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This article assesses the individual and joint impact of pressure, temperature, and relative humidity on the accuracy of atmospheric CO2 measurements collected by unmanned aerial systems (UASs) using low-cost commercial non-dispersive infrared (NDIR) sensors. We build upon previous experimental results in the literature and present a new dataset with increased gradients for each environmental variable to match the abrupt changes found in UAS-based atmospheric vertical profiles. As a key contribution, we present a low-complexity correction procedure to mitigate the impact of these variables and reduce errors in this type of atmospheric CO2 measurement. Our findings support the use of low-cost NDIR sensors for UAS-based atmospheric CO2 measurements as a complementary in situ tool for many scientific applications.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.

This article aims to utilize an adapted version of Trentham's Inverse Consistency Protocol (ICP) as a way in which any ecclesial organization can act productively when confronted with seemingly controversial paradigms such as social emotional learning (SEL). The ICP can help Christian leaders discern potential areas of inconsistency or affirm authentic congruence with an organization's faith tradition. Tenets from the Collaborative for Academic, Social, and Emotional Learning (CASEL) were submitted through the four-step protocol. Findings suggest that CASEL is a valuable framework when applied authentically and that ICP is a constructive tool for engaging in the social sciences with integrity.

A sample of 496 early childhood teachers was assigned randomly in two phases to a series of professional development (PD) interventions. Phase I intervention was a 14-week course on effective teacher-child interactions. Participants were then re-randomized into Phase II intervention, which consisted of individual, interactions-focused coaching. Impacts of the course, coaching, and their combination were evaluated relative to business-as-usual controls on knowledge of effective interactions, skill in detecting effective interactions, observed teacher-child interactions, beliefs about intentional teaching, and children's classroom engagement. "Research Findings:" Teachers exposed to the course demonstrated greater knowledge of and skills in detecting effective teacher child-interactions, and displayed higher quality instructional support in their interactions with children during the year following the course. Teachers who received coaching were also observed to display higher levels of instructional support and children in their classrooms displayed more positive engagement with adults. However, neither teachers nor children appeared to gain additional benefit from the combination of the course and coaching. "Practice or Policy:" The results have important implications for efforts to systematically and efficiently improve the quality of early childhood programs through the delivery of PD that is directly aligned with teachers' classroom interactions.

Today's teachers face intense stress (Robinson et al. in School Mental Health 15(1):78-89, 2023), which means they often need to regulate strong emotions, like frustration and anxiety, in the classroom. Given the importance of this skill for classroom life, it is essential that we gain a more nuanced understanding of teachers' emotion regulation (ER). The teacher ER literature is growing, and we aim to contribute meaningfully in three ways. First, we examine two general ER strategies (cognitive reappraisal and expressive suppression) descriptively in a sample of 190 public school teachers (grades K-6) from 33 elementary schools. Second, we explore whether these two ER strategies are correlated with important teacher (burnout, years of experience) and classroom (class size) factors. Third, we examine whether these ER strategies are linked to observed emotionally supportive classroom interactions. Teachers in this sample reported frequent use of cognitive reappraisal and relatively infrequent use of expressive suppression in general. These two ER strategies were not significantly correlated with one another. Teachers reporting greater use of cognitive reappraisal reported less burnout, while teachers reporting greater use of expressive suppression reported more burnout. Teachers with more years of experience also reported greater use of cognitive reappraisal. Contrary to our hypotheses, cognitive reappraisal and expressive suppression were not related to class size and did not predict unique variance in observed emotionally supportive interactions. Implications for teacher supports and interventions are discussed.

Abstract Wind wave observations in shallow coastal waters are essential for calibrating, validating, and improving numerical wave models to predict sediment transport, shoreline change, and coastal hazards such as beach erosion and oceanic inundation. Although ocean buoys and satellites provide near-global coverage of deep-water wave conditions, shallow-water wave observations remain sparse and often inaccessible. Nearshore wave conditions may vary considerably alongshore due to coastline orientation and shape, bathymetry and islands. We present a growing dataset of in-situ wave buoy observations from shallow waters (

The beach–foredune system at Bengello Beach has been monitored monthly to bimonthly at four profiles (P1–P4) since 1972 and documented the building of a foredune. This paper addresses the remarkable changes which occurred in 2022 as storm waves overtopped and trimmed this foredune at all profiles, then later removed this entire feature at two of the profiles (P3, P4) but not the others (P1, P2). Wave parameters for these storm events, measured by deepwater and nearshore wave buoys, enable a comparison of storm characteristics and resulting beach–foredune impact. During the storm event which destroyed the foredune, nearshore wave height exceeded deepwater wave height, in contrast with other storms that year. The beach–foredune lost 78 m3/m in 2022 and the notable 1974 storms that impacted this coastline resulted in 95 m3/m volume loss. During 2023, beach recovery has occurred, but not rebuilt the foredune. It had persisted for ~40 years enduring many other severe storm events, and the coastal protection afforded by the dune system has been compromised. This highlights the need to consider dune morphology in assessments of erosion hazard and inundation risk along similar coastlines.

Social housing for dairy calves has a range of benefits for social development, yet there is limited understanding of how social bonds form early in life. We characterized effects of early life social contact on the development of social preference for calves varying in familiarity. A total of 40 calves were tested in a social preference test at 4 weeks of age to assess the formation of social bonds and preference for their peers. Within an open-field social preference test, focal calves were presented with two stimulus calves, one ‘more familiar’ and one ‘less familiar’. We found that pair-housed calves spent more time in close proximity with either stimulus calf and had a greater preference for their pen-mate, compared to another calf reared within visual contact. Individually housed calves exhibited no preference for calves reared within visual but not physical contact compared to calves that were completely unfamiliar. Of the calves that approached both stimulus calves, individually housed calves that approached the ‘less familiar’ calf first spent less time near the ‘more familiar’ calf, whereas behavior of pair-housed calves was not affected by the first calf approached. These results suggest that physical contact is necessary for the development of social bonds in young dairy calves, and early life social housing may support the development of normal social behavior in dairy cattle.

Soil physical parameter calculation by inverse modelling provides an indirect way of estimating the unsaturated hydraulic properties of soils. However many measurements are needed to provide sufficient data to determine unknown parameters. The objective of this research was to assess the use of unsaturated water flow and solute transport experiments, in horizontal packed soil columns, to estimate the parameters that govern water flow and solute transport. The derived parameters are then used to predict water infiltration and solute migration in a repacked soil wedge. Horizontal columns packed with Red Ferrosol were used in a nitrate diffusion experiment to estimate either three or six parameters of the van Genuchten–Mualem equation while keeping residual and saturated water content, and saturated hydraulic conductivity fixed to independently measured values. These parameters were calculated using the inverse optimisation routines in Hydrus 1D. Nitrate concentrations measured along the horizontal soil columns were used to independently determine the Langmuir adsorption isotherm. The soil hydraulic properties described by the van Genuchten–Mualem equation, and the NO3– adsorption isotherm, were then used to predict water and NO3– distributions from a point-source in two 3D flow scenarios. The use of horizontal columns of repacked soil and inverse modelling to quantify the soil water retention curve was found to be a simple and effective method for determining soil hydraulic properties of Red Ferrosols. These generated parameters supported subsequent testing of interactive flow and reactive transport processes under dynamic flow conditions.

Soils treated with lime-amended biosolids (LAB), poppy seed waste (PSW), anaerobically digested biosolids (ADB) and poppy mulch (PM) and incubated at 12.5°C for 56 days released 45%, 36%, 25%, and −8%, respectively, of total applied N as plant available nitrogen (PAN) by the end of the incubation. The mineralisation rates were contrary to expectations based on the C : N ratios of the four products: LAB (5 : 1), PSW (7 : 1), ADB (3 : 1), and PM (16 : 1). PM showed a significant negative priming effect over the incubation period. These results have implications for production agriculture in temperate regions where application and incorporation of bio-resources traditionally occurs in autumn and spring when soil and air temperatures are relatively low. Current application times may not be suitable for nitrogen release to satisfy crop demand.

Development-perched watertables and subsurface lateral flows in texture-contrast soils (duplex) are commonly believed to occur as a consequence of the hydraulic discontinuity between the A and B soil horizons. However, in catchments containing shallow bedrock, subsurface lateral flows result from a combination of preferential flow from the soil surface to the soil—bedrock interface, undulations in the bedrock topography, lateral flow through macropore networks at the soil—bedrock interface, and the influence of antecedent soil moisture on macropore connectivity. Review of literature indicates that some of these processes may also be involved in the development of subsurface lateral flow in texture contrast soils. However, the extent to which these mechanisms can be applied to texture contrast soils requires further field studies. Improved process understanding is required for modelling subsurface lateral flows in order to improve the management of waterlogging, drainage, salinity, and offsite agrochemicals movement.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has increased markedly with the introduction of population-based mammographic screening. DCIS is usually diagnosed non-operatively. Although sentinel lymph node biopsy (SNB) has become the standard of care for patients with invasive breast carcinoma, its use in patients with DCIS is controversial. AIM: To examine the justification for offering SNB at the time of primary surgery to patients with a needle core biopsy (NCB) diagnosis of DCIS. METHODS: A retrospective analysis was performed of 145 patients with an NCB diagnosis of DCIS who had SNB performed at the time of primary surgery. The study focused on rates of SNB positivity and underestimation of invasive carcinoma by NCB, and sought to identify factors that might predict the presence of invasive carcinoma in the excision specimen. RESULTS: 7/145 patients (4.8%) had a positive sentinel lymph node, four macrometastases and three micrometastases. 6/7 patients had invasive carcinoma in the final excision specimen. 55/145 patients (37.9%) with an NCB diagnosis of DCIS had invasive carcinoma in the excision specimen. The median invasive tumour size was 6 mm. A radiological mass and areas of invasion <1 mm, amounting to "at least microinvasion" on NCB were predictive of invasive carcinoma in the excision specimen. CONCLUSIONS: SNB positivity in pure DCIS is rare. In view of the high rate of underestimation of invasive carcinoma in patients with an NCB diagnosis of DCIS in this study, SNB appears justified in this group of patients. [ABSTRACT FROM AUTHOR]

AbstractSome supplementary results and interpretations on the theory of Hall MHD solitons (McKenzie and Doyle 2002 Phys. Plasmas9, 55) are presented. It is shown that the Hall MHD soliton reduces, in the appropriate limit, to an electrostatic ion?cyclotron soliton. It is also shown how the dynamical equations governing the Hall MHD soliton can be obtained from a Hamiltonian H. Soliton solutions correspond to H= 0, periodic solutions to H0. Possible applications are discussed. A non-canonical Hamiltonian picture is developed and compared to the well-known example of a free rigid body. [ABSTRACT FROM AUTHOR]

Higher education institutions must recognize the responsibility to support online adult learners as members of a larger global community and technological advancements have made this a reality. COVID-19 restrictions to in-person learning highlighted the need for online learning platforms that promote the benefits of teacher presence, consider the tenets of the Community of Inquiry model, and commit to the principles of andragogy. A need to explore the possibilities for fostering global citizenship among adult learners in online higher education environments has been identified as a problem space and a methodological approach will be used to connect findings from the literature with best practices for practitioners. Global citizenship is not a new concept; however, current and worldwide events have created a renewed dedication to the construct. Discussions based on the literature and established theoretical frameworks will precede practical implications for directors, course designers, and instructors. Online education will be described as ripe with opportunities for higher education institutions to foster global citizenship among adult learners.

ABSTRACT: Objectives: Whole genome and transcriptome analysis of 213 Pseudomonas aeruginosa isolates resistant to antipseudomonal β-lactams collected in 30 countries was performed to evaluate resistance mechanisms against these agents. Methods: Isolates were susceptibility tested by reference broth microdilution. Whole genome and transcriptome sequencing were performed, and data were analysed using open-source tools. A statistical analysis of changes in the expression of >5500 genes was compared to the expression of PAO1. Results: The high-risk clones ST235 and ST111 were the most prevalent among >90 sequence types (STs). Metallo-β-lactamase (MBLs) genes were detected in 40 isolates. AmpC and MexXY were the most common genes overexpressed in approximately 50% of the 173 isolates that did not carry MBLs. Isolates overexpressing pmrA and pmrB, the norspermidine production genes speD2 and speE2, and the operon arnBCADTEF-ugd were noted among strains resistant to ceftolozane-tazobactam and ceftazidime-avibactam, despite the lack of polymyxin resistance often associated to increased expression of these genes. Overexpression of MuxABC-OpmB, OprG, and OprE proteins were associated with resistance to ceftolozane-tazobactam in addition to the usual genes involved in cephalosporin, monobactam, and carbapenem resistance. Statistical analysis identified discrete mutations in ArmZ, OprD, and AmpC that correlated to antipseudomonal β-lactam resistance. Conclusions: P. aeruginosa resistance mechanisms are complex. This analysis suggests the role of multiple genes in resistance to antipseudomonal β-lactams, including some not commonly described.

ABSTRACT To evaluate the resistance mechanisms among Pseudomonas aeruginosa clinical isolates exhibiting meropenem (MEM) MIC values higher than meropenem-vaborbactam (MEV). P. aeruginosa clinical isolates collected in US hospitals from 2014 to 2019 were susceptibility tested. Whole-genome and transcriptome sequencing were performed. Results were analyzed for strain typing, acquired β-lactamases, and mutations in chromosomal genes; gene expression was measured for known β-lactam resistance contributors. Results were compared to a control group of 10 P. aeruginosa isolates displaying MIC values at 8 mg/L for meropenem ± vaborbactam (MEM = MEV). Out of 88 isolates displaying MEM > MEV, 33 (37.5%) isolates had reproducibly lower MIC values for meropenem-vaborbactam compared to meropenem when retested. The expression of mexX, mexY, mexZ, and ampC was significantly greater among a higher percentage of the MEM > MEV isolates. Furthermore, the association of mexXY and ampC overexpression was detected in 17/33 MEM > MEV isolates and only 1/10 MEM = MEV isolate. In addition, the Pseudomonas-derived cephalosporinase amino acid substitution R79Q was detected among 33.3% of the isolates displaying MEM > MEV, and none of the isolates displayed MEM = MEV. Other resistance mechanisms were not observed or were equally observed in both groups. In rare cases, vaborbactam plays a role in lowering the meropenem MIC values in P. aeruginosa clinical isolates likely due to the inhibition of the AmpC gene that was overexpressed in the presence of upregulation of MexXY with or without alterations in the AmpC gene. IMPORTANCE Pseudomonas aeruginosa isolates are intrinsically resistant to multiple antimicrobial agents and meropenem is an important therapeutic option to treat infections caused by this organism. Meropenem-vaborbactam activity is similar to that of meropenem alone against P. aeruginosa isolates. Isolates belonging to this species that display lower meropenem-vaborbactam compared to meropenem are rare. We initiated this study to understand the resistance mechanisms that could lead to lower meropenem-vaborbactam MIC values when compared to meropenem alone. We documented that isolates displaying lower meropenem-vaborbactam exhibited overexpression of MexXY and AmpC. In addition, isolates displaying the R79Q PDC (AmpC) mutation were more likely to display lower meropenem-vaborbactam when compared to isolates displaying the same MIC values for these agents.

Abstract Background Ischemic stroke provokes a neuroinflammatory response and simultaneously promotes release of epinephrine and norepinephrine by the sympathetic nervous system. This increased sympathetic outflow can act on β2-adrenergic receptors expressed by immune cells such as brain-resident microglia and monocyte-derived macrophages (MDMs), but the effect on post-stroke neuroinflammation is unknown. Thus, we investigated how changes in β2-adrenergic signaling after stroke onset influence the microglia/MDM stroke response, and the specific importance of microglia/MDM β2-adrenergic receptors to post-stroke neuroinflammation. Methods To investigate the effects of β2-adrenergic receptor manipulation on post-stroke neuroinflammation, we administered the β2-adrenergic receptor agonist clenbuterol to mice 3 h after the onset of photothrombotic stroke. We immunostained to quantify microglia/MDM numbers and proliferation and to assess morphology and activation 3 days later. We assessed stroke outcomes by measuring infarct volume and functional motor recovery and analyzed gene expression levels of neuroinflammatory molecules. Finally, we evaluated changes in cytokine expression and microglia/MDM response in brains of mice with selective knockout of the β2-adrenergic receptor from microglia and monocyte-lineage cells. Results We report that clenbuterol treatment after stroke onset causes enlarged microglia/MDMs and impairs their proliferation, resulting in reduced numbers of these cells in the peri-infarct cortex by 1.7-fold at 3 days after stroke. These changes in microglia/MDMs were associated with increased infarct volume in clenbuterol-treated animals. In mice that had the β2-adrenergic receptor specifically knocked out of microglia/MDMs, there was no change in morphology or numbers of these cells after stroke. However, knockdown of β2-adrenergic receptors in microglia and MDMs resulted in increased expression of TNFα and IL-10 in peri-infarct tissue, while stimulation of β2-adrenergic receptors with clenbuterol had the opposite effect, suppressing TNFα and IL-10 expression. Conclusions We identified β2-adrenergic receptor signaling as an important regulator of the neuroimmune response after ischemic stroke. Increased β2-adrenergic signaling after stroke onset generally suppressed the microglia/MDM response, reducing upregulation of both pro- and anti-inflammatory cytokines, and increasing stroke size. In contrast, diminished β2-adrenergic signaling in microglia/MDMs augmented both pro- and anti-inflammatory cytokine expression after stroke. The β2-adrenergic receptor may therefore present a therapeutic target for improving the post-stroke neuroinflammatory and repair process.

Background. Several studies have shown that obese patients undergoing liver transplantation (LT) have an increased risk of mortality regardless of Model of End Stage Liver Disease (MELD) scores. The purpose of this study is to identify the range of body mass index (BMI) at LT associated with the lowest risks of posttransplant mortality by MELD category. Methods. A retrospective cohort of patients aged 18 years or older from the Organ Procurement and Transplantation Network database undergoing LT between February 27, 2002, and December 31, 2013, was identified and followed up through March 14, 2014. Patients' MELD score at the time of transplantation was categorized into 10 or lower (MELD1), 11 to 18 (MELD2), 19 to 24 (MELD3), and 25 or higher (MELD4). Multivariable adjusted Cox proportional hazard analyses were conducted. Results. Among 48 226 patients in the analytic cohort (14.8% were in MELD1, 33.7% were in MELD2, 19.6% were in MELD3, and 32.0% were in MELD4), 25% died with mean follow-up of 1371 days. For MELD1, patient BMI ranging from 30 to 33 was associated with a better survival outcome than BMI less than 30 or 33 or greater; for MELD2, BMI ranging from 28 to 37 had a better survival outcome than BMI less than 28 or 37 or greater; for MELD3, the survival outcome improved with an increasing BMI; for MELD4, the survival outcome was not associated with patient BMI. Conclusions. This study provides evidence that obesity in LT patients is not necessarily associated with higher posttransplantation mortality and highlights the importance of the interaction between BMI and MELD category to determine their survival likelihood.

We report the evolution from ferromagnetic (FM) to antiferromagnetic (AFM) state in CeCu(Ge1−xSnx) investigated by means of magnetic and heat capacity measurements. X-ray diffraction studies for all compositions indicate the ZrBeSi - type hexagonal crystal structure with space group P63/mmc (No. 194). The magnetic susceptibility, χ(T) at high temperature follows the Curie - Weiss relation with an effective magnetic moment close to the value of 2.54 μB expected for free Ce3+ - ion. At low temperatures, χ(T) data indicate AFM transition for alloys in the concentration range 0.7≤x≤1 and FM for x≤0.6. The magnetization, M(μ0H) of samples exhibiting AFM behaviour shows metamagnetic transition at low magnetic fields with some irreversibility in the process of increasing and decreasing magnetic field. In turn, M(μ0H) of samples exhibiting FM behaviour shows saturation in high magnetic fields. Heat capacity, Cp(T) data confirm the AFM and FM transitions observed in magnetic measurements. An additional anomaly below TC and TN is observed in Cp(T)/T, which likely arises from spin reorientation or rearrangement in FM or AFM structure. Below in FM region, Cp(T) can be well described assuming spin-waves excitations with an energy gap ΔC.

Adenylyl cyclase type 5 (AC5), as the principal isoform expressed in striatal medium spiny neurons (MSNs), is essential for the integration of both stimulatory and inhibitory midbrain signals that initiate from dopaminergic G protein-coupled receptor (GPCR) activation. The spatial and temporal control of cAMP signaling is dependent upon the composition of local regulatory protein networks. However, there is little understanding of how adenylyl cyclase protein interaction networks adapt to the multifarious pressures of integrating acute versus chronic and inhibitory vs. stimulatory receptor signaling in striatal MSNs. Here, we presented the development of a novel bimolecular fluorescence complementation (BiFC)-based protein-protein interaction screening methodology to further identify and characterize elements important for homeostatic control of dopamine-modulated AC5 signaling in a neuronal model cell line and striatal MSNs. We identified two novel AC5 modulators: the protein phosphatase 2A (PP2A) catalytic subunit (PPP2CB) and the intracellular trafficking associated protein—NSF (N-ethylmaleimide-sensitive factor) attachment protein alpha (NAPA). The effects of genetic knockdown (KD) of each gene were evaluated in several cellular models, including D1- and D2-dopamine receptor-expressing MSNs from CAMPER mice. The knockdown of PPP2CB was associated with a reduction in acute and sensitized adenylyl cyclase activity, implicating PP2A is an important and persistent regulator of adenylyl cyclase activity. In contrast, the effects of NAPA knockdown were more nuanced and appeared to involve an activity-dependent protein interaction network. Taken together, these data represent a novel screening method and workflow for the identification and validation of adenylyl cyclase protein-protein interaction networks under diverse cAMP signaling paradigms.

Foredunes are important features within coastal landscapes, yet there are relatively few medium to long-term studies on how they evolve and change over time. This study of Australia’s New South Wales (NSW) foredunes has used 70 years of aerial photographs (or photogrammetry) and recent Light Detection and Ranging (LiDAR) datasets to assess multi-decadal fluctuations in foredune morphology. It was shown that over the past 70 years NSW foredunes have exhibited considerable spatial variation, ranging from accretion/aggradation to recession. Those sites that accreted predominantly extended seaward as new incipient dunes, gaining a maximum of 235 m3 m−1 in sand volume over the study period (for the entire dune system). These sites were commonly found in the north of the state, within closed sediment compartments, and with strong onshore (and alongshore) wind climates present (increasing the potential for aeolian sand transport). Stable foredunes were those that remained within +/− 50 m3 m−1 of their initial volume and managed to recover from the various storm impacts over the study period. The majority of these sites were found within the central to southern half of the state, behind embayed beaches, and within leaky sediment compartments, or those that have estuarine sinks. Finally, those foredunes in recession have retreated landwards and/or have reduced in height or width, and lost up to 437 m3 m−1 of sand volume over the study period. There was no clear spatial trend for these sites; however, generally they were found in compartments that had unusual orientations, had disruptions in longshore drift/cross shore sand delivery (i.e., rocky reefs), or were being impacted by humans (i.e., the installation of river training walls, sand bypassing systems, or coastal management programs). This study has shown that NSW foredunes have undergone substantial recent changes and, by understanding their past history, will provide better insight into how they can be managed into the future.

The most widely used ante-mortem diagnostic tests for tuberculosis in cattle are the tuberculin skin test and the interferon-gamma (IFN-γ) release assay, both of which measure cell-mediated immune responses to Mycobacterium bovis infection. However, limitations in the performance of these tests results in a failure to identify all infected animals. In attempting to increase the range of diagnostic tests for tuberculosis, measurement of the cytokine IP-10 in antigen-stimulated blood has previously been shown to improve the detection of M. tuberculosis and M. bovis infection, in humans and African buffaloes (Syncerus caffer), respectively. In the present study, 60 cattle were identified by the single intradermal comparative tuberculin test as tuberculosis reactors (n = 24) or non-reactors (n = 36) and the release of IFN-γ and IP-10 in antigen-stimulated whole blood from these animals was measured using bovine specific ELISAs. There was a strong correlation between IP-10 and IFN-γ production in these samples. Moreover, measurement of the differential release of IP-10 in response to stimulation with M. bovis purified protein derivative (PPD) and M. avium PPD distinguished between reactor and non-reactor cattle with a sensitivity of 100% (95% CI, 86%-100%) and a specificity of 97% (95% CI, 85%-100%). These results suggest that IP-10 might prove valuable as a diagnostic biomarker of M. bovis infection in cattle.

BACKGROUND:New mode-of-action insecticides are sought to provide continued control of pesticide resistant arthropod vectors of neglected tropical diseases (NTDs). We previously identified antagonists of the AaDOP2 D1-like dopamine receptor (DAR) from the yellow fever mosquito, Aedes aegypti, with toxicity to Ae. aegypti larvae as leads for novel insecticides. To extend DAR-based insecticide discovery, we evaluated the molecular and pharmacological characteristics of an orthologous DAR target, CqDOP2, from Culex quinquefasciatus, the vector of lymphatic filariasis and West Nile virus. METHODS/RESULTS:CqDOP2 has 94.7% amino acid identity to AaDOP2 and 28.3% identity to the human D1-like DAR, hD1. CqDOP2 and AaDOP2 exhibited similar pharmacological responses to biogenic amines and DAR antagonists in cell-based assays. The antagonists amitriptyline, amperozide, asenapine, chlorpromazine and doxepin were between 35 to 227-fold more selective at inhibiting the response of CqDOP2 and AaDOP2 in comparison to hD1. Antagonists were toxic to both C. quinquefasciatus and Ae. aegypti larvae, with LC50 values ranging from 41 to 208 μM 72 h post-exposure. Orthologous DOP2 receptors identified from the African malaria mosquito, Anopheles gambiae, the sand fly, Phlebotomus papatasi and the tsetse fly, Glossina morsitans, had high sequence similarity to CqDOP2 and AaDOP2. CONCLUSIONS:DAR antagonists represent a putative new insecticide class with activity against C. quinquefasciatus and Ae. aegypti, the two most important mosquito vectors of NTDs. There has been limited change in the sequence and pharmacological properties of the DOP2 DARs of these species since divergence of the tribes Culicini and Aedini. We identified antagonists selective for mosquito versus human DARs and observed a correlation between DAR pharmacology and the in vivo larval toxicity of antagonists. These data demonstrate that sequence similarity can be predictive of target potential. On this basis, we propose expanded insecticide discovery around orthologous DOP2 targets from additional dipteran vectors.

By adopting an essentially fluid dynamic viewpoint we derive the wave structure equation for stationary, fully nonlinear, electrostatic, ion-cyclotron waves. The existence of two fundamental constants of the motion, namely, conservation of momentum flux parallel to the ambient magnetic field, and energy flux parallel to the direction of wave propagation, enables the wave structure equation to be reduced to a first order differential equation, which has solutions that are physically transparent. The analysis shows that sufficiently oblique waves, propagating at sub-ion acoustic speeds, form soliton pulse-like solutions whose amplitudes are greatest for perpendicular propagation. Waves that propagate supersonically have periodic cnoidal waveforms, which are asymmetric about the compressive and rarefactive phases of the wave. It is also shown that there exist critical driver fields for which the end point of the compressive phase goes sonic (in the wave frame), with the consequence that the wave form develops a cusp. It is possible that this trans-sonic, choked flow feature provides a mechanism for the 'spiky' waveforms observed in auroral electric field measurements.

Summary: Adrenocortical carcinoma (ACC) is a rare malignant tumour arising from the adrenal cortex, with an estimated annual incidence of one to two patients per million. Ectopic ACCs are extremely rare. The majority of ACCs are sporadic; however, ACC has been linked with genetic disease processes, including multiple endocrine neoplasia type-1 (MEN-1). We present the case of a 66-year-old lady referred with newly diagnosed diabetes on a background of primary hyperparathyroidism. Examination revealed Cushingoid features, and hormonal evaluation confirmed ACTH-independent Cushing's syndrome. Morning cortisol after a 1 mg overnight dexamethasone suppression test was 548 nmol/L with an undetectable ACTH <3.0 pg/mL. Dehydroepiandrosterone sulphate was 5.3 μmol/L and androstenedione 3.49 nmol/L, both of which were normal. Testosterone was suppressed at <0.4 nmol/L. Imaging revealed a 6 × 6 × 4.5 cm right-sided presumed adrenal lesion, a pancreatic lesion (2.5 × 1.6 cm), and bilateral pulmonary nodules (0.9 × 0.8 cm, 0.7 × 0.6 cm, 0.3 cm). Right adrenalectomy was performed, and histology was consistent with an extra-adrenal ACC (Weiss score 5/9) within the peri-adrenal adipose tissue. The resected adrenal gland was normal. Lung biopsy confirmed metastatic ACC tissue, and endoscopic ultrasound-guided biopsy of the pancreatic lesion revealed a pancreatic neuroendocrine tumour, which was confirmed biochemically to be an insulinoma. Genetic assessment confirmed MEN-1. This case highlights the importance of screening for MEN-1 in at-risk patients and the need for close clinical follow-up. To our knowledge, this is the first case report of extra-adrenal ACC in MEN-1 syndrome., Learning Points: Adrenal lesions in MEN-1 syndrome have significant malignant potential. Newly diagnosed lesions should be followed closely with short-interval imaging, and a lower threshold for surgical removal is suggested. Primary hyperparathyroidism is often the earliest laboratory or clinical manifestation of MEN-1 syndrome. A detailed medical and family history is vital in order to appropriately identify patients at risk of MEN-1. To our knowledge, this is the first case report of extra-adrenal adrenocortical carcinoma in MEN-1 syndrome.

Dorsal root ganglion (DRG) toxicity has been consistently reported as a potential safety concern after delivery of adeno-associated viruses (AAVs) containing gene-replacement vectors but has yet to be reported for RNAi-based vectors. Here, we report DRG toxicity after AAV intra-CSF delivery of an RNAi expression construct-artificial microRNA targeting superoxide dismutase 1 (SOD1)-in non-human primates (NHPs) and provide evidence that this can be recapitulated within mice. Histopathology evaluation showed that NHPs and mice develop DRG toxicity after AAV delivery, including DRG neuron degeneration and necrosis and nerve-fiber degeneration that were associated with increases in cerebrospinal fluid (CSF) and serum phosphorylated neurofilament heavy chain (pNF-H). RNA-sequencing analysis of DRGs showed that dysregulated pathways were preserved between NHPs and mice, including increases in innate/adaptive immune responses and decreases in mitochondrial- and neuronal-related genes, following AAV treatment. Finally, endogenous miR-21-5p was upregulated in DRGs of AAV-treated NHPs and mice. Increases in miR-21-5p were also identified within the CSF of NHPs, which significantly correlated with pNF-H, implicating miR-21-5p as a potential biomarker of DRG toxicity in conjunction with other molecular analytes. This work highlights the importance of assessing safety concerns related to DRG toxicity when developing RNAi-based AAV vectors for therapeutic purposes., Competing Interests: Declaration of interests M.L.H. is a paid advisor from Charter Preclinical Services. All other authors are or were paid employees at Biogen., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Alport syndrome is a genetically heterogenous disorder resulting from variants in genes coding for alpha-3/4/5 chains of Collagen IV, which results in defective basement membranes in the kidney, cochlea and eye. The syndrome has different inheritance patterns and historically, was thought of as a disease affecting solely males., Case: A 15-year-old female presented with pedal oedema, hypertension and proteinuria. She underwent a kidney biopsy which showed findings in keeping with focal segmental glomerulosclerosis. Her condition was refractory to steroids. Steroid-resistant nephrotic syndrome genetics were sent, revealing a rare pathogenic variant in the COL4A5 gene., Conclusion: Heterozygous females with X-linked Alport syndrome can develop chronic kidney disease and hearing loss. Clinicians should be mindful when reviewing kidney histology to include Alport syndrome as a differential for female patients. COL4A3-5 genes should be included in all steroid-resistant nephrotic syndrome genetic panels., (© 2024. The Author(s).)

Innovative approaches are needed for managing risk and system change in healthcare. This paper presents a case study of a project that took place over two years, taking a systems approach to managing the risk of healthcare acquired infection in an acute hospital setting, supported by an Access Risk Knowledge Platform which brings together Human Factors Ergonomics, Data Science, Data Governance and AI expertise. Evidence for change including meeting notes and use of the platform were studied. The work on the project focused on first systematically building a rich picture of the current situation from a transdisciplinary perspective. This allowed for understanding risk in context and developing a better capability to support enterprise risk management and accountability. From there a linking of operational and risk data took place which led to mapping of the risk pattern in the hospital.

Background: Campylobacter is the most common food-borne pathogen in the European Union. In 2018, the crude incidence rate in Ireland was 63.6 per 100,000 population. Chicken is considered an important source of infection for humans. In 2015, the Campylobacter Stakeholders' Group (CSG) was established to reduce Campylobacter contamination levels in Irish broiler flocks., Aims: This work aimed to describe the Campylobacter monitoring programme that was established by the CSG, to analyse the results of this testing between 2019 and 2022, and to assess progress., Methods and Results: This paper describes the monitoring programme that was established by the CSG, which harmonized Campylobacter enumeration testing across all Irish broiler processors and allowed comparability of results for trend analysis. An analysis of the 2019-2022 data is presented here and compared to previous studies of Campylobacter levels in Irish broilers. An analysis of the 2019-2022 data showed a significant reduction in levels in both caeca and neck skin when the results from 2022 were compared to those from 2019 to 2020. Campylobacter spp. were detected in 37% of caecal samples from first depopulation (pre-thin) broilers and 30% of neck skin samples in 2022, with just 4% of carcases (in neck skin samples) with ≥1000 colony-forming units per gram detected in 2022. Campylobacter levels detected in Irish broilers, in the present monitoring programme were less than those reported in previous studies in both caecal and carcase samples, although not directly comparable for statistical significance because of differences in study methods., Conclusions: The cooperation between stakeholders and regulators of the Irish broiler chicken industry over the past decade has facilitated a coordinated approach to monitoring of Campylobacter levels in broilers, and implementation of control measures. This has enabled a steady reduction in the levels of Campylobacter in Irish chicken., (© 2024 Wiley‐VCH GmbH.)

Background: Compared to other occupational groups, first responders (FR) experience worse mental health outcomes due to duty-related trauma and occupational stressors. Despite their best efforts, they bring this stress home to friends and family. Consequently, FR and their supporters suffer from increased psychosocial difficulties and experience stigma and other barriers to help-seeking. Prior work offers little opportunity for open dialogue and shared understanding of the repercussions of this occupation for all members of the first responder community. In this qualitative study, we aimed to: (i) explore the lived experience of Irish FR and their family members (FM) related to occupational stressors, and (ii) identify opportunities to engage FM with existing organizational supports available for FR., Methods: Using a community based participatory research (CBPR) approach, we conducted six focus groups involving a total of fourteen participants comprising FR, organizational representatives, and FM. All focus groups were audio recorded, transcribed, and analyzed using reflexive thematic analysis., Findings: FR and FM shared their experiences of both joining and learning to live as members of the FR community in Ireland. Through our analysis, we identified a main theme of 'crossing thresholds', characterizing their transformative learning experiences. This learning experience includes recognizing the consequences of this new role for them as individuals and for their relationships. Participants also shared how they have learned to cope with the consequences of their roles and what they need to better support each other., Conclusions: FM are often unheard, hidden members of the first responder community in Ireland, highlighting an unmet need for FR organizations to acknowledge FM role in supporting FR and to provide them with the appropriate training and resources required. Training for new recruits needs to move beyond the tokenistic involvement of FM and encourage knowledge sharing among experienced and novice members. Cultural change is required to support help-seeking among FR and foster a sense of peer support and community among families., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Monoallelic variants in the ALG5 gene encoding asparagine-linked glycosylation protein 5 homolog (ALG5) have been recently shown to disrupt polycystin-1 (PC1) maturation and trafficking via underglycosylation, causing an autosomal dominant polycystic kidney disease-like (ADPKD-like) phenotype and interstitial fibrosis. In this report, we present clinical, genetic, histopathologic, and protein structure and functional correlates of a new ALG5 variant, p.R79W, that we identified in 2 distant genetically related Irish families displaying an atypical late-onset ADPKD phenotype combined with tubulointerstitial damage., Methods: Whole exome and targeted sequencing were used for segregation analysis of available relatives. This was followed by immunohistochemistry examinations of kidney biopsies, and targeted (UMOD, MUC1) and untargeted plasma proteome and N-glycomic studies., Results: We identified a monoallelic ALG5 variant [GRCh37 (NM&#95;013338.5): g.37569565G>A, c.235C>T; p.R79W] that cosegregates in 23 individuals, of whom 18 were clinically affected. We detected abnormal localization of ALG5 in the Golgi apparatus of renal tubular cells in patients' kidney specimens. Further, we detected the pathological accumulation of uromodulin, an N-glycosylated glycosylphosphatidylinositol (GPI)-anchored protein, in the endoplasmic reticulum (ER), but not mucin-1, an O- and N-glycosylated protein. Biochemical investigation revealed decreased plasma and urinary uromodulin levels in clinically affected individuals. Proteomic and glycoproteomic profiling revealed the dysregulation of chronic kidney disease (CKD)-associated proteins., Conclusion: ALG5 dysfunction adversely affects maturation and trafficking of N-glycosylated and GPI anchored protein uromodulin, leading to structural and functional changes in the kidney. Our findings confirm ALG5 as a cause of late-onset ADPKD and provide additional insight into the molecular mechanisms of ADPKD- ALG5 ., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

To gain insight into the accuracy of microbial measurements, it is important to evaluate sources of bias related to sample condition, preservative method and bioinformatic analyses. There is increasing evidence that measurement of the total count and concentration of microbes in the gut, or 'absolute abundance', provides a richer source of information than relative abundance and can correct some conclusions drawn from relative abundance data. However, little is known about how preservative choice can affect these measurements. In this study, we investigated how two common preservatives and short-term storage conditions impact relative and absolute microbial measurements. OMNIgene GUT OMR-200 yields lower metagenomic taxonomic variation between different storage temperatures, whereas Zymo DNA/RNA Shield yields lower metatranscriptomic taxonomic variation. Absolute abundance quantification reveals two different causes of variable Bacteroidetes:Firmicutes ratios across preservatives. Based on these results, we recommend OMNIgene GUT OMR-200 preservative for field studies and Zymo DNA/RNA Shield for metatranscriptomics studies, and we strongly encourage absolute quantification for microbial measurements., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode of transmission. In addition to tools like vaccination and testing, countermeasures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model., Methods: Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to untreated air., Results: Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from the experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a multi-day exposure period during peak viral shedding by hamsters., Conclusions: These findings demonstrate the efficacy of the UV-C light to mitigate against airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool for reducing infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

Purpose of Review: The evaluation of a young athlete with an overuse injury to the knee involves a comprehensive approach. There are a number of elements to consider including assessments of skeletal maturity (biologic maturation), workload (training load + competition load), sport specialization status, and biomechanics. The type of injury and treatment, as well as future prognosis, may be influenced by these and other factors., Recent Findings: Calculating the percentage of predicted adult height (PPAH) is a valuable tool in assessing overuse injury patterns and diagnoses in youth athletes. Modifiable and non-modifiable overuse injury risk factors require monitoring from clinicians as young athletes mature and develop over time. Training and rehabilitation programs should be adapted to account for these. In this manuscript, we seek to introduce a novel, comprehensive approach: S.P.O.R.R.T. (Skeletal Maturity, Prior Injury Risk, One Sport Specialization, Rehabilitation, Return to Play, Training Recommendations) (Fig. 1). Overuse, non-traumatic injuries to the knee in youth athletes will be presented in a case-based and evidence-based model to provide a framework for a comprehensive approach to the assessment and treatment of youth athletes with overuse injuries., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The American Association of Colleges of Nursing (AACN) Core Competencies for Professional Nursing Education (2021) include a Population Health domain. Future nurses well-versed in the social determinants of health are poised to be leaders, creating change to improve the lives of vulnerable populations. The Population Health Project (PHP) is an innovative learning experience, immersing student nurses in authentic interactions that impact the communities they partner with. Baccalaureate nursing students, during their Population Health course, work in groups to produce innovative, community-focused PHPs, successfully incorporating the AACN competencies. Students identify issues impacting the wellbeing of their assigned population; these issues become the focus of their PHP. They engage with community stakeholders, including their patients, policy makers, and community partners to develop evidence-based and sustainable projects. PHPs focus on reducing health disparities and address priorities important to communities, including concepts of diversity, inclusion, and equity. Examples of long-term impacts of PHPs include: legislative change - a new law mandating pharmacies provide prescription labels in a language the patient can understand; innovative policies - initiating efforts to create a hospice for unhoused patients; and new service provision programs - teaming with a fire department to co-develop a home-visiting program to reduce non-emergent 911 calls., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The study of naturally circulating drug metabolites has been a focus of interest, since these metabolites may have different therapeutic and toxicological effects compared to the parent drug. The synthesis of metabolites outside of the human body is vital in order to conduct studies into the pharmacological activities of drugs and bioactive compounds. Current synthesis methods require significant purification and separation efforts or do not provide sufficient quantities for use in pharmacology experiments. Thus, there is a need for simple methods yielding high conversions whilst bypassing the requirement for a separation. Here we have developed and optimised flow chemistry methods in glass microfluidic reactors utilising surface-immobilised enzymes for sulfonation (SULT1a1) and glucuronidation (UGT1a1). Conversion occurs in flow, the precursor and co-factor are pumped through the device, react with the immobilised enzymes and the product is then simply collected at the outlet with no separation from a complex biological matrix required. Conversion only occurred when both the correct co-factor and enzyme were present within the microfluidic system. Yields of 0.97 ± 0.26 μg were obtained from the conversion of resorufin into resorufin sulfate over 2 h with the SULT1a1 enzyme and 0.47 μg of resorufin glucuronide over 4 h for UGT1a1. This was demonstrated to be significantly more than static test tube reactions at 0.22 μg (SULT1a1) and 0.19 μg (UGT1a1) over 4 h. With scaling out and parallelising, useable quantities of hundreds of micrograms for use in pharmacology studies can be synthesised simply., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Strawberry is a high-value commercial crop and a model for the economically important Rosaceae family. Strawberry is vulnerable to attack by many pathogens that can affect different parts of the plant, including the shoot, root, flowers, and berries. To restrict pathogen growth, strawberry produce a repertoire of secondary metabolites that have an important role in defense against diseases. Terpenes, allergen-like pathogenesis-related proteins, and flavonoids are three of the most important metabolites involved in strawberry defense. Genes involved in the biosynthesis of secondary metabolites are induced upon pathogen attack in strawberry, suggesting their transcriptional activation leads to a higher accumulation of the final compounds. The production of secondary metabolites is also influenced by the beneficial microbes associated with the plant and its environmental factors. Given the importance of the secondary metabolite pathways in strawberry defense, we provide a comprehensive overview of their literature and their role in the defense responses of strawberry. We focus on terpenoids, allergens, and flavonoids, and discuss their involvement in the strawberry microbiome in the context of defense responses. We discuss how the biosynthetic genes of these metabolites could be potential targets for gene editing through CRISPR-Cas9 techniques for strawberry crop improvement.

The interface tissue between bone and soft tissues, such as tendon and ligament (TL), is highly prone to injury. Although different biomaterials have been developed for TL regeneration, few address the challenges of the TL-bone interface. Here, we aim to develop novel hybrid nanocomposites based on poly( p -dioxanone) (PDO), poly(lactide- co -caprolactone) (LCL), and hydroxyapatite (HA) nanoparticles suitable for TL-bone interface repair. Nanocomposites, containing 3-10% of both unmodified and chemically modified hydroxyapatite (mHA) with a silane coupling agent. We then explored biocompatibility through in vitro and in vivo studies using a subcutaneous mouse model. Through different characterisation tests, we found that mHA increases tensile properties, creates rougher surfaces, and reduces crystallinity and hydrophilicity. Morphological observations indicate that mHA nanoparticles are attracted by PDO rather than LCL phase, resulting in a higher degradation rate for mHA group. We found that adding the 5% of nanoparticles gives a balance between the properties. In vitro experiments show that osteoblasts' activities are more affected by increasing the nanoparticle content compared with fibroblasts. Animal studies indicate that both HA and mHA nanoparticles (10%) can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. In summary, this work highlights the potential of PDO/LCL/HA nanocomposites as an excellent biomaterial for TL-bone interface tissue engineering applications., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Behzad Shiroud Heidari reports financial support was provided by Western Australia Department of Jobs Tourism Science and Innovation. Barry Doyle reports financial support was provided by Australian Research Council. Minghao Zheng reports financial support was provided by Australian Research Council. Behzad Shiroud Heidari and Barry Doyle have patent #PCT/AU2021/050782 issued to The University of Western Australia., (© 2023 The Authors. Published by Elsevier Ltd.)