We examine the least squares approximation C to a symmetric matrix B, when all diagonal elements get weight w relative to all nondiagonal elements. WhenB has positivity p and C is constrained to be positive semi-definite, our main result states that, when w ≥1/2, then the rank of C is never greater than p, and when w ≤1/2 then the rank of C is at least p. For the problem of approximating a given n × n matrix with a zero diagonal by a squared-distance matrix, it is shown that the sstress criterion leads to a similar weighted least squares solution with w =(n+2)/4; the main result remains true. Other related problems and algorithmic consequences are briefly discussed.

The escalating threat of antimicrobial resistance (AMR) necessitates impactful, reproducible, and scalable antimicrobial stewardship strategies. This review addresses the critical need to enhance the quality of antimicrobial stewardship intervention research. We propose five considerations for authors planning and evaluating antimicrobial stewardship initiatives. Antimicrobial stewards should consider the following mnemonic ABCDE: (A) plan Ahead using implementation science; (B) Be clear and thoroughly describe the intervention by using the TidIER checklist; (C) Use a Checklist to comprehensively report study components; (D) Select a study Design carefully; and (E) Assess Effectiveness and implementation by selecting meaningful outcomes. Incorporating these recommendations will help strengthen the evidence base of antimicrobial stewardship literature and support optimal implementation of strategies to mitigate AMR.

A new nematode genus and species, Paraspiralatus sakeri , is described from the stomach of a wild-caught, female saker falcon in Saudi Arabia. This spirurid differs from the nearest genus and species Spiralatus baeri Chabaud, Brygoo & Durette, 1963 in the shape of the pseudolabia, shape of the buccal capsule and absence of a large cephalic vesicle. In addition, third stage spirurid larvae were recovered for the first time from subcutaneous tissues of two houbara bustards. These had died in the Rahim Yar Khan Rehabilitation Center (Houbara Foundation International, Lahore, Pakistan) in Pakistan and were examined at the National Avian Research Center in the United Arab Emirates. The morphology of the larvae and host pathology are described. Comparative studies with the adult spirurids from the saker falcon showed each to have similar cephalic and pharyngeal morphological features to the adults described indicating they are probably the same species. Spirurid nematodes of the suborder Spirurina normally have an arthropod intermediate host. In view of the host, the site from which the larvae were recovered and the fact that this is a rare occurrence, the houbara bustard is considered to be a paratenic host.

OBJECTIVES/GOALS: Communities of color often report that their concerns are ignored and desire a means to facilitate effective community-academic engagement, especially during a crisis. The objective is to share lessons learned and challenges faced in the development of an online portal designed to meet this need. METHODS/STUDY POPULATION: The Michigan Institute for Clinical & Health Research (MICHR) worked with community and academics to develop an online tool, the Michigan Research Engaging the Academy and Community in Health (M-REACH) platform. The community-engaged research (CEnR) project involved conducting qualitative interviews exploring connectivity to community and academic organizations and pilot testing of the novel platform. Following development, efforts were made to implement the statewide use of M-REACH. We will report on the challenges encountered and lessons learned from development and optimization of the platform. RESULTS/ANTICIPATED RESULTS: Authors will review the timeline of the launch of M-REACH. Steps to promote engagement of the locally developed platform to statewide utilization will be shared. Challenges encountered with scaling, matching the needs of differing communities both rural and urban, and navigating connections between remote geographies will be presented. Lessons learned and potential solutions will be discussed. DISCUSSION/SIGNIFICANCE: M-REACH can connect partners by increasing understanding of the CEnR process, enhancing alignment, and building a foundation for well-functioning research partnerships. Further work is required to address the challenges encountered in development and implementation.

OBJECTIVES/GOALS: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by dysregulated collagen accumulation in the lung parenchyma. Our goal is to investigate the role of O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in pulmonary fibrosis to ultimately discover novel therapies for fibrosis resolution. METHODS/STUDY POPULATION: Lung tissue from IPF and non-IPF donors was subjected to immunohistochemistry (IHC) to assess O-GlcNAc levels. Primary human lung fibroblasts were treated with OGT or O-GlcNAcase (OGA) inhibitors followed by transforming growth factor-beta 1 (TGF-β1) stimulation to assess O-GlcNAc regulation of fibroblast-to-myofibroblast transition (FMT) markers [alpha smooth muscle actin (α-SMA) and type 1 and type 3 collagen (COL1α1, COL3α1)] In Drosophila melanogaster, OGT knockdown (KD)/overexpression (OE) was conditionally induced to assess pericardin, a type IV collagen-like protein, regulation by immunofluorescence. Lastly, a mouse model of bleomycin-induced pulmonary fibrosis was examined following OGT KD and assessed for fibrosis resolution via histology, hydroxyproline assay, and western blotting. RESULTS/ANTICIPATED RESULTS: O-GlcNAc staining was increased in IPF lung tissue compared to non-IPF control lungs. In primary human lung fibroblasts, TGF-α1 administration resulted in increased FMT markers (α-SMA, COL1α1, and COL3α1), which were reduced or increased by OGT or OGA inhibition, respectively. Genetic manipulation in the Drosophila models showed decreased pericardin expression with OGT KD compared to the wild-type, whereas OGT OE increased pericardin compared to control. Additionally, OGT KD in bleomycin treated aged mice resulted in reduced collagen levels at the transcript and protein level and concurrent fibrosis resolution as assessed by Masson’s trichrome staining and total hydroxyproline analysis. Collectively, showing OGT/O-GlcNAc regulating collagen in fibrosis resolution. DISCUSSION/SIGNIFICANCE: These data suggest that the OGT/O-GlcNAc axis regulates collagen deposition in pulmonary fibrosis, and we show that O-GlcNAc is implicated in the pathogenesis of IPF. We identified OGT as a therapeutic target to overcome current drug limitations, opening new horizons for biomedical treatment.

The crystal structure of a magnesian cronstedtite-2H2 from Pribram, Czechoslovakia, was refined in space group C1 to a residual of 5.4% with 1832 independent reflections. Tetrahedral ordering between Fe3+ and Si is judged to be complete on the basis of electron density maps, the first confirmation of such ordering in a layer silicate. Octahedral cations are disordered on the M sites. Mean T-O bond lengths do not confirm the tetrahedral ordering, perhaps due to tetrahedral distortion in order to relieve the extreme corrugation of the sheet that would arise from ordering of such different size cations.

In the initial stages of refinement the structure of the crystal under study could not be described adequately on the basis of a single 2H2 polytype. The structure contains two kinds of 2H2 domains that appear shifted by b/3 relative to one another due to a mistake in the interlayer stacking sequence. This mistake of zero shift (the normal 2H2 polytype consists of alternating —b/3 and +b/3 shifts) affects only the tetrahedral sheets. It creates adjacent enantiomorphic domains of 2H2 packets such that domains with small Si tetrahedra sit above larger Fe3+-rich tetrahedra and vice versa. This mechanism to relieve strain may indeed be the cause of the stacking mistakes. A third kind of domain contains regions in which the sense of tetrahedral rotation is reversed, giving rise to split basal oxygens on electron density maps. This multiple domain model best explains extra atomic positions observed on Fourier maps, lack of streaking of k ≠ 3n reflections, and possible nonintegral “satellitic” reflections observed on Weissenberg films.

The California Department of Public Health (CDPH) reviewed 109 cases of healthcare personnel (HCP) with laboratory-confirmed mpox to understand transmission risk in healthcare settings. Overall, 90% of HCP with mpox had nonoccupational exposure risk factors. One occupationally acquired case was associated with sharps injury while unroofing a patient’s lesion for diagnostic testing.

As a result of an ameliorative shift-to-opposite, the polysemous adjective wicked is an auto-antonym, having two senses opposite in meaning, that is, ‘evil’ and ‘good’. We discuss two studies which explore the social life of this word, with the first focusing on its production and the second on its perception. In the first study, conducted in Cornwall, United Kingdom, we find that young men are most advanced in the use of wicked ‘good’ while young women appear not to contribute to the incrementation, that is, the advancement, of this change. In the second study, conducted online across England, we find wicked ‘good’, relative to its synonym good, to be perceived as less young and to be evaluated positively across disparate characteristics relating to status and solidarity, particularly by older men. We find wicked ‘evil’, in contrast to its synonym evil, to be evaluated higher in status-type characteristics. This newly uncovered indexical field of wicked presents a possible explanation for the observed changes in production, contributing to ongoing questions about the role of social meaning in driving the incrementation of change. More generally, this article adds to the growing yet limited literature which explores semantic variation through the lens of variationist sociolinguistics.

Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel–Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.

The wall dependence of length scales used to describe large- and small-scale structures of turbulence is examined using highly resolved experiments in zero-pressure-gradient turbulent boundary layers and pipe flows spanning the range $2000< Re_\tau <37\ 700$. Of particular interest is the influence of external intermittency on the scaling of these length scales. It is found that when suitable scaling parameters are selected and external intermittency is accounted for, the dissipative motions follow inner scaling even into the outer-scaled regions of the flow, and that certain large-scale descriptions follow outer scaling even in the inner-scaled regions of the flow. The wall dependence is the same for both internal pipe and external boundary layer flows, and the different length scales can be related to recognizable features in the longitudinal wavenumber spectrum.