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The learning curve of nurse practitioners (NPs) to accurately diagnose paediatric distal forearm fractures using point-of-care ultrasound (POCUS) was investigated.Each NP's learning curve was calculated as cumulative diagnostic accuracy against a number of scans performed. The curve's plateau represented the attainment of competency. Secondary outcomes were the comparisons before and after this cut-off of diagnostic accuracy, classification of diagnostic errors, pain scores, duration and preference.Five NPs performed 201 POCUS studies with diagnostic accuracy plateauing at 90%, providing a 'cut-off' point at scan 15. Accuracy of POCUS scanning before and after the fifteenth scan was 81% (95% CI 70%-89%) and 90% (95% CI 84%-94%), respectively, demonstrating 9% improvement (P = 0.07). There was a 10% reduction in image interpretation errors. After fifteen scans, POCUS became faster (mean difference (MD) 2.6 min [95% CI 2.0-3.3], P 0.001), less painful (MD 0.61 points FPSR scale [95% CI 0.04-1.18], P = 0.04) and more preferred by NPs (63% vs 77%, P = 0.03).The learning curve of POCUS-novice NPs independently scanning paediatric distal forearm injuries plateaued with mean diagnostic accuracy of 90% after 15 scans, suggesting competency was attained at this cut-off, supported by higher accuracy, being faster, less painful and more preferred by NPs. Future training packages in forearm POCUS should further address image interpretation and provide ongoing expert feedback.The findings from this study suggest that competency in paediatric distal forearm POCUS can be attained by novices after a short training course and approximately 15 scans.

Any analysis of a “National Educational System” reveals a highly complex social production system that is neither a hierarchical organization, nor a market, nor simply a misaligned system of principals and agents. It is, instead, a complex array of social actors bound together through various social structures and processes on one hand, and important functional relationships on the other. In approaching the challenge of moving that system towards sustained productivity gains, national governments naturally fall prey to the assumption that, in the principal/agent framework they are the principals of the system. But, as we have seen empirically, this idea overestimates the capacities of most central governments in developing countries (Pritchett 2013, Pritchett 2015, Moore and Spivack 2022). The world at large has learned that it is hard to centrally manage complex economies to produce economic prosperity and social equity. It is not obvious that the search for educational improvement is any less difficult. Of course, it is not wrong to imagine that the national government can become an important catalyst, motivator, and director of the system that will enhance its productivity – broadly understood. The important question, however, is how exactly it should practically do so? How can the central government develop a “strategic capacity” that can keep the widely distributed system as a whole moving towards improved performance with respect to both educational goals, and the wider economic, social, and political purposes that a polity hopes to advance through the provision of educational services. Answering that question for a broad class of national governments seeking to promoted sustained educational productivity relative to their goals is the task we will tackle in this essay (Moore and Spivack 2022).

Skin sampling is a diagnostic procedure based on analysis of extracted skin tissue and/or observation of biomarkers in bodily fluid. Sampling using microneedles (MNs) that minimize invasiveness are gaining attention over conventional biopsy/blood lancet. In this study, new MNs for electrochemically assisted skin sampling are reported, specifically tailored for combined skin tissue biopsy and interstitial fluid (ISF) extraction. To overcome risks associated with using metal MNs, a highly electroactive, mechanical flexible, and biocompatible organic conducting polymer (CP) coated onto plastic is chosen as an alternative. Two different variants of doped poly(3,4-ethylenedioxythiophene) are coated on polymethyl methacrylate and used in combination as a MN pair with subsequent testing via a variety of electrochemical techniques to (i) give real-time information of the MN penetration depth into the skin, and (ii) yield new information about the various salts present in the ISF. The MN skin sampler shows an ability to extract ions from the ISF when analyzed using X-ray photoelectron spectroscopy. This added chemical information in conjunction with existing biomarker analysis increases opportunity for disease/condition detection. For example, in the case of psoriasis information about the salt concentration in the skin is invaluable to combine with pathogenic gene expression for diagnosis. Refereed/Peer-reviewed

Low- and middle-income countries around the world face a profound educational challenge. At stake in meeting this challenge is their ability to participate effectively in an increasingly interdependent global economy, society, and polity, and to meet many other goals set out in the International Declaration of Human Rights. Turning the current challenge into an important opportunity will, by definition, require significant improvements in the productivity of national education systems. Productivity changes on this scale require innovations at all three levels of the national systems: micro (classroom pedagogy), meso (school and district management), and macro (national politics and policy) levels. This paper sets out principles for designing a process initiated and supported at the national level that can animate, guide, and evaluate the varied innovations that will help national government meet their educational goals along a path that supports their economic, social, and political goals as well.

An established one-dimensional Shelf Sea Physics and Primary Production (S2P3) model has been developed into three different new models: S2P3-NPZ which includes a nutrient–phytoplankton–zooplankton (NPZ) framework, where the grazing rate is no longer fixed but instead varies over time depending on different functions chosen to represent the predator–prey relationship between zooplankton and phytoplankton; S2P3-Photoacclim which includes a representation of the process of photo-acclimation and flexible stoichiometry in phytoplankton; and S2P3 v8.0 which combines the NPZ framework and the variable stoichiometry of phytoplankton at the same time. These model formulations are compared to buoy and conductivity–temperature–depth (CTD) observations, as well as zooplankton biomass and in situ phytoplankton physiological parameters obtained in the central Celtic Sea (CCS). Models were calibrated by comparison to observations of the timing and magnitude of the spring phytoplankton bloom, magnitude of the spring zooplankton bloom, and phytoplankton physiological parameters obtained throughout the water column. A sensitivity study was also performed for each model to understand the effects of individual parameters on model dynamics. Results demonstrate that better agreement with biological observations can be obtained through the addition of representations of photo-acclimation, flexible stoichiometry, and grazing provided these can be adequately constrained.

The high-latitude oceans are key areas of carbon and heat exchange between the atmosphere and the ocean. As such, they are a focus of both modern oceanographic and palaeoclimate research. However, most palaeoclimate proxies that could provide a long-term perspective are based on calcareous organisms, such as foraminifera, that are scarce or entirely absent in deep-sea sediments south of 50∘ S in the Southern Ocean and north of 40∘ N in the North Pacific. As a result, proxies need to be developed for the opal-based organisms (e.g. diatoms) found at these high latitudes, which dominate the biogenic sediments recovered from these regions. Here we present a method for the analysis of the boron (B) content and isotopic composition (δ11B) of diatom opal. We apply it for the first time to evaluate the relationship between seawater pH, δ11B and B concentration ([B]) in the frustules of the diatom Thalassiosira weissflogii, cultured across a range of carbon dioxide partial pressure (pCO2) and pH values. In agreement with existing data, we find that the [B] of the cultured diatom frustules increases with increasing pH (Mejía et al., 2013). δ11B shows a relatively well defined negative trend with increasing pH, completely distinct from any other biomineral previously measured. This relationship not only has implications for the magnitude of the isotopic fractionation that occurs during boron incorporation into opal, but also allows us to explore the potential of the boron-based proxies for palaeo-pH and palaeo-CO2 reconstruction in high-latitude marine sediments that have, up until now, eluded study due to the lack of suitable carbonate material.

Temperature and nutrient supply are key factors that control phytoplankton ecophysiology, but their role is commonly investigated in isolation. Their combined effect on resource allocation, photosynthetic strategy, and metabolism remains poorly understood. To characterize the photosynthetic strategy and resource allocation under different conditions, we analyzed the responses of a marine cyanobacterium (Synechococcus PCC 7002) to multiple combinations of temperature and nutrient supply. We measured the abundance of proteins involved in the dark (RuBisCO, rbcL) and light (Photosystem II, psbA) photosynthetic reactions, the content of chlorophyll a, carbon and nitrogen, and the rates of photosynthesis, respiration, and growth. We found that rbcL and psbA abundance increased with nutrient supply, whereas a temperature-induced increase in psbA occurred only in nutrient-replete treatments. Low temperature and abundant nutrients caused increased RuBisCO abundance, a pattern we observed also in natural phytoplankton assemblages across a wide latitudinal range. Photosynthesis and respiration increased with temperature only under nutrient-sufficient conditions. These results suggest that nutrient supply exerts a stronger effect than temperature upon both photosynthetic protein abundance and metabolic rates in Synechococcus sp. and that the temperature effect on photosynthetic physiology and metabolism is nutrient dependent. The preferential resource allocation into the light instead of the dark reactions of photosynthesis as temperature rises is likely related to the different temperature dependence of dark-reaction enzymatic rates versus photochemistry. These findings contribute to our understanding of the strategies for photosynthetic energy allocation in phytoplankton inhabiting contrasting environments.

Objective To evaluate a method of measuring the change in palatal length and shape following maxillary advancement using synchronous lateral videofluoroscopy and voice recording in order to understand how movement of the maxilla may affect VPI risk in patients with cleft lip and/or palate (CL/P). Design Retrospective cohort study of children with cleft lip and/or palate. Setting Single center, tertiary children's hospital. Participants Patients with cleft lip and/or palate who underwent maxillary advancement between 2016–21 inclusive. Interventions Maxillary advancement surgery, including those who underwent concurrent mandibular procedures. Main outcome measures The length of the soft palate and the genu angle were measured throughout palatal dynamic range. Pre- and post-operative measurements were compared using a one sided T-test, with subgroup analysis for patients with clinical VPI. Results Ten patients were examined. The mean distance of maxillary advancement was 10.5 mm. The average increase in pre-genu soft palate length was 2.8 mm in the resting position and 2.9 mm in the closed position. The genu angle decreased in the closed position by 16.3 degrees. Conclusions The soft palate showed limited ability to lengthen following maxillary advancement and this may explain the risk of VPI. There was partial compensation by the muscle sling of the palate as demonstrated by a more acute post-operative genu angle and this suggests one reason for the variability of VPI reported. Future research is required to investigate how length and shape changes measured using this method can predict VPI risk.

Photosynthesis holds the promise of sustainable generation of useful products using light energy. Key to realizing this potential is the ability to rationally design photosynthesis to redirect energy and reductant derived from photons to desired products. Cytochrome P450s (P450s), which catalyze a broad array of reactions, have been engineered into a variety of photosynthetic organisms, where their activity has been shown to be photosynthesis-dependent, thus acting as heterologous sinks of electrons derived from photosynthesis. Furthermore, the addition of P450s can increase the photosynthetic capacity of the host organism. In this study, we developed this technology further using a P450 (CYP1A1) expressed in the cyanobacterium Synechococcus sp. PCC 7002. We show that rationally engineering photosynthesis by the removal of a competing electron sink, the respiratory terminal oxidase cytochrome c oxidase, increased the activity of CYP1A1. We provide evidence that this enhanced CYP1A1 activity was facilitated via an increase in the flux of electrons through Photosystem I. We also conducted a transcriptomic analysis on the designed strains to gain a more holistic understanding of how the cell responds to rational engineering. We describe a complex response including changes in expression of genes involved in photosynthesis and electron transfer linked to respiration. Specifically, the expression of CYP1A1 resulted in the reduction in expression of other natural electron dissipation pathways. This study emphasizes the potential for engineering photosynthetic organisms in biotechnology but also highlights the need to consider the broader impacts on cellular metabolism of any rationally induced changes.

This study examined if participants respond to different types of suggestions, including hypnosis, uniquely or similarly. This study used 9 suggestibility measures and hypothesized a 3-factor model...

Flooding poses a serious public health hazard throughout the world. Flood modeling is an important tool for emergency preparedness and response, but some common methods require a high degree of expertise or may be unworkable due to poor data quality or data availability issues. The conceptually simple method of inverse distance weight modeling offers an alternative. Using stream gauges as inputs, this study interpolated stream elevation via inverse distance weight modeling under 15 different model input parameter scenarios for Harris County, Texas, USA, from August 25th to September 15th, 2017 (before, during, and after Hurricane Harvey inundated the county). A digital elevation model was used to identify areas where modeled stream elevation exceeded ground elevation, indicating flooding. Imagery and observed high water marks were used to validate the models' outputs. There was a high degree of agreement (between 79 and 88%) between imagery and model outputs of parameterizations visually validated. Quantitative validations based on high water marks were also positive, with a Nash-Sutcliffe efficiency of in excess of .6 for all parameterizations relative to a Nash-Sutcliffe efficiency of the benchmark of 0.56. Inverse distance weight modeling offers a simple, accurate method for first-order estimations of riverine flooding in near real-time using readily available data, and outputs are robust to some alterations to input parameters.

We present dissolved and total dissolvable trace elements for spring and summer cruises in 2010 in the high‐latitude North Atlantic. Surface and full depth data are provided for Al, Cd, Co, Cu, Mn, Ni, Pb, and Zn in the Iceland and Irminger Basins, and consequences of biological uptake and inputs by the spring Eyjafjallajökull volcanic eruption are assessed. Ash from Eyjafjallajökull resulted in pronounced increases in Al, Mn, and Zn in surface waters in close proximity to Iceland during the eruption, while 3 months later during the summer cruise levels had returned to more typical values for the region. The apparent seasonal removal ratios of surface trace elements were consistent with biological export. Assessment of supply of trace elements to the surface mixed layer for the region, excluding volcanic inputs, indicated that deep winter mixing was the dominant source, with diffusive mixing being a minor source (between 13.5% [dissolved Cd, DCd] and −2.43% [DZn] of deep winter flux), and atmospheric inputs being an important source only for DAl and DZn (DAl up to 42% and DZn up to 4.2% of deep winter + diffusive fluxes) and typically less than 1% for the other elements. Elemental supply ratios to the surface mixed layer through convection were comparable to apparent removal ratios we calculated between spring and summer. Given that deep mixing dominated nutrient and trace element supply to surface waters, predicted increases in water column stratification in this region may reduce supply, with potential consequences for primary production and the biological carbon pump., Key Points: Bio‐essential element concentrations in surface waters decreased from spring to summer with removal ratios reflecting biological uptake. Effects of volcanic inputs from Eyjafjallajökull in spring 2010 were pronounced for Al, Mn, and Zn but returned to typical levels in summer. Deep winter convection dominated trace element supply to surface waters with minor contributions from atmospheric and diffusive mixing., GEOMAR Helmholtz Centre for Ocean Research Kiel http://dx.doi.org/10.13039/501100003153, Natural Environment Research Council http://dx.doi.org/10.13039/501100000270

CD47 is widely expressed on the surface of cells. CD47 interacts with inhibitory receptor signaling protein alpha (SIRPα) to mediate a series of activities such as apoptosis, proliferation, and immune response. Tumor cells can escape the immune surveillance of macrophages through the CD47-SIRPa signaling pathway. Blocking CD47-SIRPα interactions has been shown to promote the destruction of cancer cells by phagocytes. Furthermore, there is growing evidence that targeting of the CD47-SIRPα axis may also promote antigen-presenting cell function. These identify the CD47-SIRPα axis as a promising innate immune checkpoint in cancer. We have generated humanized SIRPα and double humanized CD47/SIRPα mice model for drug efficacy and toxicity evaluation. The humanized mice with human extracellular domain and mouse cytoplasmic fragment of target protein showed similar immune cell population compared with wild type mice. The anti-CD47 antibody, Magrolimab (5F9) analog, displayed anti-tumor effect when administrated to humanized SIRPα mice bearing MC38-hCD47 (MC38 cells engineered to express human CD47) tumor cells. The tumor regression was also observed when treating humanized CD47/SIRPα mice bearing MC38-hCD47 with tested anti-CD47 antibody. Dual checkpoint blockade of CD47 and PD-L1 or PD1 have been reported as a synergistic therapy that activates both innate and adaptive immune response against tumors.We also generated humanized PD1/SIRPα and PD1/PDL1/SIRPα/CD47 mice model for efficacy and toxicity evaluation of drugs targeting for CD47/SIRPα-PD1/PD-L1 axes. Treatment with anti-CD47, anti-SIRPα and anti-PD-L1 alone showed tumor regression efficacy, and combination of anti-PD-L1 and anti-SIRPα or anti-CD47 showed improved anti-tumor effect compared with alone treatment. Those data suggested the humanized syngeneic mice model are useful for the efficacy evaluation of drugs targeting of axes.However, the administration of anti-CD47 blocking antibodies may cause haematotoxicity, including anaaemia and thrombocytopenia, because of the ubiquitous expression of CD47.In vitro Erythrocyte binding activity analysis showed that red blood cells(RBC) collected from humanized CD47/SIRPα mice could bind with Magrolimab analog, while another anti-CD47 antibody has low affinity with RBC. Furthermore, treatment with Magrolimab analog in CD47/SIRPα humanized mice caused haemagglutination and Hemolysis of human RBCs, which were not observed when treating with tested anti-CD47 antibody. Thus, the humanized CD47 and double humanized CD47/SIRPα mice are also suitable for CD47 antibody toxicity evaluation. In conclusion, humanized CD47/SIRPα and quadruple humanized PD1/PDL1/SIRPα/CD47 mice model provide a validated preclinical mouse model to interrogate new therapeutic agents targeting SIRPα-PD1 axes in immune oncology therapy. Citation Format: Juan Liang, Cunxiang Ju, Song Li, Weiwei Yu, Hongyan Sun, Santi Suryani Chen, Jing Zhao, Xiang Gao, Mark Moore. Humanized mice model for efficacy and toxicity evaluation of drugs targeting CD47-SIRPα-PD1-PD-L1 axes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 607.

Increasing influence of Atlantic water in the Arctic Ocean has the potential to significantly impact regional water temperature and salinity. Here we use a rDNA barcoding approach to reveal how microbial communities are partitioned into distinct assemblages across a gradient of Atlantic-Polar Water influence in the Norwegian Sea. Data suggest that temperate adapted bacteria may replace cold water taxa under a future scenario of increasing Atlantic influence, but the eukaryote response is more complex. Some abundant eukaryotic cold water taxa could persist, while less abundant eukaryotic taxa may be replaced by warmer adapted temperate species. Furthermore, within lineages, different taxa display evidence of increased relative abundance in reaction to favourable conditions and we observed that rare microbial taxa are sample site rather than region specific. Our findings have significant implications for the vulnerability of polar associated community assemblages, which may change, impacting the ecosystem services they provide, under predicted increases of Atlantic mixing and warming within the Arctic region.

Introduction The internet has improved access to knowledge, with a reported 72% of internet users accessing health information online. YouTube is the most popular video-sharing website and is a frequently accessed source for health information. There are concerns, however, that patients and carers may be unable to identify and filter for trustworthy sources of information on these platforms. This study aimed to assess the quality of videos that are likely to be accessed when families search YouTube for transcranial procedures for the management of craniosynostosis. Methodology This was a cross-sectional, observational study that evaluated YouTube videos when searching for “fronto-orbital advancement” or “cranial vault remodeling.” The first 25 videos for each term were included. Videos were assessed for quality using the previously validated JAMA and DISCERN scoring tools. Results There was low interobserver variability for the scoring tools used. There was no statistically significant correlation between the video quality and any video characteristics assessed. Videos published by organizations had higher mean quality scores for both the JAMA and DISCERN tools when compared to surgeon, patient, or medical device company-produced videos. Conclusion This study showed that searching YouTube for fronto-orbital advancement and cranial vault remodeling yields videos of low quality and therefore patients and carers should be discouraged from “YouTube-ing” these procedures. Platforms such as YouTube may provide an opportunity for craniofacial units to create and disseminate high-quality educational videos to complement routine perioperative education.