Search

Increased engagement of nurse practitioners (NPs) has been recommended as a way to address care delivery challenges in settings that struggle to attract physicians, such as primary care and rural areas. Nursing homes also face such physician shortages. We evaluated the role of state scope of practice regulations on NP practice in nursing homes in 2012-2019. Using linear probability models, we estimated the proportion of NP-delivered visits to patients in nursing homes as a function of state scope of practice regulations. Control variables included county demographic, socioeconomic, and health care workforce characteristics; state fixed effects; and year indicators. The proportion of nursing home visits conducted by NPs increased from 24% in 2012 to 42% in 2019. Expanded scope of practice regulation was associated with a greater proportion and total volume of nursing home visits conducted by NPs in counties with at least 1 NP visit. These relationships were concentrated among short-stay patients in urban counties. Removing scope of practice restrictions on NPs may address clinician shortages in nursing homes in urban areas where NPs already practice in nursing homes. However, improving access to advanced clinician care for long-term care residents and for patients in rural locations may require additional interventions and resources.

AbstractRNA-binding proteins (RBPs) are emerging as a novel class of therapeutic targets in cancer, including in leukemia, given their important role in posttranscriptional gene regulation, and have the unexplored potential to be combined with existing therapies. The RBP insulin-like growth factor 2 messenger RNA-binding protein 3 (IGF2BP3) has been found to be a critical regulator of MLL-AF4 leukemogenesis and represents a promising therapeutic target. Here, we study the combined effects of targeting IGF2BP3 and menin-MLL interaction in MLL-AF4-driven leukemia in vitro and in vivo, using genetic inhibition with CRISPR-Cas9-mediated deletion of Igf2bp3 and pharmacologic inhibition of the menin-MLL interaction with multiple commercially available inhibitors. Depletion of Igf2bp3 sensitized MLL-AF4 leukemia to the effects of menin-MLL inhibition on cell growth and leukemic initiating cells in vitro. Mechanistically, we found that both Igf2bp3 depletion and menin-MLL inhibition led to increased differentiation in vitro and in vivo, seen in functional readouts and by gene expression analyses. IGF2BP3 knockdown had a greater effect on increasing survival and attenuating disease than pharmacologic menin-MLL inhibition with small molecule MI-503 alone and showed enhanced antileukemic effects in combination. Our work shows that IGF2BP3 is an oncogenic amplifier of MLL-AF4-mediated leukemogenesis and a potent therapeutic target, providing a paradigm for targeting leukemia at both the transcriptional and posttranscriptional level.

INTRODUCTION: The A/T/N (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimers disease (AD) diagnosis and can encompass additional changes such as inflammation (I). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age. HIGHLIGHTS: Plasma pTau-181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau-181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS-cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithiums possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P

Purpose – The purpose of this qualitative instrumental case study was to determine the perceptions of preservice teachers (PSTs) on the effectiveness of instructional rounds as a clinical experience in promoting awareness of student diversity and supporting the acquisition of professional knowledge (Essential 2). Design/methodology/approach – The instructional rounds were implemented in a junior-level general pedagogy course prior to formal clinical experiences. Professional development school (PDS) personnel supported the course instructors by scheduling the classroom observations, supervising groups of PSTs and debriefing the PSTs after each observation (Essentials 4 and 8). The data were collected through an end-of-course survey of 18 secondary PSTs. Findings – There were several themes that emerged from the analysis of data. First, the study revealed that PSTs credited the variety of campuses visited as supporting their awareness of student diversity and varied instructional strategies. Second, PSTs acknowledged that the instructional rounds supported their connection of theory to practice. Finally, over 70% of the participants noted that they most enjoyed in-person experiences in different classrooms to observe students and teachers in action. Research limitations/implications – The findings for this study were specific to the teacher preparation program (TPP) utilized for the research. Each TPP requires different coursework and clinical experiences; therefore, the inclusion of instructional rounds may not be possible in all programs. Yet, the implementation of the rounds as a PST experience prior to clinical experiences is a strategy to consider to support the preparation of PSTs for their clinical experiences. Originality/value – This study supports the continuation of instructional rounds at the teacher preparation program where the research was conducted. This research also informs other TPPs that strive to provide early clinical experiences that support PSTs’ emerging perceptions of student diversity and applications of instructional knowledge.

OBJECTIVE: Delirium is one of the most frequent syndromes among elderly patients admitted to emergency units and, despite presenting well-established symptoms and signs, there are still diagnostic failures. Thus, the aim of the study was to adapt the Abbreviated Mental Test (AMT) as a screening tool for delirium in elderly adults admitted to an emergency department. METHODS: This cross-sectional study was conducted at the emergency department of a university hospital in Brasília, Brazil between April and June, 2014. We evaluated 90 patients of both sexes, aged 60 years or older. The Confusion Assessment Method (CAM) Instrument was considered the gold standard for diagnosing delirium. The complete translated AMT, administered in four different culturally adapted models, as well as condensed models, were compared to the CAM receiver operating characteristics curve (significance < 0.05; H0: AUC = 0.5). Inter-rater agreement was evaluated with the kappa test, using SPSS version 22.0.0.0. RESULTS: The prevalence of delirium was 25.6%. The best of the four AMT models presented sensitivity and specificity of 78.3% and 85.1%, respectively, with good inter-rater reproducibility (Kappa = 0.793). The best condensed model included four questions, with sensitivity and specificity of 82.6% and 82.1%, respectively, and a kappa of 0.746. CONCLUSIONS: Compared to the gold standard, the adapted AMT (complete or condensed) was adequate as an alternative for quick delirium screening in elderly patients admitted to an emergency department, especially for unaccompanied patients with no prior cognitive deficit.

Abstract We introduce a seismic event detector that applies signal analysis in the time and frequency domains. Signals are searched for with matching coincidences at neighbouring recording stations in space and time. No a priori waveform information is needed for the Adaptive 6-Dimensional Floating-search Multi-station Seismic-event Detector (A6-DFMSD). It combines a short / long time average algorithm (STA/LTA), frequency range selection, energy envelope matching, and backprojection techniques to find a robust detection model. As a challenging test example, the new detector is tuned and applied to a dataset with five months of microearthquake (ML

Abstract Background Most reviews of nutrition-sensitive programs assess the evidence base for nutrition outcomes without considering how programs were delivered. Process evaluations can fill this void by exploring how or why impacts were or were not achieved. This mid-term process evaluation examines a home garden intervention implemented in a large-scale, livelihoods improvement program in Odisha, India. The objectives are to understand whether the intervention was operating as planned (fidelity), investigate potential pathways to achieve greater impact, and provide insights to help design future home garden programs. Methodology Data collection and analysis for this theory-driven process evaluation are based on a program impact pathway that shows the flow of inputs, processes, outputs, outcomes, and impacts. Quantitative and qualitative data from focus group discussions, semi-structured interviews, and a Process Net-Mapping exercise with beneficiaries, frontline workers, and program management staff. Results Despite a mismatch between the design and implementation (low fidelity), the process evaluation identified positive outputs, outcomes, and impacts on home garden production, consumption, income, health and nutritional outcomes, and women’s empowerment. Flexibility led to greater positive outcomes on nutrition, the adoption of sustainable agricultural practices and easy-to-understand nutrition models, and the likelihood of the intervention being sustained after the program ends. Conclusions To help food systems in rural settings reduce food insecurity by utilizing more sustainable agricultural practices, we recommend that home garden interventions include instruction on easy-to-understand nutrition models and on how to make natural fertilizer. Finding local solutions like home gardens to help address critical supply issues and food insecurity is paramount.

Abstract Background The development of drug policies has been a major focus for policy-makers across North America in light of the ongoing public health emergency caused by the overdose crisis. In this context, the current study examined stakeholders’ experiences and perceptions of power and value in a drug policy-making process in a North American city using qualitative, questionnaire, and social network data. Methods We interviewed 18 people who participated in the development of a drug policy proposal between October 2021 and March 2022. They represented different groups and organizations, including government (n = 3), people who use drugs-led advocacy organizations (n = 5), other drug policy advocacy organizations (n = 5), research (n = 3) and police (n = 2). Most of them identified as men (n = 8) and white (n = 16), and their ages ranged between 30 and 80 years old (median = 50). Social network analysis questionnaires and semi-structured qualitative interviews were administered via Zoom. Social network data were analysed using igraph in R, and qualitative data were analysed using thematic analysis. The analyses explored perceptions of value and power within a drug policy-making network. Results The policy-making network showed that connections could be found across participants from different groups, with government officials being the most central. Qualitative data showed that inclusion in the network and centrality did not necessarily translate into feeling powerful or valued. Many participants were dissatisfied with the process despite having structurally advantageous positions or self-reporting moderately high quantitative value scores. Participants who viewed themselves as more valued acknowledged many process shortcomings, but they also saw it as more balanced or fair than those who felt undervalued. Conclusions While participation can make stakeholders and communities feel valued and empowered, our findings highlight that inclusion, position and diversity of connections in a drug policy-making network do not, in and of itself, guarantee these outcomes. Instead, policy-makers must provide transparent terms of reference guidelines and include highly skilled facilitators in policy discussions. This is particularly important in policy processes that involve historical power imbalances in the context of a pressing public health emergency.

Personal laser scanning (PLS) systems are gaining popularity in forest inventory research and practice. They are primarily utilized on circular or compact rectangular sample plots to mitigate potential instrument drift and enhance tree detection rates, and a closed-loop scan path is usually implemented to achieve these objectives, ensuring thorough coverage of the plot. This study introduced a novel approach by applying the distance-sampling framework to PLS data collected during walks along line transects. Modeling the distance-dependent probability of tree detection using PLS coupled with automatic routines for point cloud processing aimed to ascertain the optimal width of line-plots to maximize tree detection rates. The optimized plots exhibited tree detection rates exceeding 99%, which facilitated accurate estimates of tree density, basal area, and growing stock volumes. This proposed method demonstrated considerable potential for data collection while walking along line transects in forests. For instance, the otherwise unproductive working time of field crews moving between systematically arranged sample plots can be utilized for additional data collection without generating additional costs. This innovative approach not only enhances operational efficiency but also establishes a foundation for further advancements to explore PLS applications in forest management practices.

Vitamin D3 transporter (DBP) is a multifunctional protein. Site-specific deglycosylation results in its conversion to group-specific component protein-derived macrophage activating factor (GcMAF), which is capable of activating macrophages. It has been shown that depending on precursor conversion conditions, the resulting GcMAF activates mouse peritoneal macrophages towards synthesis of either pro- (IL-1β, TNF-α—M1 phenotype) or anti-inflammatory (TGF-β, IL-10—M2 phenotype) cytokines. The condition for the transition of the direction of the inflammatory response of macrophages when exposed to GcMAF is the initial glycosylated state of the population of DBP molecules and the associated effective deglycosylation of DBP by β-galactosidase. In vivo experiments with GcMAF exhibiting anti-inflammatory properties on models of induced arthritis in mice and cystitis in rats indicate a significant anti-inflammatory effect of the macrophage activator. The feasibility of unidirectional induction of anti-inflammatory properties of macrophages allows creation of combined therapeutic platforms where M2 macrophages are among the key therapeutic components.

Abstract Neuroligin-2 (Nlgn2) is a key synaptic adhesion protein at virtually all GABAergic synapses, which recruits GABAARs by promoting assembly of the postsynaptic gephyrin scaffold. Intriguingly, loss of Nlgn2 differentially affects subsets of GABAergic synapses, indicating that synapse-specific interactors and redundancies define its function, but the nature of these interactions remain poorly understood. Here we investigated how Nlgn2 function in hippocampal area CA1 is modulated by two proposed interaction partners, MDGA1 and MDGA2. We show that loss of MDGA1 expression, but not heterozygous deletion of MDGA2, ameliorates the abnormal cytosolic gephyrin aggregation, the reduction in inhibitory synaptic transmission and the exacerbated anxiety-related behaviour characterizing Nlgn2 knockout (KO) mice. Additionally, combined Nlgn2 and MDGA1 deletion causes an exacerbated layer-specific loss of gephyrin puncta. Given that both Nlgn2 and the MDGA1 have been correlated with many psychiatric disorders, our data support the notion that cytosolic gephyrin aggregation may represent an interesting target for novel therapeutic strategies.

Abstract Background The market for beverages is highly changing within the last years. Increasing consumer awareness towards healthier drinks led to the revival of traditional and the creation of innovative beverages. Various protein-rich legumes were used for milk analogues, which might be also valuable raw materials for refreshing, protein-rich beverages. However, no such applications have been marketed so far, which might be due to unpleasant organoleptic impressions like the legume-typical “beany” aroma. Lactic acid fermentation has already been proven to be a remedy to overcome this hindrance in consumer acceptance. Results In this study, a statistically based approach was used to elucidate the impact of the fermentation parameters temperature, inoculum cell concentration, and methionine addition on the fermentation of lupine- and faba bean-based substrates. A total of 39 models were found and verified. The majority of these models indicate a strong impact of the temperature on the reduction of aldehydes connected to the “beany” impression (e.g., hexanal) and on the production of pleasantly perceived aroma compounds (e.g., β-damascenone). Positively, the addition of methionine had only minor impacts on the negatively associated sulfuric compounds methional, dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide. Moreover, in further fermentations, the time was added as an additional parameter. It was shown that the strains grew well, strongly acidified the both substrates (pH ≤ 4.0) within 6.5 h, and reached cell counts of > 9 log10 CFU/mL after 24 h. Notably, most of the aldehydes (like hexanal) were reduced within the first 6–7 h, whereas pleasant compounds like β-damascenone reached high concentrations especially in the later fermentation (approx. 24–48 h). Conclusions Out of the fermentation parameters temperature, inoculum cell concentration, and methionine addition, the temperature had the highest influence on the observed aroma and taste active compounds. As the addition of methionine to compensate for the legume-typical deficit did not lead to an adverse effect, fortifying legume-based substrates with methionine should be considered to improve the bioavailability of the legume protein. Aldehydes, which are associated with the “beany” aroma impression, can be removed efficiently in fermentation. However, terminating the process prematurely would lead to an incomplete production of pleasant aroma compounds.

Abstract Background The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers. The collection of neuroimaging data in a longitudinal, multicenter study requires the implementation of a comprehensive quality assurance (QA) protocol. Here, we outline this protocol and illustrate its application within the BipoLife consortium. Methods The QA protocol consisted of (1) a training of participating research staff, (2) regular phantom measurements to evaluate the MR scanner performance and its temporal stability across the course of the study, and (3) the assessment of the quality of human MRI data by evaluating a variety of image metrics (e.g., signal-to-noise ratio, ghosting level). In this article, we will provide an overview on these QA procedures and show exemplarily the influence of its application on the results of standard neuroimaging analysis pipelines. Discussion The QA protocol helped to characterize the various MR scanners, to record their performance over the course of the study and to detect possible malfunctions at an early stage. It also assessed the quality of the human MRI data systematically to characterize its influence on various analyses. Furthermore, by setting up and publishing this protocol, we define standards that must be considered when analyzing data from the BipoLife consortium. It further promotes a systematic evaluation of data quality and a definition of subject inclusion criteria. In the long term, it will help to increase the chance of achieving clinically relevant results.

Abstract Entangled photon-pair sources are at the core of quantum applications like quantum key distribution, sensing, and imaging. Operation in space-limited and adverse environments such as in satellite-based and mobile communication requires robust entanglement sources with minimal size and weight requirements. Here, we meet this challenge by realizing a cubic micrometer scale entangled photon-pair source in a 3R-stacked transition metal dichalcogenide crystal. Its crystal symmetry enables the generation of polarization-entangled Bell states without additional components and provides tunability by simple control of the pump polarization. Remarkably, generation rate and state tuning are decoupled, leading to equal generation efficiency and no loss of entanglement. Combining transition metal dichalcogenides with monolithic cavities and integrated photonic circuitry or using quasi-phasematching opens the gate towards ultrasmall and scalable quantum devices.

We examine how the racial wealth gap interacts with financial aid in American higher education to generate a disparate impact on college access and outcomes. Retirement savings and home equity are excluded from the formula used to estimate the amount a family can afford to pay. All else equal, omitting those assets mechanically increases the financial aid available to families that hold them. White families are more likely to own those assets and in larger amounts. We document this issue and explore its relationship with observed differences in college attendance, types of institutions attended, degrees attained, and education debt using data from the Survey of Consumer Finances (SCF), the National Postsecondary Student Aid Study (NPSAS), and the Panel Study of Income Dynamics (PSID). We show that this treatment of assets provides an implicit subsidy worth thousands of dollars annually to students from families with above-median incomes. White students receive larger subsidies relative to Black students and Hispanic students with similar family incomes, and this gap in subsidies is associated with disadvantages in educational advancement and student loan levels. It may explain 10 percent to 15 percent of white students' advantage in these outcomes relative to Black students and Hispanic students.