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. A novel constraint‐based modeling approach, together with genome re‐sequencing of resistant populations, identifies condition‐dependent compensatory mechanisms. Graphical Abstract Bacterial metabolism constrains the evolution of antibiotic resistance. A modeling approach is developed to interpret the functionality of metabolic rewiring in resistance‐evolving E. coli growing on glycolytic or gluconeogenic carbon sources from metabolomics data.

LAG-3 (Lymphocyte activation gene 3) protein is a checkpoint receptor that interacts with LSEC-tin, Galectin-3 and FGL1. This interaction leads to reduced production of IL-2 and IFN-γ. LAG-3 is widely expressed in different tumor types and modulates the tumor microenvironment through immunosuppressive effects. Differential expression in various tumor types influences patient prognosis, which is often associated with coexpression with immune checkpoint inhibitors, such as TIM-3, PD-1 and CTLA-4. Here, we discuss expression profiles in different tumor types. To date, many clinical trials have been conducted using LAG-3 inhibitors, which can be divided into anti-LAG-3 monoclonal antibodies, anti-LAG-3 bispecifics and soluble LAG-3-Ig fusion proteins. LAG-3 inhibitors supress T-cell proliferation and activation by disallowing for the interaction between LAG-3 to MHC-II. The process enhances anti-tumor immune response. In this paper, we will review the current state of knowledge on the structure, function and expression of LAG-3 in various types of cancer, as well as its correlation with overall prognosis, involvement in cell-based therapies and experimental medicine. We will consider the role of compounds targeting LAG-3 in clinical trials both as monotherapy and in combination, which will provide data relating to the efficacy and safety of proposed drug candidates.

Public and scientific consensus about climate change do not align. Problematically, higher scientific knowledge has been associated with lower acceptance of climate information among those with more conservative socio-political ideologies. Positive attitudes towards science can attenuate this effect. We investigated the association between endorsement of scientific inquiry (ESI) and decision-making with scientific evidence about climate policies. Participants rated support for 16 climate policies accompanied by weaker or stronger evidence. In study 1 (N = 503), higher ESI was associated with greater discernment between strongly and weakly evidenced climate policies, irrespective of worldview. In studies 2 (N = 402) and 3 (N = 600), an ESI intervention improved discrimination, and, in study 3, increased ESI specifically for hierarchical/individualistic participants. Unlike ESI, the link between scientific knowledge and evaluation of evidence was influenced by worldview. Increasing ESI might improve the evaluation of scientific evidence and increase public support for evidence-based climate policies.