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The carbapenem/beta-lactamase inhibitor meropenem-vaborbactam (MEV) used to treat complicated urinary tract infections and pyelonephritis in adults was approved in 2017 by the U.S. Food and Drug Administration (FDA). Here, we evaluated Vitek 2 MEV (bioMérieux, Durham, NC) compared to the reference broth microdilution (BMD) method. Of 449 Enterobacterales isolates analyzed per FDA/CLSI breakpoints, the overall performance was 98.2% essential agreement (EA), 98.7% category agreement (CA), and 0% very major errors (VME) or major errors (ME). For 438 FDA intended-for-use Enterobacterales isolates, performance was 98.2% EA, 98.6% CA, and 0% VME or ME. Evaluable EA was 81.0%, but with only 42 on-scale evaluable results. Individual species demonstrated EA and CA rates of ≥90% without any VME or ME. When evaluated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, overall Vitek 2 MEV performance for Enterobacterales and Pseudomonas aeruginosa demonstrated 97.3% EA, 99.2% CA, 2.3% VME, and 0.6% ME (after error resolution: 97.3% EA, 99.4% CA, 2.2% VME, and 0.4% ME) compared to the reference BMD method. Performance for P. aeruginosa included 92.2% EA, 97.4% CA, 0% VME, and 3.0% ME (after error resolution: 92.2% EA, 98.7% CA, 0% VME, and 1.5% ME). Performance for Enterobacterales included 98.2% EA, 99.6% CA, 3.0% VME, and 0.2% ME. Evaluable EA was 80.6% but was based on only 67 evaluable results. These findings support Vitek 2 MEV as an accurate automated system for MEV susceptibility testing of Enterobacterales and P. aeruginosa and could be an alternate solution to the manual-labor-intensive reference BMD method.

Tertiary education policy in Aotearoa New Zealand has been shaped by political, economic, and social ideologies. Although universities and polytechnics are both tertiary education providers, they do not occupy this space on an equal footing. There are differences in the qualifications offered, and the levels of monitoring and oversight required by government. The passing of the Education (Vocational Education and Training Reform) Amendment Act 2020 has underscored these differences. The subsequent establishment and naming of Te Pukenga, which translates as 'the skills', implies a policy direction for education provided by the polytechnic sector. Policy objectives for Vocational Education and Training (VET) aim at providing students with access to meaningful qualifications, decent work and economic and social inclusion. However, policy implementation is rarely straightforward. This article explores how the focus on skills implicit in the naming of Te Pukenga potentially makes this an aspirational rather than material policy goal.

Cortical spreading depolarizations (CSDs) are increasingly suspected to play an exacerbating role in a range of acute brain injuries, including stroke, possibly through their interactions with cortical blood flow. We use simultaneous wide-field imaging of neural activity and hemodynamics in Thy1-GCaMP6f mice to explore the neurovascular dynamics of CSDs during and following Rose Bengal-mediated photothrombosis. CSDs are observed in all mice as slow-moving waves of GCaMP fluorescence extending far beyond the photothrombotic area. Initial CSDs are accompanied by profound vasoconstriction and leave residual oligemia and ischemia in their wake. Later, CSDs evoke variable responses, from constriction to biphasic to vasodilation. However, CSD-evoked vasoconstriction is found to be more likely during rapid, high-amplitude CSDs in regions with stronger oligemia and ischemia, which, in turn, worsens after each repeated CSD. This feedback loop may explain the variable but potentially devastating effects of CSDs in the context of acute brain injury.

Despite a considerable expenditure of time and resources and significant advances in experimental models of disease, cancer research continues to suffer from extremely low success rates in translating preclinical discoveries into clinical practice. The continued failure of cancer drug development, particularly late in the course of human testing, not only impacts patient outcomes, but also drives up the cost for those therapies that do succeed. It is clear that a paradigm shift is necessary if improvements in this process are to occur. One promising direction for increasing translational success is comparative oncology-the study of cancer across species, often involving veterinary patients that develop naturally-occurring cancers. Comparative oncology leverages the power of cross-species analyses to understand the fundamental drivers of cancer protective mechanisms, as well as factors contributing to cancer initiation and progression. Clinical trials in veterinary patients with cancer provide an opportunity to evaluate novel therapeutics in a setting that recapitulates many of the key features of human cancers, including genomic aberrations that underly tumor development, response and resistance to treatment, and the presence of comorbidities that can affect outcomes. With a concerted effort from basic scientists, human physicians and veterinarians, comparative oncology has the potential to enhance the cost-effectiveness and efficiency of pipelines for cancer drug discovery and other cancer treatments.

BackgroundLower urinary tract transitional cell carcinoma (TCC) is an important but rarely described disease of cats.ObjectivesTo report the clinical characteristics, treatments, and outcomes in a cohort of cats with lower urinary tract TCC and to test identified variables for prognostic relevance.AnimalsOne-hundred eighteen client-owned cats with lower urinary tract carcinoma.MethodsMedical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed statistically.ResultsMedian age of affected cats was 15 years (range, 5.0-20.8 years) and median duration of clinical signs was 30 days (range, 0-730 days). The trigone was the most common tumor location (32/118; 27.1%) as assessed by ultrasound examination, cystoscopy, or both. Treatment was carried out in 73 of 118 (61.9%) cats. Metastatic disease was documented in 25 of 118 (21.2%) cats. Median progression-free survival and survival time for all cats were 113 days (95% confidence interval [CI], 69-153) and 155 days (95% CI, 110-222), respectively. Survival increased significantly (P

Harvested by advanced technical systems honed over decades of research and development, wind energy has become a mainstream energy resource. However, continued innovation is needed to realize the potential of wind to serve the global demand for clean energy. Here, we outline three interdependent, cross-disciplinary grand challenges underpinning this research endeavor. The first is the need for a deeper understanding of the physics of atmospheric flow in the critical zone of plant operation. The second involves science and engineering of the largest dynamic, rotating machines in the world. The third encompasses optimization and control of fleets of wind plants working synergistically within the electricity grid. Addressing these challenges could enable wind power to provide as much as half of our global electricity needs and perhaps beyond.

Frequency of feeding problems, gastrointestinal (GI) symptoms, challenging behavior, sensory problems and comorbid psychopathology were assessed using the following questionnaires: Screening Tool for Feeding Problems for Children, GI Symptoms Inventory, Behavior Problems Inventory Short Form, Short Sensory Profile, and Autism Spectrum Disorder-Comorbidity Child (ASD-CC) in 136 children and adolescents with ASD. Eighty-four percent had food selectivity, followed by food refusal (78.7%), rapid eating (76.5%), chewing problems (60.3%), food stealing (49.3%) and vomiting (19.1%). Higher rates of GI symptoms, challenging behavior, and sensory issues were found in those who presented with rapid eating, food refusal and food stealing than those without these problems. Comorbid psychopathology predicted rapid eating, food selectivity and food refusal.

Abstract. High-resolution, well-dated climate archives provide anopportunity to investigate the dynamic interactions of climate patternsrelevant for future projections. Here, we present data from a new, annuallydated ice core record from the eastern Ross Sea, named the Roosevelt IslandClimate Evolution (RICE) ice core. Comparison of this record with climatereanalysis data for the 1979–2012 interval shows that RICE reliably capturestemperature and snow precipitation variability in the region. Trends over thepast 2700 years in RICE are shown to be distinct from those in WestAntarctica and the western Ross Sea captured by other ice cores. For most ofthis interval, the eastern Ross Sea was warming (or showing isotopicenrichment for other reasons), with increased snow accumulation and perhapsdecreased sea ice concentration. However, West Antarctica cooled and thewestern Ross Sea showed no significant isotope temperature trend. Thispattern here is referred to as the Ross Sea Dipole. Notably, during theLittle Ice Age, West Antarctica and the western Ross Sea experienced colderthan average temperatures, while the eastern Ross Sea underwent a period ofwarming or increased isotopic enrichment. From the 17th century onwards, thisdipole relationship changed. All three regions show current warming, withsnow accumulation declining in West Antarctica and the eastern Ross Sea butincreasing in the western Ross Sea. We interpret this pattern as reflectingan increase in sea ice in the eastern Ross Sea with perhaps the establishmentof a modern Roosevelt Island polynya as a local moisture source for RICE.

Abstract. High-resolution, well-dated climate archives provide an opportunity to investigate the dynamic interactions of climate patterns relevant for future projections. Here, we present data from a new, annually-dated ice core record from the eastern Ross Sea. Comparison of the Roosevelt Island Climate Evolution (RICE) ice core records with climate reanalysis data for the 1979–2012 calibration period shows that RICE records reliably capture temperature and snow precipitation variability of the region. RICE is compared with data from West Antarctica (West Antarctic Ice Sheet Divide Ice Core) and the western (Talos Dome) and eastern (Siple Dome) Ross Sea. For most of the past 2,700 years, the eastern Ross Sea was warming with perhaps increased snow accumulation and decreased sea ice extent. However, West Antarctica cooled whereas the western Ross Sea showed no significant temperature trend. From the 17th Century onwards, this relationship changes. All three regions now show signs of warming, with snow accumulation declining in West Antarctica and the eastern Ross Sea, but increasing in the western Ross Sea. Analysis of decadal to centennial-scale climate variability superimposed on the longer term trend reveal that periods characterised by opposing temperature trends between the Eastern and Western Ross Sea have occurred since the 3rd Century but are masked by longer-term trends. This pattern here is referred to as the Ross Sea Dipole, caused by a sensitive response of the region to dynamic interactions of the Southern Annual Mode and tropical forcings.

Introduction: On intensive grassland dairy farms in high rainfall areas with poorly drained soils, networks of open drainage channels linked to in-field drainage systems are needed to enable farm operations. Nitrogen and phosphorus point and diffuse sources may be connected to this open drainage channel network along surface and subsurface pathways, with negative impacts upon delivery to the downstream aquatic system. Methods: This study developed a semi-quantitative risk assessment model by: (1) selecting parameters (categorical or continuous) representing the nutrient transfer continuum and (2) scoring (relative magnitude and impact) the risk of nutrient source connectivity and delivery for every open drainage channel section across seven dairy farms. Results and Discussion: A Risk Index Classification System consisting of low, medium, high, or very high-risk class was developed, with high or above requiring a mitigation plan. Results showed that 23%, 68%, 9% and 0% of all open drainage channels on study farms were identified as low, moderate, high and very highrisk, respectively. A range from 2% to 25% per farm of the open drainage channels was classified as high-risk that potentially needed mitigation, although none was identified as very high-risk. Two-thirds of the high-risk open drainage channels were connected to the farmyards, with potential for high nutrient loss from point sources. A combined approach of source management and targeted breaking of the pathway (e.g., in-channel filters, water diversion bars) may help minimise nutrient losses from high risk open drainage channels on poorly draining soils. [ABSTRACT FROM AUTHOR]