Impact of infection preventionists on Centers for Medicare and Medicaid quality measures in Maryland nursing homes.

BackgroundHealth care-associated infections are the leading cause of morbidity and mortality in US nursing homes (NHs). The objective of the research is to assess the impact of Maryland NH infection preventionists (IPs) on NH quality measures.MethodsTwo hundred thirty-four NHs were queried through mailed survey. These survey data were then linked with 2008 quality data from Nursing Home Compare and the On-line Survey Certification of Automated Records.ResultsThree of the 8 quality measures examined-influenza vaccination for both short- and long-stay residents and pressure ulcer prevention in high-risk residents-were significantly associated with the number of IPs. None of the quality measures were shown to be significant with IPs who received specialized training on infection prevention and management compared with those who did not receive specialized training.ConclusionIPs play a critical role in preventing and managing health care-associated infections in nursing homes, especially in the areas of influenza vaccination and pressure ulcer prevention among high-risk nursing home residents. Quality measures that reflect the effects of IP training may not have been elucidated yet. Further research is needed to support the IP role in order for policy to advocate for increased IP funding

Nuclear and Metabolic Quantification for Enhanced Ductal Carcinoma In Situ Risk Stratification

Ductal carcinoma in situ (DCIS) is currently considered an early and localized form of ductal breast cancer stemming from the epithelial ductal cells. These lesions are largely heterogenous, categorized by their morphologies, amount of necrosis, and stromal changes. Even though 10-year mortality rate for DCIS is 1-2.6% while that of early invasive breast cancer is 7-10%. Yet, current recommended treatment for DCIS is breast-conserving surgery and radiation or mastectomy – the same treatment regimen recommended for early invasive breast cancer. This assumes that all DCIS will progress to invasive breast cancer if left untreated. However, mounting evidence indicates that a significant number of DCIS would remain indolence and never progress to invasive cancer. Current risk stratification is based on grade and hormone receptor (estrogen and progesterone) status. While the underlying mechanisms for DCIS to invasive cancer progression are not well understood, an improvement in the quantification of cellular morphology, the extracellular matrix and the metabolism modification of the tumor microenvironment could provide a more accurate and objective prognostication and treatment recommendations. DCIS is currently graded manually by a surgical pathologist using a representative number of areas on the slide. This risks grading bias between different pathologists. By using an automated software to measure quantifiable attributes such as nuclear density, size, and degree of variation of all areas of DCIS on the slide, we can have a more uniform and objective scoring system that would have minimal bias and variation. In addition, we will quantify heterogeneity of collagen arrangement, collagen fiber profile in the stroma as well as the metabolic modifications in the tumor microenvironment of “low risk” vs “high risk” DCIS to determine factors that could provide us with a better prognostication system.https://digitalcommons.unmc.edu/surp2022/1032/thumbnail.jp

Leveraging parasympathetic nervous system activity to study risk for psychopathology: the special case of callous-unemotional traits

Callous-unemotional (CU) traits are implicated in the development of severe and persistent antisocial behavior, and appear to arise from distinct behavioral, temperament, physiological, and neural risk factors to other types of externalizing psychopathology. Although existing etiological models have attempted to characterize specific mechanisms underlying the emergence of CU traits, prior empirical work is plagued by a host of inconsistent results. This inconsistency is particularly apparent in research that has investigated variation in physiological functioning, arousal, and reactivity. In this review, we summarize and evaluate studies that have examined the role of parasympathetic nervous system (PNS) functioning in child psychopathology, including studies of CU traits. We argue that the inclusion of measures of PNS activity can significantly enhance our understanding of the etiology of CU traits, provide clarity to the inconsistent findings of prior studies, and advance mechanistically-targeted interventions and treatments. We conclude the review by providing foundational and testable hypotheses about the role that disrupted PNS functioning could play in multiple pathways to CU traits beginning in infancy and across development.First author draf

Dimensions of Maternal Parenting and Infants’ Autonomic Functioning Interactively Predict Early Internalizing Behavior Problems

Developmental pathways to childhood internalizing behavior problems are complex, with both environmental and child-level factors contributing to their emergence. The authors use data from a prospective longitudinal study (n = 206) to examine the associations between dimensions of caregiving experiences in the first year of life and anxious/depressed and withdrawn behaviors in early childhood. Additionally, the authors examine the extent to which these associations were moderated by infants’ autonomic functioning in the first year of life indexed using measures of respiratory sinus arrhythmia (RSA) and heart period (HP). Findings suggest that higher levels of maternal sensitivity in infancy are associated with fewer anxious/depressed and withdrawn behaviors at age 3 years. Negative intrusiveness was found to be positively associated with children’s anxious/depressed behaviors but not withdrawn behaviors. Further, moderation analyses suggested that the link between negative intrusive parenting during infancy and subsequent anxious/depressed behaviors is exacerbated for infants with average or low baseline HP and that positive engaging parenting during infancy was negatively related to withdrawn behaviors for infants demonstrating average to high levels baseline HP. Interestingly, RSA was not found to moderate the associations between parenting in infancy and later internalizing behavior problems suggesting that, during infancy, overall autonomic functioning may have greater implications for the development of internalizing behaviors than do parasympathetic influences alone. Implications of these findings and future directions for research are discussed

An Ecological Systems Perspective on Individual Differences in Children\u27s Performance on Measures of Executive Function

The predictive validity of performance on cognitive-behavioral measures of executive function (EF) suggests that these measures index children\u27s underlying capacity for self-regulation. In this paper, we apply ecological systems theory to critically evaluate this assertion. We argue that as typically administered, standard measures of EF do not index children\u27s underlying, trait-like capacity for EF, but rather assess their state-like EF performance at a given point in time and in a particular (and often quite peculiar) context. This underscores the importance of disentangling intra-individual (i.e., state-like) and inter-individual (trait-like) differences in performance on these measures and understanding how factors at various levels of organization may contribute to both. To this end, we offer an approach that combines the collection of repeated measures of EF with a multilevel modeling framework, and conclude by discussing the application of this approach to the study of educational interventions designed to foster children\u27s EF

Covalent inhibitors of LgtC: a blueprint for the discovery of non-substrate-like inhibitors for bacterial glycosyltransferases

Non-substrate-like inhibitors of glycosyltransferases are sought after as chemical tools and potential lead compounds for medicinal chemistry, chemical biology and drug discovery. Here, we describe the discovery of a novel small molecular inhibitor chemotype for LgtC, a retaining α-1,4-galactosyltransferase involved in bacterial lipooligosaccharide biosynthesis. The new inhibitors, which are structurally unrelated to both the donor and acceptor of LgtC, have low micromolar inhibitory activity, comparable to the best substrate-based inhibitors. We provide experimental evidence that these inhibitors react covalently with LgtC. Results from detailed enzymological experiments with wild-type and mutant LgtC suggest the non-catalytic active site residue Cys246 as a likely target residue for these inhibitors. Analysis of available sequence and structural data reveals that non-catalytic cysteines are a common motif in the active site of many bacterial glycosyltransferases. Our results can therefore serve as a blueprint for the rational design of non-substrate-like, covalent inhibitors against a broad range of other bacterial glycosyltransferases

Use of Two Self-referral Reminders and a Theory-Based Leaflet to Increase the Uptake of Flexible Sigmoidoscopy in the English Bowel Scope Screening Program: Results From a Randomized Controlled Trial in London

Background We previously initiated a randomized controlled trial to test the effectiveness of two self-referral reminders and a theory-based leaflet (sent 12 and 24 months after the initial invitation) to increase participation within the English Bowel Scope Screening program. Purpose This study reports the results following the second reminder. Methods Men and women included in the initial sample (n = 1,383) were re-assessed for eligibility 24 months after their invitation (12 months after the first reminder) and excluded if they had attended screening, moved away, or died. Eligible adults received the same treatment they were allocated 12 months previous, that is, no reminder (“control”), or a self-referral reminder with either the standard information booklet (“Reminder and Standard Information Booklet”) or theory-based leaflet designed using the Behavior Change Wheel (“Reminder and Theory-Based Leaflet”). The primary outcome was the proportion screened within each group 12 weeks after the second reminder. Results In total, 1,218 (88.1%) individuals were eligible. Additional uptake following the second reminder was 0.4% (2/460), 4.8% (19/399), and 7.9% (29/366) in the control, Reminder and Standard Information Booklet, and Reminder and Theory-Based Leaflet groups, respectively. When combined with the first reminder, the overall uptake for each group was 0.7% (3/461), 14.5% (67/461), and 21.5% (99/461). Overall uptake was significantly higher in the Reminder and Standard Information Booklet and Reminder and Theory-Based Leaflet groups than in the control (odds ratio [OR] = 26.1, 95% confidence interval [CI] = 8.1–84.0, p < .001 and OR = 46.9, 95% CI = 14.7–149.9, p < .001, respectively), and significantly higher in the Reminder and Theory-Based Leaflet group than in the Reminder and Standard Information Booklet group (OR = 1.8, 95% CI = 1.3–2.6, p < .001). Conclusion A second reminder increased uptake among former nonparticipants. The added value of the theory-based leaflet highlights a potential benefit to reviewing the current information booklet. Trials Registry Number ISRCTN44293755

The accuracy and robustness of plasma biomarker models for amyloid PET positivity

Background: Plasma biomarkers for Alzheimer’s disease (AD) have broad potential as screening tools in primary care and disease-modifying trials. Detecting elevated amyloid-β (Aβ) pathology to support trial recruitment or initiating Aβ-targeting treatments would be of critical value. In this study, we aimed to examine the robustness of plasma biomarkers to detect elevated Aβ pathology at different stages of the AD continuum. Beyond determining the best biomarker—or biomarker combination—for detecting this outcome, we also simulated increases in inter-assay coefficient of variability (CV) to account for external factors not considered by intra-assay variability. With this, we aimed to determine whether plasma biomarkers would maintain their accuracy if applied in a setting which anticipates higher variability (i.e., clinical routine). Methods: We included 118 participants (cognitively unimpaired [CU, n = 50], cognitively impaired [CI, n = 68]) from the ADNI study with a full plasma biomarker profile (Aβ42/40, GFAP, p-tau181, NfL) and matched amyloid imaging. Initially, we investigated how simulated CV variations impacted single-biomarker discriminative performance of amyloid status. Then, we evaluated the predictive performance of models containing different biomarker combinations, based both on original and simulated measurements. Plasma Aβ42/40 was represented by both immunoprecipitation mass spectrometry (IP-MS) and single molecule array (Simoa) methods in separate analyses. Model selection was based on a decision tree which incorporated Akaike information criterion value, likelihood ratio tests between the best-fitting models and, finally, and Schwartz’s Bayesian information criterion. Results: Increasing variation greatly impacted the performance of plasma Aβ42/40 in discriminating Aβ status. In contrast, the performance of plasma GFAP and p-tau181 remained stable with variations >20%. When biomarker models were compared, the models “AG” (Aβ42/40 + GFAP; AUC = 86.5), “A” (Aβ42/40; AUC = 82.3), and “AGP” (Aβ42/40 + GFAP + p-tau181; AUC = 93.5) were superior in determining Aβ burden in all participants, within-CU, and within-CI groups, respectively. In the robustness analyses, when repeating model selection based on simulated measurements, models including IP-MS Aβ42/40 were also most often selected. Simoa Aβ42/40 did not contribute to any selected model when used as an immunoanalytical alternative to IP-MS Aβ42/40. Conclusions: Plasma Aβ42/40, as quantified by IP-MS, shows high performance in determining Aβ positivity at all stages of the AD continuum, with GFAP and p-tau181 further contributing at CI stage. However, between-assay variations greatly impacted the performance of Aβ42/40 but not that of GFAP and p-tau181. Therefore, when dealing with between-assay CVs that exceed 5%, plasma GFAP and p-tau181 should be considered for a more robust determination of Aβ burden in CU and CI participants, respectively

Vertical transport and electroluminescence in InAs/GaSb/InAs structures: GaSb thickness and hydrostatic pressure studies

We have measured the current-voltage (I-V) of type II InAs/GaSb/InAs double heterojunctions (DHETs) with 'GaAs like' interface bonding and GaSb thickness between 0-1200 \AA. A negative differential resistance (NDR) is observed for all DHETs with GaSb thickness $>$ 60 \AA below which a dramatic change in the shape of the I-V and a marked hysteresis is observed. The temperature dependence of the I-V is found to be very strong below this critical GaSb thickness. The I-V characteristics of selected DHETs are also presented under hydrostatic pressures up to 11 kbar. Finally, a mid infra-red electroluminescence is observed at 1 bar with a threshold at the NDR valley bias. The band profile calculations presented in the analysis are markedly different to those given in the literature, and arise due to the positive charge that it is argued will build up in the GaSb layer under bias. We conclude that the dominant conduction mechanism in DHETs is most likely to arise out of an inelastic electron-heavy-hole interaction similar to that observed in single heterojunctions (SHETs) with 'GaAs like' interface bonding, and not out of resonant electron-light-hole tunnelling as proposed by Yu et al. A Zener tunnelling mechanism is shown to contribute to the background current beyond NDR.Comment: 8 pages 12 fig

Morpholino-mediated Knockdown of DUX4 Toward Facioscapulohumeral Muscular Dystrophy Therapeutics

Derepression of DUX4 in skeletal muscle has emerged as a likely cause of pathology in facioscapulohumeral muscular dystrophy (FSHD). Here we report on the use of antisense phosphorodiamidate morpholino oligonucleotides to suppress DUX4 expression and function in FSHD myotubes and xenografts. The most effective was phosphorodiamidate morpholino oligonucleotide FM10, which targets the polyadenylation signal of DUX4. FM10 had no significant cell toxicity, and RNA-seq analyses of FSHD and control myotubes revealed that FM10 down-regulated many transcriptional targets of DUX4, without overt off-target effects. Electroporation of FM10 into FSHD patient muscle xenografts in mice also down-regulated DUX4 and DUX4 targets. These findings demonstrate the potential of antisense phosphorodiamidate morpholino oligonucleotides as an FSHD therapeutic option