Predominantly multiple focal non-cystic renal lesions: an imaging approach.

Multiple non-cystic renal lesions are occasionally discovered during imaging for various reasons and poses a diagnostic challenge to the practicing radiologist. These lesions may appear as a primary or dominant imaging finding or may be an additional abnormality in the setting of multiorgan involvement. Awareness of the imaging appearance of the various entities presenting as renal lesions integrated with associated extrarenal imaging findings along with clinical information is crucial for a proper diagnostic approach and patient work-up. This review summarizes the most relevant causes of infectious, inflammatory, vascular, and neoplastic disorders presenting as predominantly multiple focal non-cystic lesions.

Factors influencing referral to maternity models of care in Australian general practice.

BACKGROUND: In the Australian maternity system, general practitioners play a vital role in advising and directing prospective parents to maternity models of care. Optimising model of care discussions and the decision-making process avoids misaligning women with over or under specialised care, reduces the potential for disruptive care transitions and unnecessary healthcare costs, and is critical in ensuring consumer satisfaction. Current literature overwhelmingly focusses on women's decision-making around model of care discussions and neglects the gatekeeping role of the General Practitioner (GP). This study aimed to explore and describe the factors influencing Australian GPs decision-making when referring pregnant women to maternity models of care. METHODS: This study used a qualitative descriptive approach. General practitioners (N = 12) with experience referring women to maternity models of care in Australia participated in a semi-structured interview. Interviews occurred between October and November 2021 by telephone or videoconference. Reflexive thematic analysis was facilitated by NVivo-12 data management software to codify and interpret themes from the data. FINDINGS: Two broad themes were interpreted from the data. The first theme entitled 'GP Factors', incorporated three associated sub-themes including '1) GPs Previous Model of Care Experience', '2) Gaps in GP Knowledge' and '3) GP Perception of Models of Care'. The second theme, entitled 'Woman's Factors', encapsulated two associated sub-themes including the '4) Woman's Preferences' and '5) Access to Models'. CONCLUSIONS: This study provides novel evidence regarding general practitioner perspectives of the factors influencing model of care decision-making and referral. Predominant findings suggest that gaps in GP knowledge regarding the available models of care are present and are largely informed by prior personal and professional experience. Most GPs described referring to models of care they perceive positively and centring their model of care discussions on the woman's preferences and accessibility. The exploration and description of factors influencing model of care decisions provide unique insight into the ways that all stakeholders can experience access to a broader range of models of care including midwifery-led continuity of care models aligned with consumer-demand. In addition, the role of national primary health networks is outlined as a means to achieving this.

Functional analysis of phosphoethanolamine N-methyltransferase in plants and parasites: Essential S-adenosylmethionine-dependent methyltransferase in choline and phospholipid metabolism.

Phospholipids play an essential role as a barrier between cell content and the extracellular environment and regulate various cell signaling processes. Phosphatidylcholine (PtdCho) is one of the most abundant phospholipids in plant, animal, and some prokaryote cell membranes. In plants and some parasites, the biosynthesis of PtdCho begins with the amino acid serine, followed mainly through a phosphoethanolamine N-methyltransferase (PMT)-mediated biosynthetic pathway to phosphocholine (pCho). Because the PMT-mediated pathway, referred to as the phosphobase methylation pathway, produces a series of important primary and specialized metabolites for plant development and stress response, understanding the PMT enzyme is a key aspect of engineering plants with improved stress tolerance and fortified nutrients. Importantly, given the very limited phylogenetic distribution of PMTs, functional analysis and the identification of inhibitors targeting PMTs have potential and positive impacts in humans and in veterinary and agricultural fields. Here, we describe detailed basic knowledge and practical research methods to enable the systematic study of the biochemical and biophysical functions of PMT. The research methods described in this chapter are also applicable to the studies of other ubiquitous S-adenosyl-l-methionine (SAM)-dependent methyltransferases in all kingdoms.

Psychiatric Advance Directives as an Ethical Communication Tool: An Analysis of Definitions.

A psychiatric advance directive (PAD) is a communication tool that promotes patients' autonomy and gives capacitated adults who live with serious mental illnesses the ability to record their preferences for care and designate a proxy decision maker before a healthcare crisis. Despite a high degree of interest by patients and previous studies that recommend that clinicians facilitate the completion of PADs, the rate of implementation of PAD remains low. Research indicates that many clinicians lack the necessary experience to facilitate the completion of PADs and to use them, and, as a consequence, do not effectively engage patients about PADs. This study developed practical recommendations for clinicians to improve their ability to communicate and facilitate PADs. We (1) thematically analyzed definitions of PADs published in 118 articles across disciplines, and (2) presented our recommendations for enhanced communication in clinical practice that emphasizes patient-centeredness, usefulness, and clarity, aligned with evidence-based practices that put patients' autonomy and understanding first. While there is no one-size-fits-all script to engage patients in complex conversations, our recommended strategies include an emphasis on patients' autonomy, the adaptation of word choices, the use of metaphor not simile, and checking for patients' understanding as effective methods of clinical communication.

Identification of important factors in an inpatient fall risk prediction model to improve the quality of care using EHR and electronic administrative data: A machine-learning approach.

BACKGROUND: Inpatient falls, many resulting in injury or death, are a serious problem in hospital settings. Existing falls risk assessment tools, such as the Morse Fall Scale, give a risk score based on a set of factors, but don't necessarily signal which factors are most important for predicting falls. Artificial intelligence (AI) methods provide an opportunity to improve predictive performance while also identifying the most important risk factors associated with hospital-acquired falls. We can glean insight into these risk factors by applying classification tree, bagging, random forest, and adaptive boosting methods applied to Electronic Health Record (EHR) data. OBJECTIVE: The purpose of this study was to use tree-based machine learning methods to determine the most important predictors of inpatient falls, while also validating each via cross-validation. MATERIALS AND METHODS: A case-control study was designed using EHR and electronic administrative data collected between January 1, 2013 to October 31, 2013 in 14 medical surgical units. The data contained 38 predictor variables which comprised of patient characteristics, admission information, assessment information, clinical data, and organizational characteristics. Classification tree, bagging, random forest, and adaptive boosting methods were used to identify the most important factors of inpatient fall-risk through variable importance measures. Sensitivity, specificity, and area under the ROC curve were computed via ten-fold cross validation and compared via pairwise t-tests. These methods were also compared to a univariate logistic regression of the Morse Fall Scale total score. RESULTS: In terms of AUROC, bagging (0.89), random forest (0.90), and boosting (0.89) all outperformed the Morse Fall Scale (0.86) and the classification tree (0.85), but no differences were measured between bagging, random forest, and adaptive boosting, at a p-value of 0.05. History of Falls, Age, Morse Fall Scale total score, quality of gait, unit type, mental status, and number of high fall risk increasing drugs (FRIDs) were considered the most important features for predicting inpatient fall risk. CONCLUSIONS: Machine learning methods have the potential to identify the most relevant and novel factors for the detection of hospitalized patients at risk of falling, which would improve the quality of patient care, and to more fully support healthcare provider and organizational leadership decision-making. Nurses would be able to enhance their judgement to caring for patients at risk for falls. Our study may also serve as a reference for the development of AI-based prediction models of other iatrogenic conditions. To our knowledge, this is the first study to report the importance of patient, clinical, and organizational features based on the use of AI approaches.

Vitamin D status is associated with muscular strength in a nationally representative sample of US youth.

AIM: To evaluate the association between serum 25-hydroxyvitamin D (25OHD) and muscular strength in a nationally representative sample of US youth. METHODS: Participants (n = 3350) were 6- to 18-y-olds from 2011 to 2014 National Health and Nutrition Examination Survey. Relative handgrip strength was quantified using age- and sex-specific z-scores. Poor strength was defined as those <25th percentile. Multivariate general linear and logistic models were used to compare strength and poor strength status by clinically relevant groupings of 25OHD. RESULTS: Approximately 20.2% of youth had 25OHD <50 nmol/L. Mean relative strength was highest for those at ≥75 nmol/L of 25OHD. The percentage of boys/girls with poor strength in the <50 nmol/L, 50-74.9 nmol/L and ≥75 nmol/L groups was 34.9%/32.3%, 25.8%/28.2% and 14.0%/15.8%, respectively. The odds of boys and girls with <50 nmol/L 25OHD having poor strength were 2.8 (95% CI: 1.4, 5.5) and 3.4 (1.7, 6.8) times higher compared to those with ≥75 nmol/L, respectively. CONCLUSION: Higher levels of circulating vitamin D were associated with higher relative strength, and poor strength was more prevalent when 25OHD was <75 nmol/L. These findings highlight the value of vitamin D for the muscle-bone unit and potential extraskeletal ramifications.

How much bias results if a quasi-experimental design combines local comparison groups, a pretest outcome measure and other covariates?: A within study comparison of preschool effects.

This study uses a within study comparison design (WSC) to conduct a novel test of how much causal bias results when researchers use a nonequivalent comparison group design type (NECGD) that combines: (a) a comparison group local to the treatment group; (b) a pretest measure of the study outcome; and (c) a rich set of 19 other multidimensional covariates. Most prior WSCs have dealt with the bias consequences of only 1 of these, revealing that each routinely reduces bias but does not necessarily eliminate it. Thus, a need exists to identify NECGDs that more robustly eliminate bias. This study is the first to examine how combining the 3 bias-control mechanisms above affects bias. The intervention we examine is a prekindergarten mathematics curriculum, for which a randomized control trial (RCT) produces a positive 1-year math effect. Final bias in the NECGD is assessed as the difference between its impact and that of the RCT when each design has the same intervention, outcome, and estimand. Over the many specifications we explore, NECGD bias is less than .10 standard deviations, indicating that minimal bias results when an NECGD combines all 3 design elements. The factorial design we use in this study also tests the bias associated with seven other NECGD types. Comparing the total pattern of results shows that the minimal bias when all 3 elements are combined is uniquely attributable to the locally chosen comparison group and not the availability of a pretest or other covariates. In actual research practice, it is impossible to predict in advance which design elements will affect bias by how much in any given application. So further research is needed to probe whether the simultaneous use of all three design elements achieves minimal bias dependably across diverse applications and not just in the preschool math context examined here. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The Sequential Scale-Up of an Evidence-Based Intervention: A Case Study.

Policy makers face dilemmas when choosing a policy, program, or practice to implement. Researchers in education, public health, and other fields have proposed a sequential approach to identifying interventions worthy of broader adoption, involving pilot, efficacy, effectiveness, and scale-up studies. In this article, we examine a scale-up of an early math intervention to the state level, using a cluster randomized controlled trial. The intervention, Pre-K Mathematics, has produced robust positive effects on children's math ability in prior pilot, efficacy, and effectiveness studies. In the current study, we ask if it remains effective at a larger scale in a heterogeneous collection of pre-K programs that plausibly represent all low-income families with a child of pre-K age who live in California. We find that Pre-K Mathematics remains effective at the state level, with positive and statistically significant effects (effect size on the Early Childhood Longitudinal Study, Birth Cohort Mathematics Assessment = .30, p < .01). In addition, we develop a framework of the dimensions of scale-up to explain why effect sizes might decrease as scale increases. Using this framework, we compare the causal estimates from the present study to those from earlier, smaller studies. Consistent with our framework, we find that effect sizes have decreased over time. We conclude with a discussion of the implications of our study for how we think about the external validity of causal relationships.

Matched Comparison Group Design Standards in Systematic Reviews of Early Childhood Interventions.

BACKGROUND: Systematic reviews assess the quality of research on program effectiveness to help decision makers faced with many intervention options. Study quality standards specify criteria that studies must meet, including accounting for baseline differences between intervention and comparison groups. We explore two issues related to systematic review standards: covariate choice and choice of estimation method. OBJECTIVE: To help systematic reviews develop/refine quality standards and support researchers in using nonexperimental designs to estimate program effects, we address two questions: (1) How well do variables that systematic reviews typically require studies to account for explain variation in key child and family outcomes? (2) What methods should studies use to account for preexisting differences between intervention and comparison groups? METHODS: We examined correlations between baseline characteristics and key outcomes using Early Childhood Longitudinal Study-Birth Cohort data to address Question 1. For Question 2, we used simulations to compare two methods-matching and regression adjustment-to account for preexisting differences between intervention and comparison groups. RESULTS: A broad range of potential baseline variables explained relatively little of the variation in child and family outcomes. This suggests the potential for bias even after accounting for these variables, highlighting the need for systematic reviews to provide appropriate cautions about interpreting the results of moderately rated, nonexperimental studies. Our simulations showed that regression adjustment can yield unbiased estimates if all relevant covariates are used, even when the model is misspecified, and preexisting differences between the intervention and the comparison groups exist.

The Economic and Clinical Impact of Sustained Use of a Progressive Mobility Program in a Neuro-ICU.

OBJECTIVE: To investigate a progressive mobility program in a neurocritical care population with the hypothesis that the benefits and outcomes of the program (e.g., decreased length of stay) would have a significant positive economic impact. DESIGN: Retrospective analysis of economic and clinical outcome data before, immediately following, and 2 years after implementation of the Progressive Upright Mobility Protocol Plus program (UF Health Shands Hospital, Gainesville, FL) involving a series of planned movements in a sequential manner with an additional six levels of rehabilitation in the neuro-ICU at UF Health Shands Hospital. SETTING: Thirty-bed neuro-ICU in an academic medical center. PATIENTS: Adult neurologic and neurosurgical patients: 1,118 patients in the pre period, 731 patients in the post period, and 796 patients in the sustained period. INTERVENTIONS: Implementation of Progressive Upright Mobility Protocol Plus. MEASUREMENTS AND MAIN RESULTS: ICU length of stay decreased from 6.5 to 5.8 days in the immediate post period and 5.9 days in the sustained period (F(2,2641) = 3.1; p = 0.045). Hospital length of stay was reduced from 11.3 ± 14.1 days to 8.6 ± 8.8 post days and 8.8 ± 9.3 days sustained (F(2,2641) = 13.0; p < 0.001). The impact of the study intervention on ICU length of stay (p = 0.031) and hospital length of stay (p < 0.001) remained after adjustment for age, sex, diagnoses, sedation, and ventilation. Hospital-acquired infections were reduced by 50%. Average total cost per patient after adjusting for inflation was significantly reduced by 16% (post period) and 11% (sustained period) when compared with preintervention (F(2,2641) = 3.1; p = 0.045). Overall, these differences translated to an approximately $12.0 million reduction in direct costs from February 2011 through the end of 2013. CONCLUSIONS: An ongoing progressive mobility program in the neurocritical care population has clinical and financial benefits associated with its implementation and should be considered.

A Trusted Source of Information: How Systematic Reviews Can Support User Decisions About Adopting Evidence-Based Programs.

BACKGROUND: Systematic reviews sponsored by federal departments or agencies play an increasingly important role in disseminating information about evidence-based programs and have become a trusted source of information for administrators and practitioners seeking evidence-based programs to implement. These users vary in their knowledge of evaluation methods and their ability to interpret systematic review findings. They must consider factors beyond program effectiveness when selecting an intervention, such as the relevance of the intervention to their target population, community context, and service delivery system; readiness for replication and scale-up; and the ability of their service delivery system or agency to implement the intervention. OBJECTIVE: To support user decisions about adopting evidence-based practices, this article discusses current systematic review practices and alternative approaches to synthesizing and presenting findings and providing information. METHOD: We reviewed the publicly available information on review methodology and findings for eight federally funded systematic reviews in the labor, education, early childhood, mental health/substance abuse, family support, and criminal justice topic areas. CONCLUSION: The eight federally sponsored evidence reviews we examined all provide information that can help users to interpret findings on evidence of effectiveness and to make adoption decisions. However, they are uneven in the amount, accessibility, and consistency of information they report. For all eight reviews, there is room for improvement in supporting users' adoption decisions through more detailed, accessible, and consistent information in these areas.

External Validity: The Next Step for Systematic Reviews?

BACKGROUND: Systematic reviews-which identify, assess, and summarize existing research-are usually designed to determine whether research shows that an intervention has evidence of effectiveness, rather than whether an intervention will work under different circumstances. The reviews typically focus on the internal validity of the research and do not consistently incorporate information on external validity into their conclusions. OBJECTIVES: In this article, we focus on how systematic reviews address external validity. METHODS: We conducted a brief scan of 19 systematic reviews and a more in-depth examination of information presented in a systematic review of home visiting research. RESULTS: We found that many reviews do not provide information on generalizability, such as statistical representativeness, but focus on factors likely to increase heterogeneity (e.g., numbers of studies or settings) and report on context. The latter may help users decide whether the research characteristics-such as sample demographics or settings-are similar to their own. However, we found that differences in reporting, such as which variables are included and how they are measured, make it difficult to summarize across studies or make basic determinations of sample characteristics, such as whether the majority of a sample was unemployed or married. CONCLUSION: Evaluation research and systematic reviews would benefit from reporting guidelines for external validity to ensure that key information is reported across studies.

Differential responses of plasmacytoid dendritic cells to influenza virus and distinct viral pathogens.

UNLABELLED: Plasmacytoid dendritic cells (pDCs) are key components of the innate immune response that are capable of synthesizing and rapidly releasing vast amounts of type I interferons (IFNs), particularly IFN-α. Here we investigated whether pDCs, often regarded as a mere source of IFN, discriminate between various functionally discrete stimuli and to what extent this reflects differences in pDC responses other than IFN-α release. To examine the ability of pDCs to differentially respond to various doses of intact and infectious HIV, hepatitis C virus, and H1N1 influenza virus, whole-genome gene expression analysis, enzyme-linked immunosorbent assays, and flow cytometry were used to investigate pDC responses at the transcriptional, protein, and cellular levels. Our data demonstrate that pDCs respond differentially to various viral stimuli with significant changes in gene expression, including those involved in pDC activation, migration, viral endocytosis, survival, or apoptosis. In some cases, the expression of these genes was induced even at levels comparable to that of IFN-α. Interestingly, we also found that depending on the viral entity and the viral titer used for stimulation, induction of IFN-α gene expression and the actual release of IFN-α are not necessarily temporally coordinated. In addition, our data suggest that high-titer influenza A (H1N1) virus infection can stimulate rapid pDC apoptosis. IMPORTANCE: Plasmacytoid dendritic cells (pDCs) are key players in the viral immune response. With the host response to viral infection being dependent on specific virus characteristics, a thorough examination and comparison of pDC responses to various viruses at various titers is beneficial for the field of virology. Our study illustrates that pDC infection with influenza virus, HIV, or hepatitis C virus results in a unique and differential response to each virus. These results have implications for future virology research, vaccine development, and virology as a whole.

Melanoma NOS1 expression promotes dysfunctional IFN signaling.

In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

Gene expression profiling in acute allograft rejection: challenging the immunologic constant of rejection hypothesis.

In humans, the role and relationship between molecular pathways that lead to tissue destruction during acute allograft rejection are not fully understood. Based on studies conducted in humans, we recently hypothesized that different immune-mediated tissue destruction processes (i.e. cancer, infection, autoimmunity) share common convergent final mechanisms. We called this phenomenon the "Immunologic Constant of Rejection (ICR)." The elements of the ICR include molecular pathways that are consistently described through different immune-mediated tissue destruction processes and demonstrate the activation of interferon-stimulated genes (ISGs), the recruitment of cytotoxic immune cells (primarily through CXCR3/CCR5 ligand pathways), and the activation of immune effector function genes (IEF genes; granzymes A/B, perforin, etc.). Here, we challenge the ICR hypothesis by using a meta-analytical approach and systematically reviewing microarray studies evaluating gene expression on tissue biopsies during acute allograft rejection. We found the pillars of the ICR consistently present among the studies reviewed, despite implicit heterogeneity. Additionally, we provide a descriptive mechanistic overview of acute allograft rejection by describing those molecular pathways most frequently encountered and thereby thought to be most significant. The biological role of the following molecular pathways is described: IFN-γ, CXCR3/CCR5 ligand, IEF genes, TNF-α, IL-10, IRF-1/STAT-1, and complement pathways. The role of NK cell, B cell and T-regulatory cell signatures are also addressed.