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Alternative poverty measures have been proposed in response to the emerging insufficiencies of the National School Lunch Program (NSLP) eligibility data. The analysis presented here involves seven poverty measures. Using outcome measures as a yardstick, we can assess how poverty measures explain these outcomes and note variations between geographical locales (assessing predictive validity). An analysis of 2019 data from Montana revealed that no poverty measure emerges as consistently meeting or exceeding the results found with the NSLP on the state level. Results are mixed based on locale (size) and distance from an urban centre, and within school communities.

Early warning systems (EWS) using analytical tools that have been trained against prior years' data, can reliably predict dropout risk in individual students so that educators may intervene early to help avert this from happening. Risk profiles for dropouts aren't always useful since students often do not conform to the profiles. Researchers with the Montana Office of Public Instruction developed objective, evidence-based indicators that respond to student context. These indicators show when a student may be at risk and provide signs of when to intervene.

Neuropilin-1 acts as a coreceptor with vascular endothelial growth factor receptors to facilitate binding of its ligand, vascular endothelial growth factor. Neuropilin-1 also binds to heparan sulfate, but the functional significance of this interaction has not been established. A combinatorial library screening using heparin oligosaccharides followed by molecular dynamics simulations of a heparin tetradecasaccharide suggested a highly conserved binding site composed of amino acid residues extending across the b1 and b2 domains of murine neuropilin-1. Mutagenesis studies established the importance of arginine513 and lysine514 for binding of heparin to a recombinant form of Nrp1 composed of the a1, a2, b1, and b2 domains. Recombinant Nrp1 protein bearing R513A,K514A mutations showed a significant loss of heparin-binding, heparin-induced dimerization, and heparin-dependent thermal stabilization. Isothermal calorimetry experiments suggested a 1:2 complex of heparin tetradecasaccharide:Nrp1. To study the impact of altered heparin binding in vivo, a mutant allele of Nrp1 bearing the R513A,K514A mutations was created in mice (Nrp1D) and crossbred to Nrp1+/- mice to examine the impact of altered heparan sulfate binding. Analysis of tumor formation showed variable effects on tumor growth in Nrp1D/D mice, resulting in a frank reduction in tumor growth in Nrp1D/- mice. Expression of mutant Nrp1D protein was normal in tissues, suggesting that the reduction in tumor growth was due to the altered binding of heparin/heparan sulfate to neuropilin-1. These findings suggest that the interaction of neuropilin-1 with heparan sulfate modulates its stability and its role in tumor formation and growth.

The draft dodgers and other political émigrés always seemed American to me in their very rejection of American life and attitudes. They, after all, knew what they were repudiating far better than the people among whom they made a new life. Even if they learned to speak with a Canadian accent, their own preoccupation with the nation they had left was quite different from that of Canadian friends ..., W HEN support for the Vietnam War was collapsing among young Americans in the late 1960s, and thousands of draft-age men were seeking refuge north of the border, a satirical [...]

A novel approach for determining triaxial residual stress states by coupling energy dispersive X-ray diffraction and contour method measurements is provided and validated in a Ti‐5Al‐5V‐5Mo‐3Cr additive manufactured (AM) bridge sample. Synchrotron X-ray diffraction (SXRD) can provide relatively fine spatial resolution (on the order of 10–100 µm) for mapping 3D elastic strain fields within a sample. However, for samples with dimensions larger than one or two centimeters the path length can get prohibitive as both constant wavelength and energy dispersive SXRD are based upon transmission measurements. As an example, for a plate-like sample geometry where the thickness is limited (less than a centimeter) it is trivial to measure the longitudinal and height direction elastic strain components with excellent in-plane spatial resolution (∼100 µm) and a somewhat lower through-thickness resolution (10–15 times larger) but obtaining the through thickness component is often not possible as the beam path must be parallel to one of the large dimensions of the plate. While small samples of low Z-number alloys (e.g., Ti or Al) allow determination of the three elastic strain components, this is often not the case for higher Z alloys (e.g., Fe or Ni) or large samples where some strain components can be indeterminable. To overcome these limitations, this work applies a combination of synchrotron X-ray diffraction and the contour method (a mechanical relaxation technique), to determine the triaxial stress state. This novel combination is demonstrated and validated in a relatively small additive manufactured sample where all three orthogonal strain components are accessible via X-ray diffraction for stress determination. The paper also explores methods for determining the strain-free lattice parameter, typically obtained from a small stress-free reference sample. This work shows that a small size AM sample is not stress free, producing unreliable magnitudes of strain and stress. Instead, a strain-free lattice parameter is determined using residual stress equilibrium conditions, which gives consistent strain and stress trends for both X-ray diffraction (alone) and the new diffraction-contour coupling technique. This demonstrates that the coupling technique can be confidently applied to samples to determine stress when path length (size or Z-number) prohibit determination of three orthogonal strain components via diffraction.

Abstract Fungal infections pose a great threat to public health and there are only four main types of antifungal drugs, which are often limited with toxicity, drug-drug interactions and antibiotic resistance. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. Here we report the discovery of alligamycin A (1) as an antifungal compound from the rapamycin-producer Streptomyces iranensis through genome-mining, genetics and natural product chemistry approaches. Alligamycin A harbors a unique chemical scaffold with 13 chiral centers, featuring a β-lactone moiety, a [6,6]-spiroketal ring, and an unreported 7-oxo-octylmalonyl-CoA extender unit incorporated by a potential crotonyl-CoA carboxylase/reductase. It is biosynthesized by a type I polyketide synthase which is confirmed through CRISPR-based gene editing. Alligamycin A displayed potent antifungal effects against numerous clinically relevant filamentous fungi, including resistant Aspergillus and Talaromyces species. β-Lactone ring is essential for the antifungal activity since alligamycin B (2) with disruption in the ring abolished the antifungal effect. Proteomics analysis revealed alligamycin A potentially disrupts the integrity of fungal cell walls and induces the expression of stress-response proteins in Aspergillus niger. Discovery of the potent antifungal candidate alligamycin A expands the limited antifungal chemical space.

Abstract Background Assertive Community Treatment (ACT) teams have become a part of mental health services for people with severe mental illness in many high-income countries. Studies in several countries have investigated the outcomes of ACT, and knowledge is also needed about outcomes of ACT teams in Norway. Our aims were to study clinical outcomes of ACT, how the outcomes were associated with characteristics of patients and treatment, and whether they differed across ACT teams. Methods Our explorative, prospective, pre–post multicenter study involved 142 patients who received ACT for two years from the first 12 ACT teams established in urban and rural areas of Norway. There was no control group. The primary outcome was change in clinician-rated psychiatric symptoms. Secondary outcomes were clinician-rated change in functioning and engagement and change in community tenure compared with 2 years prior to ACT. We measured fidelity to the ACT model using the Tool for Measurement of Assertive Community Treatment. We performed linear mixed-effects modeling to analyze outcomes and their associations with characteristics of patients and treatment. Results After two years, psychiatric symptoms were significantly reduced with a small effect size. Negative symptoms, anxiety and depression, and agitation and mania had significant reductions, while positive symptoms had nonsignificant changes. Functioning, engagement, and community tenure all significantly increased with small effect sizes. Age, difficulty to engage, problematic use of alcohol, frequent previous use of inpatient services, total number of sessions, and team’s fidelity to the ACT model were associated with different groups of symptoms. Less improvement in functioning was associated with team fidelity and number of sessions. Change in engagement was not associated with any predictors. Increased community tenure was greater for younger patients and patients who were on community treatment orders at treatment start. Conclusions ACT for two years led to significant positive outcomes with small effect sizes for psychiatric symptoms, functioning, engagement, and community tenure. The outcomes were associated with some potential predictors, and some team-level variance emerged. Positive significant outcomes after two years indicate that larger improvements may be achieved from longer-term treatments by ACT teams.

Abstract Microbiome-directed dietary interventions such as microbiota-directed fibers (MDFs) have a proven track record in eliciting responses in beneficial gut microbes and are increasingly being promoted as an effective strategy to improve animal production systems. Here we used initial metataxonomic data on fish gut microbiomes as well as a wealth of a priori mammalian microbiome knowledge on α-mannooligosaccharides (MOS) and β-mannan-derived MDFs to study effects of such feed supplements in Atlantic salmon (Salmo salar) and their impact on its gut microbiome composition and functionalities. Our multi-omic analysis revealed that the investigated MDFs (two α-mannans and an acetylated β-galactoglucomannan), at a dose of 0.2% in the diet, had negligible effects on both host gene expression, and gut microbiome structure and function under the studied conditions. While a subsequent trial using a higher (4%) dietary inclusion of β-mannan significantly shifted the gut microbiome composition, there were still no biologically relevant effects on salmon metabolism and physiology. Only a single Burkholderia-Caballeronia-Paraburkholderia (BCP) population demonstrated consistent and significant abundance shifts across both feeding trials, although with no evidence of β-mannan utilization capabilities or changes in gene transcripts for producing metabolites beneficial to the host. In light of these findings, we revisited our omics data to predict and outline previously unreported and potentially beneficial endogenous lactic acid bacteria that should be targeted with future, conceivably more suitable, MDF strategies for salmon.

Abstract In this work, we investigated the effects of alloying elements on plastic deformation and microstructure evolution in polycrystalline copper (Cu) and Cu alloyed with 1 wt. $$\%$$ % lead (Cu-1 $$\%$$ % Pb). These materials were selected due to the size mismatch between Cu and Pb, with the latter forming precipitates at grain boundaries. Multi-modal characterization techniques, including neutron diffraction, electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM), along with finite element simulations were employed to study the deformation behavior across multiple length scales. While both Cu and Cu-1 $$\%$$ % Pb exhibited similar macroscale response and final deformation textures, both dislocation line profile analysis and TEM revealed increased dislocation density in deformed Cu-1 $$\%$$ % Pb specimens. The presence of lead precipitates also significantly affected local plastic deformation during compression, with their influence diminishing with increasing strain. These results demonstrate the complex relationships between alloying elements, plastic deformation, microstructural evolution, and material behavior under load. The insights gained from this multi-scale and multi-technique approach contribute to the fundamental understanding of microstructural evolution in immiscible alloys and are valuable for tailoring the properties of structural materials for specific engineering applications.

Abstract Background Participation in society and the ability to perform various activities are crucial aspects of everyday functioning. The intertwined relationship between functioning, disability, and health is emphasized in the “International Classification of Functioning, Disability and Health (ICF)” framework. In recent decades, mental health care units have increasingly focused on this aspect. The Practical and Social Functioning scale (PSF) was developed and validated in Norwegian as an easy-to-administer instrument to assess practical and social functioning among patients with serious mental illness in different clinical settings. Methods The PSF was developed and revised using data from different Norwegian studies. Data from a total of 562 patients with serious mental illness in different clinical settings were included. The validation process included the evaluation of items into categories by 25 professionals. Development and revision took place in three different stages, and factor analyses were conducted. The quality of the PSF was assessed according to the COSMIN standards for systematic reviews on patient-reported outcome measures. Results The final version of the PSF comprises seven subscales, each consisting of four items, resulting in a total of 28 items. These subscales, along with their corresponding items, are loaded onto two factors representing the main dimensions of functioning: activity and participation. Content validity comprises three domains: relevance, comprehensiveness, and comprehensibility. Relevance and comprehensibility were found to be adequate, whereas comprehensiveness was doubtful. Structural validity was adequate, internal consistency was very good, and construct validity was adequate compared to the Global Assessment of Functioning scale. Responsiveness was found to be doubtful in our study with data from an 18-month observation period. Nearly 60% of the items showed a ceiling effect. No items showed a floor effect. Conclusion The development and validation of the Norwegian version of the PSF resulted in an instrument consisting of seven subscales and a total of 28 items. The items and subscales assess functioning related to two key factors according to the ICF framework: activity and participation. Our results show that the PSF is an easy-to-administer instrument that may be particularly sensitive for detecting variation among persons with severely impaired functioning. Trial registration The study Implementation of Guidelines for the Treatment of Psychoses was registered retrospectively on 31 August 2017 at ClinicalTrials.gov (NCT03271242).

Abstract Background Inadequate medication knowledge may contribute to inappropriate medication use and treatment harms. We aimed to map and synthesise the existing evidence on patients’ knowledge of the indications for their medications. Method We searched MEDLINE, Embase, CINAHL, PsychInfo and the Cochrane Library for studies that assessed patients’ knowledge of the indications for their medications from inception to June 16, 2022. A pair of reviewers independently screened and extracted data on study characteristics, aims, and methods used to assess and report patients’ knowledge of the indications for their medications. Results We included 99 studies conducted in 33 countries, published between 1979 and 2021, with 42,377 participants in total (median 126 participants [Interquartile range: 63–338]). Studies were observational (n = 77), experimental (n = 18), or qualitative interviews (n = 4). The exact question used to assess knowledge of the indications was reported in 27 studies and was phrased in 25 different ways. Knowledge of the indications was reported as a proportion of either 1) all participants (n = 65) or 2) the total number of medications used by all patients (n = 13). Sixteen studies used both reporting methods, while five only reported a proportion without specifying the denominator. Fourteen studies in various populations reported the number of participants with correct knowledge of all their medications, ranging from 19% (long-term psychiatric in-patients) to 87% (general practice patients). Conclusion We did not identify any established scientific standard for assessing patients’ knowledge of the indications for their medications. The wide range of study methodologies and reporting styles observed call for a methodological consensus in this research field. Estimates of correct knowledge varied widely between studies, but whether this was due to differences in study populations or study methodology could not be determined. Furthermore, we did not identify any study investigating whether participants’ knowledge of the indications for their medications was associated with the quality, e.g. appropriateness, of their treatment.

Abstract Diseases caused by S. pneumoniae are the leading cause of child mortality. As antibiotic resistance of S. pneumoniae is rising, vaccination remains the most recommended solution. However, the existing pneumococcal polysaccharides vaccine (Pneumovax® 23) proved only to induce T-independent immunity, and strict cold chain dependence of the protein conjugate vaccine impedes its promotion in developing countries, where infections are most problematic. Affordable and efficient vaccines against pneumococcus are therefore in high demand. Here, we present an intranasal vaccine Lipo+CPS12F&αGC, containing the capsular polysaccharides of S. pneumoniae 12F and the iNKT agonist α-galactosylceramide in cationic liposomes. In BALB/cJRj mice, the vaccine effectively activates iNKT cells and promotes B cells maturation, stimulates affinity-matured IgA and IgG production in both the respiratory tract and systemic blood, and displays sufficient protection both in vivo and in vitro. The designed vaccine is a promising, cost-effective solution against pneumococcus, which can be expanded to cover more serotypes and pathogens.

Abstract Background and objective To diagnose tuberculosis infection (TBI), whole blood is incubated with M.tuberculosis (Mtb)-specific peptides and the release of interferon-γ (IFN-γ) is measured in IFN-γ-release assays (IGRAs). Hyperglycaemia and fluctuations in blood glucose may modulate IFN-γ-release. Here, we investigated if glucose intake affects IFN-γ-release or IGRA results in IGRAs taken during an oral glucose tolerance test (OGTT). Methods Persons with TB disease (TB) or TBI underwent a standard 75-g OGTT at the start and end of treatment for TB or TBI. Blood for the IGRA QuantiFERON-TB Gold Plus (QFT) containing Mtb-specific tubes (TB1 and TB2), a non-specific mitogen tube (MIT) and an empty control tube (NIL) was drawn at sample-timepoints -15 (baseline), 60, 90, 120 and 240 min during the OGTT. Blood glucose was measured in parallel at all timepoints. IFN-γ-release (after subtraction of NIL) at each timepoint was compared with baseline using linear-mixed-model analysis. Results Twenty-four OGTTs from 14 participants were included in the final analysis. Compared to baseline, IFN-γ-release was increased at sample-timepoint 240 min for TB1; geometric mean (95% confidence interval) 3.0 (1.5–6.2) vs 2.5 (1.4–4.4) IU/mL (p = 0.047), and MIT; 182.6 (103.3–322.9) vs 146.0 (84.0–254.1) IU/mL (p = 0.002). Plasma glucose levels were not associated with IFN-γ-release and the QFT test results were unaffected by the OGTT. Conclusion Ingestion of glucose after a 10-h fast was associated with increased IFN-γ-release after 240 min in the MIT tube. However, there was no association between plasma glucose levels at the QFT sampling timepoint and IFN-γ-release. Furthermore, the QFT test results were not affected by glucose intake. The overall effect of an OGTT and prevailing plasma glucose levels on IFN-γ-release in IGRAs seem limited. Trial registration Trial registration ID: NCT04830462 ( https://clinicaltrials.gov/study/NCT04830462 ). Registration date: 05-Apr-2021.