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Intrauterine growth restriction (IUGR) is a pregnancy complication impairing fetal growth and development. The compromised development is often attributed to disruptions of oxygen and nutrient supply from the placenta, resulting in a number of unfavourable physiological outcomes with impaired brain and organ growth. IUGR is associated with compromised development of both grey and white matter, predisposing the infant to adverse neurodevelopmental outcomes, including long‐lasting cognitive and motor difficulties. Cerebral thyroid hormone (TH) signalling, which plays a crucial role in regulating white and grey matter development, is dysregulated in IUGR, potentially contributing to the neurodevelopmental delays associated with this condition. Notably, one of the major TH transporters, monocarboxylate transporter‐8 (MCT8), is deficient in the fetal IUGR brain. Currently, no effective treatment to prevent or reverse IUGR exists. Management strategies involve close antenatal monitoring, management of maternal risk factors if present and early delivery if IUGR is found to be severe or worsening in utero. The overall goal is to determine the most appropriate time for delivery, balancing the risks of preterm birth with further fetal compromise due to IUGR. Drug candidates have shown either adverse effects or little to no benefits in this vulnerable population, urging further preclinical and clinical investigation to establish effective therapies. In this review, we discuss the major neuropathology of IUGR driven by uteroplacental insufficiency and the concomitant long‐term neurobehavioural impairments in individuals born IUGR. Importantly, we review the existing clinical and preclinical literature on cerebral TH signalling deficits, particularly the impaired expression of MCT8 and their correlation with IUGR. Lastly, we discuss the current evidence on MCT8‐independent TH analogues which mimic the brain actions of THs by being metabolised in a similar manner as promising, albeit underappreciated approaches to promote grey and white matter development and improve the neurobehavioural outcomes following IUGR. [ABSTRACT FROM AUTHOR]

This study uses ERA5 close‐proximity soundings and associated convective parameters to characterize significant tornadic storm (F/EF2+) environments between 1980 and 2020 in parts of Canada. It is shown that ERA5 convective parameters are suitable to represent observed parameters, based on radiosonde comparisons. Results indicate that the eastern Canadian Prairies have nearly double the lifted condensation level with higher level of free convection compared to eastern Canada (southern Ontario/Quebec). Eastern Canada has more a humid boundary layer and free troposphere that can lead to warmer cold pools, favoring tornadogenesis. Central Canada (Manitoba) has the largest mixed‐layer (ML) convective available potential energy (CAPE) mainly due to a combination of regional differences in low level moisture and steeper mid‐level lapse rates in western Canada. Central continental U.S. and Canadian regions appear to have the highest (most negative) convective inhibition, leading to more explosive initiation. Mean bulk wind shear and storm relative helicity (SRH) increases from west to east, with eastern regions being significantly larger. The supercell composite and significant tornado parameters are generally less than U.S. magnitudes, particularly in western Canada, and would require recalibration for more practical use in Canada. Overall, western Canada significant tornadic storms are associated with more low‐level looping hodographs and dominated by thermodynamic influences compared to larger wind influences in eastern regions. This is likely due to more spring, late summer, and autumn events that typically have well‐developed synoptic systems (stronger wind shear) with overall less buoyant energy in eastern regions. Plain Language Summary: This study identifies the meteorological conditions associated with strong tornadoes in parts of Canada with brief comparisons to other regions of the World. The main findings suggest that western Canada (Prairies) events are more dominated by the thermodynamic environment compared to eastern Canada that has more wind shear. Western regions tend to have more wind direction changes in the lower atmosphere compared to eastern regions. These differences may partially be due to eastern regions having more events in spring and autumn, where large scale weather systems tend to be more developed but with less thermal instability. All of these results suggest that strong tornadoes can occur in various environments within Canada, particularly similar to the U.S., however, some commonly used tornado forecasting indices may require recalibration to suit western Canadian environments. Key Points: Strong tornado environments in western Canada are more influenced by thermodynamics versus stronger wind shear in eastern CanadaSCP and STP parameters require recalibration for western Canada, likely through wind shear term adjustmentsThe six Canadian regions identified have statistically different strong tornado environments, given the convective parameters used [ABSTRACT FROM AUTHOR]

Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome. Synopsis: The SARS-CoV-2 NSP3 protein binds directly to fragile X mental retardation proteins (FMRPs) to support viral replication. NSP3 binding disrupts FMRP interaction with the stress granule protein UBAP2L, thereby preventing FMRP localization to these structures. The SARS-CoV-2 NSP3 protein binds to the KH domains of FMRPs through a short peptide motif. Engineered SARS-CoV-2 viruses unable to bind FMRPs have reduced replication. NSP3 binding to FMRPs disrupts their localization to stress granules through competition with UBAP2L. The SARS-CoV-2 NSP3 protein binds directly to fragile X mental retardation proteins (FMRPs) to support viral replication. NSP3 binding disrupts FMRP interaction with the stress granule protein UBAP2L, thereby preventing FMRP localization to these structures. [ABSTRACT FROM AUTHOR]

Introduction: Overactive bladder (OAB) can adversely affect health‐related quality‐of‐life (HRQoL) and adherence to treatments; however, the extent of their association is unknown. This study sought to characterize Sleep Disturbance, Depression, Fatigue, and patient‐reported medication adherence among adults with OAB in the United States. Materials and Methods: In this descriptive, observational study, patients completed patient‐reported outcome (PRO) measures of urinary symptoms, anxiety, depression, fatigue, sleep quality, and medication adherence. PRO scores were compared across age, sex, body mass index, and sleep and antidepressant medication‐taking subgroups. Exploratory analyses compared PRO scores between groups and estimated the effect size of differences. Results: Of 1013 patients contacted, 159 completed the assessments (female: 67.3%; ≥65 years of age: 53.5%; most severe OAB symptom: nocturia). Scale scores for Sleep Disturbance, Fatigue, and Depression were consistent with US population norms. No correlations of moderate or greater magnitude were observed between the severity of lower urinary tract symptoms and Sleep Disturbance, Fatigue, or Depression. When comparing individuals receiving antidepressants with those who were not, almost all outcomes including urinary symptoms, anxiety, and depression were significantly worse. Patients taking antidepressants also had poorer adherence to their OAB medications. Conclusion: In this cohort of individuals with OAB, Sleep Disturbance, Fatigue, and Depression scores were in line with general population reference values; however, among the subgroups analyzed, patients on antidepressants had worse HRQoL and more substantial impacts on medication adherence, highlighting the importance of the assessment and management of depression in this population. [ABSTRACT FROM AUTHOR]

Herein, it is reported that how a layer of samarium (Sm) with a thickness equivalent to ≈2 atoms (0.8 nm) deposited by thermal evaporation is remarkably effective at passivating polycrystalline copper (Cu) toward oxidation in ambient air. To monitor the rate of Cu oxidation in real time, slablike Cu films with a thickness of 9 nm are fabricated on glass modified with a layer of 3‐mercaptopropyl silatrane, which immobilizes condensing Cu atoms by reaction with the thiol moiety, promoting slablike film formation at very low thickness. Upon exposure to ambient air the rate of increase in electrical resistance due to reaction with oxygen and water is slowed by more than an order of magnitude when the Cu film is capped with the ultrathin Sm layer. After 1 year, the resistance increases by ≈30% as compared to ≈190% for Cu films without an ultrathin Sm layer. Photoelectron spectroscopy, atomic force microscopy, and Kelvin probe measurements shed light on the underlying mechanism of passivation. Additionally, the ultrathin Sm layer is greatly lowering the work function of polycrystalline Cu films making this approach attractive for applications requiring a low‐work‐function electrode with high stability in air. [ABSTRACT FROM AUTHOR]

Introduction: In 2020, almost half of all Clinical Commissioning Groups in England were restricting the number of higher cost drugs (HCDs) that could be prescribed for Rheumatoid Arthritis (RA) before an Individual Funding Request was required. We were interested in qualitatively exploring the experiences of prescribers affected by these restrictions and the experiences of patients who required four or more of these drugs. Methods: Semi‐structured interviews were conducted with five prescribers in restricted areas and six patients from our own service who had received four or more HCDs. The interviews were analysed thematically. Results: Prescribers reported feeling distressed and frustrated by the unsatisfactory service they were constrained to provide. Some prescribers continued partially effective treatments in order not to run out of options. They did not find Individual Funding Requests or the Blueteq High Cost Drug (HCD) System helpful in the management of these patients. The Blueteq HCD System is an electronic platform that allows health managers to monitor the prescribing of high‐cost medicines and manage the complexities associated with their use. Patients expressed severe distress at the prospect of running out of options and anxiety around the process of gaining approval for their next treatment. Conclusions: Restricting drugs for RA by the number which can be prescribed results in persistence with partially effective treatments, which is unsatisfactory for prescribers and patients, further it does not save money. Patients need to travel in their journey with RA and be able to try the next drug even though they know that it may not work. [ABSTRACT FROM AUTHOR]

Land cover classification is one of the most common applications of remote sensing and is used for developing and modifying land management policies on agricultural landscapes to achieve conservation and economic goals, such as reducing grassland degradation and improving livestock and crop production. In this study, the grassland classification of the crown lands (public grasslands in Canada) from a newly developed remotely sensed dataset in the Prairie Province of Manitoba (i.e., the Manitoba Grassland Inventory, MGI) was assessed in terms of accuracy by comparison to non‐spatial government records. The analysis consisted of (i) converting non‐spatial records from the provincial crown land database to spatially‐defined parcels by performing parcel delineations using geographic information system (GIS) and R programming tools, (ii) summarising the MGI classification at the same spatial scale, and (iii) comparing the agreement between MGI and the crown land database. The most common land cover types identified were: forest (30%) and shrubland (25%), followed by native (10%) and tame (9%) grasslands. However, the class agreements between woody (i.e., forests and shrublands) and grassy (i.e., native and tame grasslands) vegetation classes were low between these datasets because of their spectral similarities. Based on these results, we suggest additional refinements on both sensor and ground data to improve the classification agreement between these datasets. This study is one of the first attempts to compare ground‐collected government records against a remotely sensed product in Manitoba. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a complex obstetric issue describing a fetus that does not reach its genetic growth potential. The primary cause of FGR is placental dysfunction resulting in chronic fetal hypoxaemia, which in turn causes altered neurological, cardiovascular and respiratory development, some of which may be pathophysiological, particularly for neonatal life. The brainstem is the critical site of cardiovascular, respiratory and autonomic control, but there is little information describing how chronic hypoxaemia and the resulting FGR may affect brainstem neurodevelopment. This review provides an overview of the brainstem‐specific consequences of acute and chronic hypoxia, and what is known in FGR. In addition, we discuss how brainstem structural alterations may impair functional control of the cardiovascular and respiratory systems. Finally, we highlight the clinical and translational findings of the potential roles of the brainstem in maintaining cardiorespiratory adaptation in the transition from fetal to neonatal life under normal conditions and in response to the pathological environment that arises during development in growth‐restricted infants. This review emphasises the crucial role that the brainstem plays in mediating cardiovascular and respiratory responses during fetal and neonatal life. We assess whether chronic fetal hypoxaemia might alter structure and function of the brainstem, but this also serves to highlight knowledge gaps regarding FGR and brainstem development. [ABSTRACT FROM AUTHOR]

Magnetic and electronic properties of quantum materials heavily rely on the crystal structure even in the same chemical compositions. In this study, it is demonstrated that a layered tetragonal EuCd2Sb2 structure can be obtained by treating bulk trigonal EuCd2Sb2 under high pressure (6 GPa) and high temperature (600 °C). Magnetization measurements of the newly formed layered tetragonal EuCd2Sb2 confirm an antiferromagnetic ordering with Neel temperature (TN) around 16 K, which is significantly higher than that (TN ≈ 7 K) of trigonal EuCd2Sb2, consistent with heat capacity measurements. Moreover, bad metal behavior is observed in the temperature dependence of the electrical resistivity and the resistivity shows a dramatic increase around the Neel temperature. Electronic structure calculations with local density approximation dynamic mean–field theory (LDA+DMFT) show that this material is strongly correlated with well‐formed large magnetic moments, due to Hund's coupling, which is known to dramatically suppress the Kondo scale. [ABSTRACT FROM AUTHOR]

American popular and Electoral College presidential elections are forecast for 2020 and 2024, employing auto‐regressive time series and cross‐section probit models. Predictions are between the Republican and Democratic parties, not named persons. Year 2020: In July 2020, the Democrats' two party popular vote was predicted to be 52.7%. They received 52.2%. The cross‐section Electoral College model showed Democrats could not win the White House without winning all of Pennsylvania, Michigan, Wisconsin, and Nevada, which they did with 306 Electoral Votes. Year 2024: Democrats are predicted to win the 2024 presidency with 272 electoral votes, including Nevada's six votes and most of the large states they won in 2020. Democrats are predicted to win 53.7% of the popular vote. Fed's policies are expected to reduce inflation to 5.5%. Trump announced his candidacy in November 2022; however, other candidates are announcing for 2024. Trump's extreme positions in office and erratic behavior after losing in 2020 and then encouraging the January 6 insurrection are experiences Democrats can exploit. Events occurring after December 31, 2022, do not influence the predictions presented here. [ABSTRACT FROM AUTHOR]

An effective approach is reported to enhance the stability of inverted organo‐tin halide perovskite photovoltaics based on capping the cathode with a thin layer of bismuth. Using this simple approach, unencapsulated devices retain up to 70% of their peak power conversion efficiency after up to 100 h testing under continuous one sun solar illumination in ambient air and under electrical load, which is exceptional stability for an unencapsulated organo‐tin halide perovskite photovoltaic device tested in ambient air. The bismuth capping layer is shown to have two functions: First, it blocks corrosion of the metal cathode by iodine gas formed when those parts of the perovskite layer not protected by the cathode degrade. Second, it sequesters iodine gas by seeding its deposition on top of the bismuth capping layer, thereby keeping it away from the electro‐active parts of the device. The high affinity of iodine for bismuth is shown to correlate with the high polarizability of bismuth and the prevalence of the (012) crystal face at its surface. Bismuth is ideal for this purpose, because it is environmentally benign, non‐toxic, stable, cheap, and can be deposited by simple thermal evaporation at low temperature immediately after deposition of the cathode. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia is a common laboratory abnormality in dogs, and numerous diseases have been associated with its development. Estimates for the sensitivity and specificity of the degree of reduction of platelet concentration for the diagnosis of primary immune‐mediated thrombocytopenia (pITP) have not been reported. Objectives: To report the prevalence of different causes of thrombocytopenia in dogs in the United Kingdom and to investigate the utility of platelet concentration to differentiate causes of thrombocytopenia. Methods: Medical records of 762 dogs with thrombocytopenia presented to seven referral hospitals from January 2017 to December 2018 were retrospectively reviewed. Cases were assigned into the following categories: pITP, infectious diseases, neoplasia, inflammatory/other immune‐mediated disorders and miscellaneous causes. The prevalence of the different categories was estimated, and platelet concentrations were compared. Receiver‐operating characteristic (ROC) curves were used to investigate the utility of platelet concentration to differentiate between causes of thrombocytopenia. Results: The most common disease category associated with thrombocytopenia was neoplasia (27.3%), followed by miscellaneous causes (26.9%), pITP (18.8%), inflammatory/immune‐mediated disorders (14.4%) and infectious diseases (12.6%). Dogs with pITP had significantly lower platelet concentrations (median 8 × 109/L, range: 0–70 × 109/L) than dogs in the other four categories. Platelet concentration was useful for distinguishing pITP from other causes of thrombocytopenia (area under ROC curve = 0.89, 95% confidence interval 0.87, 0.92), with a platelet concentration ≤12 × 109/L being 60% sensitive and 90% specific. Conclusions: Severe thrombocytopenia was highly specific for a diagnosis of pITP, which was more prevalent in this UK population of thrombocytopenic dogs compared with previous epidemiological studies. Conversely, the proportion of dogs with infectious diseases was lower than in previous reports from other locations. [ABSTRACT FROM AUTHOR]

Background: Despite millions of COVID‐19 cases in the United States, it remains unknown whether a history of COVID‐19 infection impacts the safety of pharmacologic myocardial perfusion imaging stress testing (pharmacologic MPI). Hypothesis: The aim of this study was to assess if a prior COVID‐19 infection was associated with a higher risk of complications during and following pharmacologic MPI testing. Methods: This retrospective cohort analysis included 179 803 adults (≥18 years) from the PharMetrics® Plus claims database who underwent pharmacologic MPI between March 1, 2020 and February 28, 2021. Patients with a history of COVID‐19 infection (COVID‐19 group) were compared with propensity‐score matched no‐COVID‐19 history group for reversal agent use, 30‐day resource use, and post‐MPI cardiac events/procedures. Results: The most commonly used stress agent was regadenoson (91.7%). The COVID‐19 group (n = 6372; 3.5%) had slightly higher: reversal agent use (difference 1.13% [95% confidence interval [CI]: 0.33, 1.92]), all‐cause costs (difference USD $128 [95% CI: $73–$181]), and office visits (81.5% vs. 77.0%) than the no‐COVID‐19 group. Prior COVID‐19 infection did not appear to impact subsequent cardiac events/procedures. Conclusions: COVID‐19 history was associated with slightly higher reversal agent use, all‐cause costs, and office visits after pharmacologic MPI; however, the differences were not clinically meaningful. Concerns for use of stress agents in patients with prior COVID‐19 do not appear to be warranted. [ABSTRACT FROM AUTHOR]

SUMMARY: The soybean Rpp1 locus confers resistance to Phakopsora pachyrhizi, causal agent of rust, and resistance is usually dominant over susceptibility. However, dominance of Rpp1‐mediated resistance is lost when a resistant genotype (Rpp1 or Rpp1b) is crossed with susceptible line TMG06_0011, and the mechanism of this dominant susceptibility (DS) is unknown. Sequencing the Rpp1 region reveals that the TMG06_0011 Rpp1 locus has a single nucleotide‐binding site leucine‐rich repeat (NBS‐LRR) gene (DS‐R), whereas resistant PI 594760B (Rpp1b) is similar to PI 200492 (Rpp1) and has three NBS‐LRR resistance gene candidates. Evidence that DS‐R is the cause of DS was reflected in virus‐induced gene silencing of DS‐R in Rpp1b/DS‐R or Rpp1/DS‐R heterozygous plants with resistance partially restored. In heterozygous Rpp1b/DS‐R plants, expression of Rpp1b candidate genes was not significantly altered, indicating no effect of DS‐R on transcription. Physical interaction of the DS‐R protein with candidate Rpp1b resistance proteins was supported by yeast two‐hybrid studies and in silico modeling. Thus, we conclude that suppression of resistance most likely does not occur at the transcript level, but instead probably at the protein level, possibly with Rpp1 function inhibited by binding to the DS‐R protein. The DS‐R gene was found in other soybean lines, with an estimated allele frequency of 6% in a diverse population, and also found in wild soybean (Glycine soja). The identification of a dominant susceptible NBS‐LRR gene provides insight into the behavior of NBS‐LRR proteins and serves as a reminder to breeders that the dominance of an R gene can be influenced by a susceptibility allele. Significance Statement: Most resistance genes are inherited dominantly, although the present study serves as a reminder to breeders that the dominance of an R gene can be influenced by a susceptibility allele. The study identified a susceptible NBS‐LRR allele that can negate the dominance of the Rpp1‐mediated resistance to Asian soybean rust. The results support suppression of resistance occurring at the protein level, possibly through the interaction between the susceptible protein and the resistance protein. [ABSTRACT FROM AUTHOR]

Objective: Seizures are more common in the neonatal period than at any other stage of life. Phenobarbital is the first‐line treatment for neonatal seizures and is at best effective in approximately 50% of babies, but may contribute to neuronal injury. Here, we assessed the efficacy of phenobarbital versus the synthetic neurosteroid, ganaxolone, to moderate seizure activity and neuropathology in neonatal lambs exposed to perinatal asphyxia. Methods: Asphyxia was induced via umbilical cord occlusion in term lambs at birth. Lambs were treated with ganaxolone (5mg/kg/bolus then 5mg/kg/day for 2 days) or phenobarbital (20mg/kg/bolus then 5mg/kg/day for 2 days) at 6 hours. Abnormal brain activity was classified as stereotypic evolving (SE) seizures, epileptiform discharges (EDs), and epileptiform transients (ETs) using continuous amplitude‐integrated electroencephalographic recordings. At 48 hours, lambs were euthanized for brain pathology. Results: Asphyxia caused abnormal brain activity, including SE seizures that peaked at 18 to 20 hours, EDs, and ETs, and induced neuronal degeneration and neuroinflammation. Ganaxolone treatment was associated with an 86.4% reduction in the number of seizures compared to the asphyxia group. The total seizure duration in the asphyxia+ganaxolone group was less than the untreated asphyxia group. There was no difference in the number of SE seizures between the asphyxia and asphyxia+phenobarbital groups or duration of SE seizures. Ganaxolone treatment, but not phenobarbital, reduced neuronal degeneration within hippocampal CA1 and CA3 regions, and cortical neurons, and ganaxolone reduced neuroinflammation within the thalamus. Interpretation: Ganaxolone provided better seizure control than phenobarbital in this perinatal asphyxia model and was neuroprotective for the newborn brain, affording a new therapeutic opportunity for treatment of neonatal seizures. ANN NEUROL 2022;92:1066–1079 [ABSTRACT FROM AUTHOR]

Introduction: Overactive bladder (OAB) and frailty are independently associated with patient burden. However, economic burden and treatment‐taking behavior have not been well characterized among frail patients with OAB, which, given the varying safety and tolerability profiles of available treatments, is crucial. Objectives: To assess costs, health care resource utilization, treatment‐taking behavior (persistence and adherence) to OAB medication in older, frail OAB patients. Methods: This was a retrospective cohort study using international business machines MarketScan Medicare Supplemental claims data. Eligible frail patients (per Claims‐based Frailty Index score) initiating mirabegron were 1:2 propensity score matched (based on age, sex, and other characteristics) with those initiating antimuscarinics and were followed up to 1 year. All‐cause, per‐person, per‐month costs, health care encounters, persistence (median days to discontinuation assessed using Kaplan−Meier methods) and adherence (≥80% of proportion of days covered at Day 365) were compared. Results: From 2527 patients with incident mirabegron (21%) or antimuscarinic (79%) dispensations, 516 incident mirabegron users (median age: 82 years, 64% female) were matched to 1032 incident antimuscarinic users (median age: 81 years, 62% female). Median cost was higher in mirabegron group ($1581 vs. $1197 per month); this was primarily driven by medication cost. There was no difference in medical encounters. Adherence (39.1% vs. 33.8%) and persistence (103 vs. 90 days) were higher in mirabegron users. Conclusions: Among frail older adults with OAB, mirabegron use was associated with higher costs and potential improvements in treatment‐taking behaviors, particularly with respect to treatment adherence, versus those initiating antimuscarinics. [ABSTRACT FROM AUTHOR]

The well‐established importance of Agulhas Current "leakage" for Indian‐Atlantic Ocean exchange of heat and salt raises the question of the relevance of Agulhas eddies for carbon and nitrogen cycling. We measured net primary production (NPP), nitrate and ammonium uptake, and nitrification along a transect of the Cape Basin (CB) in winter 2017, including across an anticyclonic Agulhas eddy sampled at high‐resolution. Euphotic zone‐integrated rates of NPP and nitrogen uptake were more than three‐fold lower at the eddy center than at its edges, with intermediate rates measured outside the eddy. Additionally, proportionally more nitrate was consumed at the eddy edges than at its center. Mixed‐layer integrated nitrification rates were highest at the eddy‐center, with lower rates at the edges and in the surrounding basin. Accounting for phytoplankton consumption of newly nitrified nitrate in the eddy decreased the carbon export potential inferred from nitrate uptake (i.e., the f‐ratio) by 66% ± 37% (vs. a 14% ± 22% decrease across the rest of the transect). At most stations, NPP and total measured nitrogen uptake were decoupled relative to stoichiometric expectations, with roughly a third of NPP possibly supported by regenerated dissolved organic nitrogen (DON). Accounting for DON uptake decreased the average f‐ratio from 0.28 ± 0.26 to 0.22 ± 0.21, with the highest f‐ratio estimated for an eddy‐edge station (0.64) and the lowest for its center (0.00). While the low productivity metrics measured in the eddy‐center could imply that Agulhas leakage decreases carbon export potential in the CB, enhanced nutrient supply and consumption at eddy edges may (partly) offset this reduction. Plain Language Summary: Mesoscale eddies are abundant in the ocean, transporting physical, chemical, and biological properties from the eddy source region. Eddies can also cause small‐scale upwelling and/or downwelling, which affect the local biogeochemistry and biology (e.g., altering phytoplankton growth by changing the nutrient and/or light conditions). Large anticyclonic eddies that pinch off the Agulhas Current south of Africa transfer warm, salty waters from the Indian to the Atlantic Ocean, thereby playing a crucial role in ocean circulation. By contrast, little is known of the role of Agulhas eddies in carbon and nitrogen cycling. We find that the physical perturbations caused by the passage of an Agulhas eddy into the southeastern Atlantic stimulate primary production and nitrate uptake at the eddy edges, implying enhanced CO2 removal to depth, while productivity (and CO2 removal) is depressed at the eddy center. Additionally, the deep mixed layers created by the eddy's anticyclonic circulation favor high rates of nitrification, which produces recycled nitrate. Phytoplankton consumption of this nitrate yields no net removal of CO2, exacerbating the dampening effect of the eddy on Atlantic productivity. It is possible, however, that the reduction in productivity may be partly offset by the elevated supply and consumption of subsurface nutrients at the eddy edges. Key Points: Primary production and carbon export potential are elevated at Agulhas eddy edges and reduced at their centersAgulhas eddies host high rates of mixed‐layer nitrification that can supply 100% of phytoplankton nitrateDissolved organic nitrogen appears to fuel a significant fraction of primary production in Agulhas eddies and the Cape Basin [ABSTRACT FROM AUTHOR]

Prophylactic creatine treatment may reduce hypoxic brain injury due to its ability to sustain intracellular ATP levels thereby reducing oxidative and metabolic stress responses during oxygen deprivation. Using microdialysis, we investigated the real‐time in vivo effects of fetal creatine supplementation on cerebral metabolism following acute in utero hypoxia caused by umbilical cord occlusion (UCO). Fetal sheep (118 days' gestational age (dGA)) were implanted with an inflatable Silastic cuff around the umbilical cord and a microdialysis probe inserted into the right cerebral hemisphere for interstitial fluid sampling. Creatine (6 mg kg−1 h−1) or saline was continuously infused intravenously from 122 dGA. At 131 dGA, a 10 min UCO was induced. Hourly microdialysis samples were obtained from −24 to 72 h post‐UCO and analysed for percentage change of hydroxyl radicals (•OH) and interstitial metabolites (lactate, pyruvate, glutamate, glycerol, glycine). Histochemical markers of protein and lipid oxidation were assessed at post‐mortem 72 h post‐UCO. Prior to UCO, creatine treatment reduced pyruvate and glycerol concentrations in the microdialysate outflow. Creatine treatment reduced interstitial cerebral •OH outflow 0 to 24 h post‐UCO. Fetuses with higher arterial creatine concentrations before UCO presented with reduced levels of hypoxaemia (PO2${P_{{{\rm{O}}_{\rm{2}}}}}$ and SO2${S_{{{\rm{O}}_{\rm{2}}}}}$) during UCO which associated with reduced interstitial cerebral pyruvate, lactate and •OH accumulation. No effects of creatine treatment on immunohistochemical markers of oxidative stress were found. In conclusion, fetal creatine treatment decreased cerebral outflow of •OH and was associated with an improvement in cerebral bioenergetics following acute hypoxia. Key points: Fetal hypoxia can cause persistent metabolic and oxidative stress responses that disturb energy homeostasis in the brain. Creatine in its phosphorylated form is an endogenous phosphagen; therefore, supplementation is a proposed prophylactic treatment for fetal hypoxia.Fetal sheep instrumented with a cerebral microdialysis probe were continuously infused with or without creatine‐monohydrate for 10 days before induction of 10 min umbilical cord occlusion (UCO; 131 days' gestation). Cerebral interstitial fluid was collected up to 72 h following UCO.Prior to UCO, fetal creatine supplementation reduced interstitial cerebral pyruvate and glycerol concentrations.Fetal creatine supplementation reduced cerebral hydroxyl radical efflux up to 24 h post‐UCO. Fetuses with higher arterial creatine concentrations before UCO and reduced levels of systemic hypoxaemia during UCO were associated with reduced cerebral interstitial pyruvate, lactate and •OH following UCO.Creatine supplementation leads to some improvements in cerebral bioenergetics following in utero acute hypoxia. [ABSTRACT FROM AUTHOR]

Background: Current reports about the use of splenectomy for the management of immune‐mediated hemolytic anemia (IMHA) or immune‐mediated thrombocytopenia (ITP) or both in dogs are limited. Objectives: To retrospectively describe the use of splenectomy as part of the management for IMHA, ITP, and concurrent IMHA and severe thrombocytopenia (CIST) in dogs. It was hypothesized that splenectomy would be beneficial in allowing for reduction of dose of immunosuppressive drugs or discontinuation in 1 or more of these groups. Animals: Seventeen client‐owned dogs (7 with IMHA, 7 with ITP, and 3 with CIST) were identified across 7 UK‐based referral hospitals from a study period of 2005 to 2016. Methods: Data were collected retrospectively via questionnaires and included information about diagnosis, management and treatment response before and after splenectomy. Based on clinical outcome, treatment with splenectomy as part of the management protocol was classified as either successful or unsuccessful. Results: Six of 7 dogs with ITP were managed successfully with splenectomy as part of their management protocol (3 complete and 3 partial responses), although 1 subsequently developed suspected IMHA. Of the 7 dogs with IMHA, splenectomy was part of a successful management protocol in 4 dogs (2 complete and 2 partial responses). In the CIST group, 1 case (1/3) responded completely to management with splenectomy as part of the management protocol. Conclusions and Clinical Importance: Splenectomy was considered successful and well tolerated in most cases of isolated ITP. Whether there is a benefit of splenectomy in cases of IMHA and CIST could not be determined in the current study. [ABSTRACT FROM AUTHOR]

Objective: To understand the experience of rural Aboriginal and Torres Strait Islanders in engaging with oral health care services and programs in order to support the development of oral health services and prevention programs that better meet their needs. Design: The study used a qualitative research design, which aims to describe participants' lived experience of engaging with oral health services and prevention programs in a rural Aboriginal and Torres Strait Islander community. Focus group discussions and in‐depth interviews were conducted with 27 participants. The 15 transcribed discussions were analysed using a 6‐step phenomenological process. Setting: A rural community in Queensland, Australia, with a predominantly Aboriginal population. Participants: Participants were purposively recruited from established health and community groups. Main outcome: System‐level barriers to accessing and engaging with oral health services and prevention influence how communities manage oral health and seek treatment. Results: The study identified 4 main themes describing the community's experience: service location and the efforts required to access oral health services; the financial burden of accessing oral health care and practising prevention; lack of confidence in oral health services; and the avoidance or delaying of accessing care for dental problems. Results confirmed a high burden of oral disease but limited attendance at an oral health facility and difficulties engaging in preventative oral health behaviours. Treatment seeking was usually instigated by the experience of pain and typically at a tertiary health facility. Conclusion: Aboriginal and Torres Strait Islanders in rural communities experience a high burden of oral disease but have limited engagement with oral health services. This is associated with system‐level barriers to accessing and engaging with oral health services and prevention. [ABSTRACT FROM AUTHOR]

Drought management is currently informed by a variety of approaches, mostly responding to drought crisis when it happens. Toward more effective and integrated drought management, we introduce a conceptual drought diagnosis framework inspired by diagnostic concepts from the field of medicine. This framework comprises five steps: 1. Initial diagnostic assessment; 2. Diagnostic testing; 3. Consultation; 4. Communication of the diagnosis; and 5. Treatment and prognosis. To illustrate the need for the proposed approach, four case studies of recently drought‐affected regions were selected: the city of Cape Town, the state of California, the Northeast region of Brazil, and the Horn of Africa. Contrasting elements for these cases include the geographic extent and political boundaries, climate, socio‐economics, and the relevance of different water resources (e.g., rainfall, reservoirs, and aquifers). For each case, we identified documented practices and policies and reflected on them in terms of drought misdiagnosis or incomplete diagnosis that have aggravated socio‐economic and environmental drought impacts. A common example is the preference for technical solutions (e.g., installing infrastructure to augment water supply), rather than measures that reduce vulnerability. Analysis of these four drought case studies confirmed the anticipated need for a comprehensive approach to drought diagnosis for more successful treatment and prevention of drought. Using an analogy with medical science can be helpful toward comprehensively diagnosing droughts for a variety of contexts and assessing the effectiveness of proposed interventions. This framework can help drought managers to be more proactive in enabling drought‐affected regions to become more drought resilient in the future. Plain Language Summary: Droughts are becoming more common around the world, are occurring in new areas, lasting longer, and are affecting more people. When drought hits, we often experience water shortages, which can affect agriculture leading to food shortages. Additional drought impacts on health, lifestyle, and ecosystems include drying rivers and lakes, dust storms, water use restrictions, a lack of snow, dying forests, and wildfires. In extreme cases, droughts cause famine, disease, and migration. The fact that such drought impacts regularly make the news shows how ineffectively we currently manage drought; because the common practice is to respond to drought crisis as it happens rather than preparing in advance. Considering drought as a health disorder, we can follow the process used in medicine to diagnose that disorder and prescribe treatment. We suggest using this approach would enable us to identify where and how a location is vulnerable to drought and work on treatments. We could improve the health of a location before drought hits, thus reducing drought impacts. We discuss four recent drought cases: the city of Cape Town, state of California, Northeast region of Brazil, and Horn of Africa, to illustrate how drought could be better dealt with using our proposed approach. Key Points: Analysis of recent droughts shows that drought diagnosis is often insufficient leading to unsuccessful strategies to deal with droughtDrought diagnosis can be improved by using an analogy with the medical diagnostic processThis emphasizes that the focus of a comprehensive drought diagnosis should be to prescribe treatment that reduces drought impacts [ABSTRACT FROM AUTHOR]

Melanin‐like compounds have been studied in recent years for their electron transport and ultraviolet (UV) light absorbance properties as well as applications as functional, biocompatible catalysts, and material additives. Pyomelanin is a unique form of melanin compounds that has not received significant attention. Here, a strain of Yarrowia lipolytica suitable for the production of nearly 2.8 g L−1 of homogentisic acid (HGA) is metabolically engineered, which can then be oxidized to form pyomelanin either in situ or through altering pH. By using this biosourced material, a series of material traits including spectral analysis/UV–vis absorbance properties, electronic and metal interaction/chelation properties, and effectiveness in polymer dispersions with poly(l‐lactide) are evaluated. In all cases, biosourced pyomelanin performs on par with or better than a chemically sourced analog. In a performance application, it is explored how pyomelanin may be blended at low concentrations to increase the elasticity of a rigid commercial polymer. Collectively, this work establishes biosourced pyomelanin as a versatile compound for unique material applications. [ABSTRACT FROM AUTHOR]

Plagioclase ultraphyric basalts (PUBs) are a class of mid‐ocean ridge (MOR) lavas found in a variety of ocean floor environments, are characterized by abundant (15–40 volume %) plagioclase megacrysts and a diverse trace element and isotopic signature. Paradoxically, we never see lavas erupted on the seafloor that are in equilibrium with these PUB megacrysts. Based on petrographic evidence, melt inclusion composition, and new data on depth of entrapment calculated from CO2 contents in plagioclase‐hosted inclusions, many of the megacrysts formed at upper mantle pressures (∼3–7 kbars). To constrain the composition of the parent magmas of the plagioclase megacrysts, we conducted a series of experiments at 5 and 10 kbars using mid‐ocean ridge basalts glasses as starting materials. The experimental results were consistent with the presence of a pseudoazeotrope in the anorthitic segment of the plagioclase + basalt pseudobinary. This has the effect of dropping the anorthitic end of the feldspar loop, lowering the solidus for upper mantle conditions, and driving evolving magmas toward higher Ca. As magmas rise and pressure drops, the pseudoazeotrope disappears, and the feldspar loop at the high‐An end rises, causing those magmas to undergo decompression crystallization of plagioclase and resorption of olivine. Therefore, the conditions which generated the magmas from which the megacrysts form disappear as the magmas rise and magmas evolve toward lower Ca, Mg (as we normally assume during plagioclase + olivine crystallization). In effect, the phase equilibria conditions that allow for the generation of such liquids also prevent them from being erupted as lavas. Plain Language Summary: Much of our understanding of the Earth's mantle is based on study of the magmas erupted from the mid‐ocean ridge (MOR) system. This investigation involves a class of MOR lavas, plagioclase ultraphyric basalts (PUB), characterized by abundant anorthitic (high‐Ca) megacrysts. The question we address relates to the fact that few naturally occurring MOR lavas are in equilibrium with such anorthitic compositions. Understanding what the geochemical signal of the megacrysts means requires we understand what their parental magma types are. We conducted a series of experiments at mantle pressures on a pseudobinary in the plagioclase‐MOR liquid system. Our results document the presence of a thermal maximum (pseudoazeotrope) on the anorthitic end of the pseudobinary. The effect of this pseudoazeotrope is to lower (in temperature) the anorthitic end of the feldspar loop. Magmas evolving under those conditions evolve to higher Ca and lower Mg at depths above 15 km. As magmas rise, the feldspar loop at the high‐An end rises, causing those magmas to undergo decompression crystallization, preventing such liquids from being erupted on the seafloor. In effect, the conditions that generate the unique composition of anorthitic megacrysts prevent their parental liquids from being erupted on the ocean floor as lavas. Key Points: Our results document the presence of a thermal maximum (pseudoazeotrope) on the anorthitic end of the pseudobinaryThe conditions generate unique composition of anorthitic megacrysts prevent their parental liquids from being erupted on the ocean floorPhase equilibria at high P and change in high An plagioclase melting loop cause formation of magmas that form plagioclase megacrysts [ABSTRACT FROM AUTHOR]

Unencapsulated organo‐tin halide perovskite photovoltaic (PV) devices exhibiting record stability (for organo‐tin perovskite PV devices) when tested under continuous one sun solar illumination in ambient air and under electrical load are reported. This exceptional stability is made possible by the use of a bathocuproine | copper cathode in an inverted device architecture. A series of experiments designed to elucidate the underlying reasons for the high stability show that, compared to conventional silver electrodes, compact copper electrodes are far more resistant to corrosion by I2 gas (evolved when organo‐tin halide decomposes) and toward adverse morphological evolution and ingress of oxygen and water molecules through the top electrode into the device. The findings of these experiments show that copper should be the metal of choice for the reflective cathode in inverted tin perovskite PVs when the material interfacing the metal interacts strongly with it, enabling compact film formation and a stable interface toward copper diffusion into the adjacent charge transport layer. [ABSTRACT FROM AUTHOR]

The first determination of the phase diagram of the novel ferroelectric relaxor xBi(Zn2/3Nb1/3)O3–(1 − x)BaTiO3 (BZN‐BT) has been achieved with a combination of high‐resolution X‐ray and neutron diffraction up to the miscibility limit near x(BZN) = 20.0% over a temperature range 20 < T < 400 K. The combined X‐ray and neutron data show that the instability within the xBZN‐(1−x)BT system reaches a maximum at x = 3.9% and is driven by B‐site displacement and distortion of the oxygen octahedra in the polar phases. Composition‐dependent effects include a narrow Amm2‐dominated region focused at x = 3.9%, significant convergence of the lattice parameters in both P4mm and Amm2 phases, and sharp maxima in piezoelectric coefficient d33 and maximum polarization Pmax. Lattice parameter dilation at x ≥ 4.0% was observed for both P4mm and Amm2 unit cells, alongside the first appearance of Pm3m at 295 K and the onset of significant dielectric relaxation. Low‐temperature neutron diffraction indicated a weak or non‐existent temperature dependence on the transition from ferroelectric at x = 3.9% to ferroelectric relaxor at x = 4.0%. Temperature‐dependent phase transitions were eliminated near x = 3.0%, with the ferroelectric limit observed at x = 5.0% and a transition to a low‐loss relaxor dielectric near x = 8.0%. [ABSTRACT FROM AUTHOR]

The first determination of the phase diagram of the novel ferroelectric relaxor xBi(Zn2/3Nb1/3)O3–(1 − x)BaTiO3 (BZN‐BT) has been achieved with a combination of high‐resolution X‐ray and neutron diffraction up to the miscibility limit near x(BZN) = 20.0% over a temperature range 20 < T < 400 K. The combined X‐ray and neutron data show that the instability within the xBZN‐(1−x)BT system reaches a maximum at x = 3.9% and is driven by B‐site displacement and distortion of the oxygen octahedra in the polar phases. Composition‐dependent effects include a narrow Amm2‐dominated region focused at x = 3.9%, significant convergence of the lattice parameters in both P4mm and Amm2 phases, and sharp maxima in piezoelectric coefficient d33 and maximum polarization Pmax. Lattice parameter dilation at x ≥ 4.0% was observed for both P4mm and Amm2 unit cells, alongside the first appearance of Pm3m at 295 K and the onset of significant dielectric relaxation. Low‐temperature neutron diffraction indicated a weak or non‐existent temperature dependence on the transition from ferroelectric at x = 3.9% to ferroelectric relaxor at x = 4.0%. Temperature‐dependent phase transitions were eliminated near x = 3.0%, with the ferroelectric limit observed at x = 5.0% and a transition to a low‐loss relaxor dielectric near x = 8.0%. [ABSTRACT FROM AUTHOR]

Background: Prior to commencing methotrexate, patients routinely attend an education consultation with a rheumatology nurse. The purpose of the consultation is to discuss the patients' expectations and concerns related to commencing methotrexate, the benefits of treatment, potential side effects and monitoring requirements. The aim of this study was to use video analysis to assess the structure, content and mode of delivery of the consultation. Methods: Video recordings of 10 patient–nurse consultations, involving four specialist rheumatology nurses, were analysed and transcribed. The consultations were compared with the Calgary–Cambridge (CC) consultation model. Transcripts were thematically analysed. Data were quantitatively assessed for verbal and non‐verbal behaviours. Findings: Assessment of the video data using the CC model demonstrated good structure, content and flow of the consultation, influenced by the use of an information leaflet. Consultations generally consisted of communication from nurse to patient rather than a dialogue; the nurse spoke for 69%–86% of the time; clarification of the patient's understanding of the information did not take place in any of the consultations. Thematic analysis also showed that the nurse agenda dominated and the nurse was aware of 'overloading' the patient with information. Cues from the patients to discuss items of importance were often missed. Conclusion: Video analysis can be used to identify the aspects of the consultation that work well and those areas of the consultation that could be improved with specific training. [ABSTRACT FROM AUTHOR]

Objectives: To comparatively evaluate a low‐cost otoscope with a traditional device among health care workers in Malawi. Methods: The study is a prospective, comparative, qualitative observational survey of health care worker's opinions using 5‐point Likert rating scales and tick box categories in a 10‐item survey questionnaire. Twenty‐five mixed cadre health care workers from the Ear, Nose, and Throat Department of the Queen Elizabeth Hospital, Blantyre in Malawi were recruited. Outcomes measures used were ease of speculum attachment, handling, insertion, stability, the quality of view, color, build, brightness, overall ease of use, and their suitability for local work. Results: The low‐cost otoscope scored statistically higher in overall combined performance, as well as in the remaining four out of the nine attributes. Notably, 54.2% of users rated the low‐cost device more suitable than the traditional device for use in low‐middle income countries, 25% were equivocal, and 20.8% preferred the traditional device. Conclusion: This study found the Arclight otoscope to be an appropriate and practical substitute for more expensive traditional otoscopes for the delivery of ENT services in low resource settings. Level of Evidence: N/A [ABSTRACT FROM AUTHOR]

Key points: Brief episodes of severe fetal hypoxia can arise in late gestation as a result of interruption of normal umbilical blood flowSystemic parameters and blood chemistry indicate complete recovery within 1–2 hours, although the long‐term effects on fetal brain functions are unknownFetal sheep were subjected to umbilical cord occlusion (UCO) for 10 min at 131 days of gestation, and then monitored intensively until onset of labour or delivery (<145 days of gestation)Normal patterns of fetal behaviour, including breathing movements, episodes of high and low voltage electorcortical activity, eye movements and postural (neck) muscle activity, were disrupted for 3–10 days after the UCOPreterm labour and delivery occurred in a significant number of the pregnancies after UCO compared to the control (sham‐UCO) cohort. Complications arising from antepartum events such as impaired umbilical blood flow can cause significant fetal hypoxia. These complications can be unpredictable, as well as difficult to detect, and thus we lack a detailed understanding of the (patho)physiological changes that occur between the antenatal in utero event and birth. In the present study, we assessed the consequences of brief (∼10 min) umbilical cord occlusion (UCO) in fetal sheep at ∼0.88 gestation on fetal plasma cortisol concentrations and fetal behaviour [electrocortical (EcoG), electo‐oculargram (EOG), nuchal muscle electromyography (EMG) and breathing activities] in the days following UCO. UCO caused a rapid onset of fetal hypoxaemia, hypercapnia, and acidosis; however, by 6 h, all blood parameters and cardiovascular status were normalized and not different from the control (Sham‐UCO) cohort. Subsequently, the incidence of fetal breathing movements decreased compared to the control group, and abnormal behavioural patterns developed over the days following UCO and leading up to the onset of labour, which included increased high voltage and sub‐low voltage ECoG and EOG activities, as well as decreased nuchal EMG activity. Fetuses subjected to UCO went into labour 7.9 ± 3.6 days post‐UCO (139.5 ± 3.2 days of gestation) compared to the control group fetuses at 13.6 ± 3.3 days post‐sham UCO (144 ± 2.2 days of gestation; P < 0.05), despite comparable increases in fetal plasma cortisol and a similar body weight at birth. Thus, a single transient episode of complete UCO late in gestation in fetal sheep can result in prolonged effects on fetal brain activity and premature labour, suggesting persisting effects on fetal cerebral metabolism. Key points: Brief episodes of severe fetal hypoxia can arise in late gestation as a result of interruption of normal umbilical blood flowSystemic parameters and blood chemistry indicate complete recovery within 1–2 hours, although the long‐term effects on fetal brain functions are unknownFetal sheep were subjected to umbilical cord occlusion (UCO) for 10 min at 131 days of gestation, and then monitored intensively until onset of labour or delivery (<145 days of gestation)Normal patterns of fetal behaviour, including breathing movements, episodes of high and low voltage electorcortical activity, eye movements and postural (neck) muscle activity, were disrupted for 3–10 days after the UCOPreterm labour and delivery occurred in a significant number of the pregnancies after UCO compared to the control (sham‐UCO) cohort. [ABSTRACT FROM AUTHOR]

Background: Serum bile acids (SBAs) are frequently measured in dogs. However, there is limited data comparing SBAs in different liver diseases diagnosed according to standardized histological criteria. Objectives: To compare resting and postprandial SBAs, and determine their sensitivity and specificity, for various liver diseases in dogs. Animals Three hundred and forty‐one client‐owned dogs with suspected liver disease that had a liver biopsy and SBAs measured. Methods: Multicenter retrospective study. Cases were classified according to standardized histological criteria. The sensitivity and specificity of resting and postprandial SBAs for the diagnosis of each liver disease, and all liver diseases combined, were calculated. Results: The median resting SBAs were highest in dogs with cirrhosis (98.8 μmol/L; range, 6‐135) and congenital circulatory anomalies (CCa; 79.45 μmol/L; 0.3‐705). The highest median postprandial concentrations were found in CCa (126 μmol/L; 0‐726) and chronic hepatitis (CH; 54.3 μmol/L; 0‐260). Using the cut‐off value of 10 μmol/L, the highest sensitivities of resting SBAs were recorded in dogs with CCa (87.5%; 95% confidence interval, 76.8‐94.4) and CH (81.1%; 71.5‐88.6). The sensitivities of postprandial SBAs were the highest in cholangitis (100%; 47.8‐100.0) and CCa (91.1%; 78.8‐97.5). The specificities of resting and postprandial SBAs for all diseases were 49.3% (37.6‐61.1) and 29.7% (15.9‐47.0), respectively. Conclusions and Clinical Importance: Postprandial SBAs are more sensitive but less specific than resting SBAs for the diagnosis of liver disease. There were dogs in all categories of liver disease with resting SBAs <10 and >90 μmol/L. Therefore, careful interpretation of both normal and elevated values is required. [ABSTRACT FROM AUTHOR]

Citizen science is proliferating in the water sciences with increasing public involvement in monitoring water resources, climate variables, water quality, and in mapping and modeling exercises. In addition to the well‐reported scientific benefits of such projects, in particular solving data scarcity issues, it is common to extol the benefits for participants, for example, increased knowledge and empowerment. We reviewed 549 publications concerning citizen science applications in the water sciences to examine personal benefits and motivations, and wider community benefits. The potential benefits of involvement were often simply listed without explanation or investigation. Studies that investigated whether or not participants and communities actually benefitted from involvement, or experienced negative impacts, were uncommon, especially in the Global South. Assuming certain benefits will be experienced can be fallacious as in some cases the intended benefits were either not achieved or in fact had negative impacts. Identified benefits are described and we reveal that more consideration should be given to how these benefits interrelate and how they build community capitals to foster their realization in citizen science water projects. Additionally, we describe identified negative impacts showing they were seldom considered though they may not be uncommon and should be borne in mind when implementing citizen science. Given the time and effort commitment made by citizen scientists for the benefit of research, there is a need for further study of participants and communities involved in citizen science applications to water, particularly in low‐income regions, to ensure both researchers and communities are benefitting. This article is categorized under:Human Water > Human Water [ABSTRACT FROM AUTHOR]

Single‐crystal X‐ray diffraction structures of the 5‐amino‐2‐methylpyridinium hydrogen fumarate salt have been solved at 150 and 300 K (CCDC 1952142 and 1952143). A base–acid–base–acid ring is formed through pyridinium‐carboxylate and amine‐carboxylate hydrogen bonds that hold together chains formed from hydrogen‐bonded hydrogen fumarate ions. 1H and 13C chemical shifts as well as 14N shifts that additionally depend on the quadrupolar interaction are determined by experimental magic angle spinning (MAS) solid‐state nuclear magnetic resonance (NMR) and gauge‐including projector‐augmented wave (GIPAW) calculation. Two‐dimensional homonuclear 1H‐1H double‐quantum (DQ) MAS and heteronuclear 1H‐13C and 14N‐1H spectra are presented. Only small differences of up to 0.1 and 0.6 ppm for 1H and 13C are observed between GIPAW calculations starting with the two structures solved at 150 and 300 K (after geometry optimisation of atomic positions, but not unit cell parameters). A comparison of GIPAW‐calculated 1H chemical shifts for isolated molecules and the full crystal structures is indicative of hydrogen bonding strength. [ABSTRACT FROM AUTHOR]

Development of durable resistance to soybean rust (SBR) is challenging due to the pathogenic diversity of Phakopsora pachyrhizi populations. The objective of this research was to investigate and confirm the genomic locations of Rpp genes in the Ugandan line UG‐5 that confer resistance to different SBR pathotypes. Bulked segregant analysis revealed two genomic regions associated with resistance in a cross with rust‐susceptible 'Williams 82'. Composite interval mapping in the F2 and F2:3 populations had a LOD score of 48.7 in a region 0.38 cM away from the estimated location of the Rpp1 locus on chromosome (Chr.) 18. An approximately 23‐Kbp interval spanning the Rpp1 locus was flanked by SNP markers ss715632313 and ss715632318. Another interval was identified at the Rpp3 locus on Chr. 6 between markers Satt100 and ss715594488 (2.4 cM) in the F2 population and between Satt100 and ss715594874 (4.3 cM) in the F2:3 population, with a maximum LOD score of 25.6. UG‐5 was thus confirmed to have SBR resistance genes at the Rpp1 and Rpp3 loci that can be pyramided into other elite cultivars. [ABSTRACT FROM AUTHOR]

Osteomalacia is a condition where bone mineralisation is impaired by lack of vitamin D. It more commonly affects darker skinned individuals in the UK, especially if they wear occlusive clothing. Lifestyle changes and Vitamin D supplementation are recommended for those people most at risk through these factors, but such advice is not commonly followed. This indicates an educational need for information on osteomalacia and its treatment. Using a previously developed Mind‐Map on osteomalacia, a layered and interactive" PowerPoint" style presentation was developed, using hyperlinks. The "basic" layer was translated into Urdu and validated by Urdu speaking professionals. The translation was accurate and meaningful and the tool was well received by representatives of the community. The tool was used to educate a group of 10 community leaders from the Urdu community in Stourbridge, UK. Knowledge about osteomalacia was tested in these people, before and after the education, and increased from an average of 14 to 25 points (p < 0.05). Qualitative feedback gained was very positive. Conclusion: An interactive educational tool for Osteomalacia was developed and translated into Urdu. Use of the tool resulted in increased knowledge about osteomalacia. [ABSTRACT FROM AUTHOR]

The accelerated growth of aquaculture has caused environmental impacts in many countries. Examples include the use of large volumes of water, discharge of effluents with high nutrient content, the occupation of large areas, natural habitat alternation and the escape of exotic species. Biofloc technology (BFT) is an aquaculture tool that requires minimal water exchange, promotes the nutrient recycling optimizing resources and produces natural food in situ by forming suspended microbial aggregates in the water (bioflocs). These microorganisms provide multiple benefits such as water quality control, pathogen resistance and nutritional supplementation. Species such as Litopenaeus vannamei and tilapia have been successfully applied in BFT. In addition, there are also an increasing number of studies focused on alternative species with promising results. This paper describes essential aspects of biofloc technology, its application in aquaculture and the potential to extend its benefits to new aquaculture species such as Chilean river shrimp Cryphiops caementarius. This paper describes the future challenges of this technology as well as opportunities for its application. [ABSTRACT FROM AUTHOR]

Aims: To characterize the epidemiology and treatment patterns of adult men (≥40 years) diagnosed with, or treated for, overactive bladder (OAB) and/or benign prostatic hyperplasia (BPH). Methods: This retrospective observational study used data extracted from the IBM MarketScan Commercial Claims and Encounters database and the Medicare Supplemental Coordination of Benefits database. Men with BPH and/or OAB were identified and observed to assess treatment and diagnostic patterns. Results: Within the entire study sample (N = 462 400), BPH diagnosis (61.5%) and BPH treatment (73.7%) were more common than the corresponding values for OAB (25.8% and 7.0%, respectively). Notably, among diagnosed individuals, the dispensation of a corresponding treatment was more likely in individuals diagnosed with BPH (183 672 out of 284 416 = 64.6%) compared with OAB (16 468 out of 119 236 = 13.8%). Among newly diagnosed and/or treated patients (n = 196 576), only 60.3% received treatment. Among treated patients, most experienced only a single type of treatment (93.4%), 6.6% went on to receive a secondary treatment and 3.5% a tertiary. The most common primary treatment was alpha‐blocker monotherapy (76.9%) followed by tadalafil monotherapy (16.4%). Among those untreated at first diagnosis, the median time between diagnosis and treatment initiation was 128 days. Conclusions: Diagnosis and management of OAB among males are challenging given the inherent overlap in symptoms observed with BPH. Unsurprisingly, we found that BPH is diagnosed and treated more frequently than OAB; but the differences between diagnosis and treatment patterns for the two conditions highlight the potential undertreatment of OAB and misdirection of therapy for men with a combination of voiding and storage symptoms. [ABSTRACT FROM AUTHOR]

Synchrotron X‐ray diffraction (XRD) measured on the XMaS beamline at the ESRF was used to characterize the alloy composition and crystalline surface corrosion of three copper alloy Tudor artefacts recovered from the undersea wreck of King Henry VIII's warship the Mary Rose. The XRD method adopted has a dynamic range ∼1:105 and allows reflections <0.002% of the height of major reflections in the pattern to be discerned above the background without smoothing. Laboratory XRD, scanning electron microscopy–energy dispersive spectroscopy, synchrotron X‐ray fluorescence and X‐ray excited optical luminescence–X‐ray near‐edge absorption structure were used as supporting techniques, and the combination revealed structural and compositional features of importance to both archaeology and conservation. The artefacts were brass links believed to be fragments of chainmail and were excavated from the seabed during 1981 and 1982. Their condition reflects very different treatment just after recovery, viz. complete cleaning and conservation, chemical corrosion inhibition and chloride removal only, and distilled water soaking only (to remove the chlorides). The brass composition has been determined for all three at least in the top 7 µm or so as Cu(73%)Zn(27%) from the lattice constant. Measurement of the peak widths showed significant differences in the crystallite size and microstrain between the three samples. All of the links are found to be almost chloride‐free with the main corrosion products being spertiniite, sphalerite, zincite, covellite and chalcocite. The balance of corrosion products between the links reflects the conservation treatment applied to one and points to different corrosion environments for the other two. [ABSTRACT FROM AUTHOR]

Background: Glomerular filtration rate (GFR) estimation is the gold standard for assessment of renal function, although the clinical utility of this test is unclear. Objectives: To describe the clinical utility of GFR estimation in dogs. Animals: Medical records of 132 dogs that had serum iohexol clearance measured between 2012 and 2017. Methods: Iohexol clearance and clinical records were reviewed and submitting practices contacted to obtain outcome data. Dogs were classified into 4 groups based on the reason for performing GFR estimation: A1 (screening for pre‐azotemic chronic kidney disease [CKD], n = 105), A2 (confirmation of azotemic CKD, n = 3), B (screening for pre‐azotemic acute kidney injury, n = 19), and C (miscellaneous causes, n = 5). Descriptive review of the clinical utility of GFR estimation is provided. Results: For dogs in Group A1, renal disease was diagnosed in 9/9 dogs with a GFR ≥40% decreased below the mean GFR of their body weight category, in 5/6 dogs with a ≥30% but <40% reduction in GFR and in 7/9 dogs with a ≥20% but <30% reduction in GFR. Conclusions and Clinical Importance: Glomerular filtration rate estimation is useful for the diagnosis of CKD before the onset of azotemia. [ABSTRACT FROM AUTHOR]

Objectives: Clinical response to antibody‐based immunotherapies targeting checkpoint inhibitors is critically dependent on the tumor immune microenvironment (TIME). However, the precise impact of the TIME on adoptive cellular immunotherapy remains unexplored. Here we have conducted a long‐term follow‐up analysis of patients with recurrent glioblastoma multiforme (GBM) who were treated with autologous CMV‐specific T‐cell therapy to delineate the potential impact of the TIME on their clinical response. Methods: Multiplexed immunohistochemical analysis of CD3, PD‐L1 and Sox‐2 in GBM tissue biopsies obtained before autologous T‐cell therapy was carried out and correlated with long‐term survival of GBM patients adoptively treated with T‐cell therapy. Results: Tumor microenvironment analyses revealed that the pre‐treatment cellular composition of the tumor tissue may influence the subsequent response to adoptive T‐cell therapy. GBM patients who showed prolonged overall survival following T‐cell therapy had a significantly lower number of tumor‐infiltrating CD3+ T cells in recurrent tumors than that in patients with short‐term survival. Furthermore, long‐term surviving patients showed low or undetectable PD‐L1 expression in tumor cells in recurrent GBM biopsies. Conclusion: We hypothesise that lack of PD‐L1‐mediated immunosuppression in the TIME may allow efficient immune control following adoptive T‐cell therapy. Future studies combining anti‐PD‐L1 or genetically modified T cells with PD‐1 receptor knockdown could be considered to improve clinical responses in patients who have high PD‐L1 expression in their tumors. [ABSTRACT FROM AUTHOR]

The article discusses a study to examine the recurrence and mortality within the T1 and T2 glottic cancer cohort at a tertiary referral head and neck center in Great Britain. Topics discussed include disease recurrence throughout the five¿year follow¿up period in the cohort of T1 and T2 glottic cancer patients, T1 glottic squamous cell carcinomas, and the likelihood of recurrence in T2 versus T1 tumors.

Although most recharge estimation studies apply multiple methods to identify the possible range in recharge values, many do not distinguish clearly enough between inherent uncertainty of the methods and other factors affecting the results. We investigated the additional value that can be gained from multi‐method recharge studies through insights into hydrogeological understanding, in addition to characterizing uncertainty. Nine separate groundwater recharge estimation methods, with a total of 17 variations, were applied at a shallow aquifer in northwest Ethiopia in the context of the potential for shallow groundwater resource development. These gave a wide range of recharge values from 45 to 814 mm/a. Critical assessment indicated that the results depended on what the recharge represents (actual, potential, minimum recharge or change in aquifer storage), and spatial and temporal scales, as well as uncertainties from application of each method. Important insights into the hydrogeological system were gained from this detailed analysis, which also confirmed that the range of values for actual recharge was reduced to around 280‐430 mm/a. This study demonstrates that even when assumptions behind methods are violated, as they often are to some degree especially when data are limited, valuable insights into the hydrogeological system can be gained from application of multiple methods. Article impact statement: Analysis of common recharge methods shows the value of extracting additional information to improve hydrogeological understanding. [ABSTRACT FROM AUTHOR]