Molecular Diversity Assessment using Chemotypes.

BACKGROUND: Many techniques to design chemical libraries for screening have been put forward over time. General use libraries are still important when screening against novel targets, and their design has relied on the use of molecular descriptors. In contrast, chemotype or scaffold analysis has been used less often. OBJECTIVE: We describe a simple method to assess chemical diversity based on counts of the chemotypes that offers an alternative to model chemical diversity. We describe a simple method to assess chemical diversity based on counts of the chemotypes that offers an alternative to model chemical diversity based on computed molecular properties. We show how chemotype counts can be used to evaluate the diversity of a library and compare diversity selection algorithms. We demonstrate an efficient compound selection algorithm based on chemotype analysis. METHODS: We use automated chemotype perception algorithms and compare them to traditional techniques for diversity analysis to check their effectiveness in designing diverse libraries for screening. RESULTS: The best type of molecular fingerprints for diversity selection in our analysis are extended circular fingerprints, but they can be outperformed by the use of a chemotype diversity algorithm, which can be more intuitive than traditional techniques based on molecular descriptors. Chemotype- -based algorithms retrieve a larger share of the chemotypes contained in a library when picking a subset of the chemicals in a collection. CONCLUSIONS: Chemotype analysis offers an alternative for the generation of a general-purpose screening library as it maximizes the number of chemotypes present in a subset with the smallest number of compounds. The applications of methods based on chemotype analysis that does not resort to the use of molecular descriptors are a very promising but seldom explored area of chemoinformatics.

A photometric stereo-based 3D imaging system using computer vision and deep learning for tracking plant growth.

BACKGROUND: Tracking and predicting the growth performance of plants in different environments is critical for predicting the impact of global climate change. Automated approaches for image capture and analysis have allowed for substantial increases in the throughput of quantitative growth trait measurements compared with manual assessments. Recent work has focused on adopting computer vision and machine learning approaches to improve the accuracy of automated plant phenotyping. Here we present PS-Plant, a low-cost and portable 3D plant phenotyping platform based on an imaging technique novel to plant phenotyping called photometric stereo (PS). RESULTS: We calibrated PS-Plant to track the model plant Arabidopsis thaliana throughout the day-night (diel) cycle and investigated growth architecture under a variety of conditions to illustrate the dramatic effect of the environment on plant phenotype. We developed bespoke computer vision algorithms and assessed available deep neural network architectures to automate the segmentation of rosettes and individual leaves, and extract basic and more advanced traits from PS-derived data, including the tracking of 3D plant growth and diel leaf hyponastic movement. Furthermore, we have produced the first PS training data set, which includes 221 manually annotated Arabidopsis rosettes that were used for training and data analysis (1,768 images in total). A full protocol is provided, including all software components and an additional test data set. CONCLUSIONS: PS-Plant is a powerful new phenotyping tool for plant research that provides robust data at high temporal and spatial resolutions. The system is well-suited for small- and large-scale research and will help to accelerate bridging of the phenotype-to-genotype gap.

The Reliability of Disease Activity Score in 28 Joints-C-Reactive Protein Might Be Overestimated in a Subgroup of Rheumatoid Arthritis Patients, When the Score Is Solely Based on Subjective Parameters: A Cross-sectional, Exploratory Study.

BACKGROUND: Disease Activity Score in 28 Joints (DAS28) is a scoring system to evaluate disease activity and treatment response in rheumatoid arthritis (RA). A DAS28 score of greater than 3.2 is a well-described limit for treatment intensification; however, the reliability of DAS28 might be overestimated. OBJECTIVE: The aim of this study was to evaluate the reliability of DAS28 in RA, especially focusing on a subgroup of patients with a DAS28 score of greater than 3.2. METHODS: Data from RA patients registered in the local part of Danish DANBIO Registry were collected in May 2015. Patients were categorized into 2 groups: First, those with DAS28 >3.2 with at least one swollen joint (SJ) or elevated C-reactive protein (CRP) ("objective group"), and second, patients with a DAS28 >3.2 who had no SJ, and CRP values were within the reference range ("subjective group"). Disease Activity Score in 28 Joints, Clinical Disease Activity Index, and Health Assessment Questionnaire scores were calculated for each group. We defined new score, DAS28 subjective, to focus on subjective parameters. RESULTS: Two hundred thirty patients were included; 198 (86.1%) and 32 (13.9%) patients were in the objective and subjective groups, respectively. Patients in the subjective group had lower mean values of DAS28 (P < 0.001) and Evaluator Global Assessment (P < 0.001) with less common immunoglobulin M rheumatoid factor (P < 0.001) and anti-cyclic citrullinated peptide positivity (P = 0.02) and contrarily higher mean values of tender joints (P = 0.04) and DAS28 based on subjective parameters (P = 0.003) compared with the objective group. CONCLUSIONS: Rheumatoid arthritis scoring systems should be used cautiously in patients who are considered for treatment intensification. Patients with central sensitization and psychological problems and those with false-positive diagnosis of RA are at high risk of overtreatment.

Financially efficient cataract surgery in today's healthcare environment.

PURPOSE OF REVIEW: To review the literature and create a concise evaluation and comment on the ways to provide financially efficient cataract surgery in a healthcare environment that produces significant challenges to providing care, while maintaining quality outcomes, safety, patient satisfaction, and employee satisfaction. RECENT FINDINGS: The recent reductions in reimbursement for cataract surgery have fueled an increased need to drive innovation in ways to be more financially efficient. At the same time, new technology in the field, especially as it relates to use of the femtosecond laser for portions of lens surgery, has increased the challenges in creating an efficient and cost-effective structure for providing care. SUMMARY: Cataract surgery is one of the most beneficial procedures for a patient's quality of life, and is one of the most common surgical procedures performed. At the same time, the current cost-effectiveness is quite high, and yet there are still ways to become more financially efficient in many centers providing cataract care.

Diagnostic performance and cost of CT angiography versus stress ECG--a randomized prospective study of suspected acute coronary syndrome chest pain in the emergency department (CT-COMPARE).

BACKGROUND: Coronary CT angiography (CCTA) has high sensitivity, with 3 recent randomized trials favorably comparing CCTA to standard-of-care. Comparison to exercise stress ECG (ExECG), the most available and least expensive standard-of-care worldwide, has not been systematically tested. METHODS: CT-COMPARE was a randomized, single-center trial of low-intermediate risk chest pain subjects undergoing CCTA or ExECG after the first negative troponin. From March 2010 to April 2011, 562 patients randomized to either dual-source CCTA (n=322) or ExECG (n=240). Primary endpoints were diagnostic performance for ACS, and hospital cost at 30 days. Secondary endpoints were time-to-discharge, admission rates, and downstream resource utilization. RESULTS: ACS occurred in 24 (4%) patients. ExECG had 213 negative studies and 27 (26%) positive studies for ACS with sensitivity of 83% [95% CI: 36, 99.6%], specificity of 91% [CI: 86, 94%], and ROC AUC of 0.87 [CI: 0.70, 1]. CCTA (>50% stenosis considered positive) had 288 negative studies and 18/35 (51%) positive studies with a sensitivity of 100% [CI: 81.5, 100], specificity of 94% [CI: 91.2, 96.7%], and ROC of 0.97 [CI: 0.92, 1.0; p=0.2]. Despite CCTA having higher odds of downstream testing (OR 2.0), 30 day per-patient cost was significantly lower for CCTA ($2193 vs $2704, p<0.001). Length of stay for CCTA was significantly reduced (13.5h [95% CI: 11.2-15.7], ExECG 19.7h [95% CI: 17.4-22.1], p<0.0005), which drove the reduction in cost. No patient had post-discharge cardiovascular events at 30 days. CONCLUSIONS: CCTA had improved diagnostic performance compared to ExECG, combined with 35% relative reduction in length-of-stay, and 20% reduction in hospital costs. These data lend further evidence that CCTA is useful as a first line assessment in emergency department chest pain.

The PROMIS Smoking Initiative: initial validity evidence for six new smoking item banks.

INTRODUCTION: The Patient-Reported Outcomes Measurement Information System (PROMIS) Smoking Initiative has developed 6 item banks for assessing smoking behaviors and biopsychosocial correlates of smoking among daily and nondaily adult cigarette smokers. This paper presents descriptive information and preliminary validity evidence for the item banks (Nicotine Dependence, Coping Expectancies, Emotional and Sensory Expectancies, Health Expectancies, Psychosocial Expectancies, and Social Motivations). METHODS: Using data from a large sample of daily (N = 4,201) and nondaily (N = 1,183) smokers, we generated mean daily and nondaily smoking bank scores according to select demographic groups. We also examined correlations among the 6 banks and examined the associations of bank scores with smoking behavior items (e.g., quantity of smoking, interest in quitting) and select health-related quality of life measures (i.e., physical functioning, anxiety, alcohol consumption). RESULTS: Correlations among the 6 banks are moderate (daily mean r = .48, range = .04-.80; nondaily mean r = .47, range = .12-.75). The pattern of associations between bank scores and other measures provides validity evidence for the bank domains (e.g., nicotine dependence is most strongly associated with smoking quantity and time to first cigarette of the day; health and psychosocial expectancies are most related to quitting recency and interest; coping expectancies are strongly associated with anxiety). CONCLUSIONS: These analyses provide useful descriptive information about the 6 smoking item banks as well as preliminary evidence for their validity. Independent sample data are currently being collected to replicate these findings, to establish test-retest reliability, and to develop crosswalks to existing smoking measures (e.g., nicotine dependence to Fagerström Test for Nicotine Dependence). Future research will also evaluate the bank scores' sensitivity to change.

Limited-information goodness-of-fit testing of hierarchical item factor models.

In applications of item response theory, assessment of model fit is a critical issue. Recently, limited-information goodness-of-fit testing has received increased attention in the psychometrics literature. In contrast to full-information test statistics such as Pearson's X(2) or the likelihood ratio G(2) , these limited-information tests utilize lower-order marginal tables rather than the full contingency table. A notable example is Maydeu-Olivares and colleagues'M2 family of statistics based on univariate and bivariate margins. When the contingency table is sparse, tests based on M2 retain better Type I error rate control than the full-information tests and can be more powerful. While in principle the M2 statistic can be extended to test hierarchical multidimensional item factor models (e.g., bifactor and testlet models), the computation is non-trivial. To obtain M2 , a researcher often has to obtain (many thousands of) marginal probabilities, derivatives, and weights. Each of these must be approximated with high-dimensional numerical integration. We propose a dimension reduction method that can take advantage of the hierarchical factor structure so that the integrals can be approximated far more efficiently. We also propose a new test statistic that can be substantially better calibrated and more powerful than the original M2 statistic when the test is long and the items are polytomous. We use simulations to demonstrate the performance of our new methods and illustrate their effectiveness with applications to real data.

Potential clinical impact of cardiovascular magnetic resonance assessment of ejection fraction on eligibility for cardioverter defibrillator implantation.

BACKGROUND: For the primary prevention of sudden cardiac death, guidelines provide left ventricular ejection fraction (EF) criteria for implantable cardioverter defibrillator (ICD) placement without specifying the technique by which it should be measured. We sought to investigate the potential impact of performing cardiovascular magnetic resonance (CMR) for EF on ICD eligibility. METHODS: The study population consisted of patients being considered for ICD implantation who were referred for EF assessment by CMR. Patients who underwent CMR within 30 days of echocardiography were included. Echocardiographic EF was determined by Simpson's biplane method and CMR EF was measured by Simpson's summation of discs method. RESULTS: Fifty-two patients (age 62±15 years, 81% male) had a mean EF of 38 ± 14% by echocardiography and 35 ± 14% by CMR. CMR had greater reproducibility than echocardiography for both intra-observer (ICC, 0.98 vs 0.94) and inter-observer comparisons (ICC 0.99 vs 0.93). The limits of agreement comparing CMR and echocardiographic EF were - 16 to +10 percentage points. CMR resulted in 11 of 52 (21%) and 5 of 52 (10%) of patients being reclassified regarding ICD eligibility at the EF thresholds of 35 and 30% respectively. Among patients with an echocardiographic EF of between 25 and 40%, 9 of 22 (41%) were reclassified by CMR at either the 35 or 30% threshold. Echocardiography identified only 1 of the 6 patients with left ventricular thrombus noted incidentally on CMR. CONCLUSIONS: CMR resulted in 21% of patients being reclassified regarding ICD eligibility when strict EF criteria were used. In addition, CMR detected unexpected left ventricular thrombus in almost 10% of patients. Our findings suggest that the use of CMR for EF assessment may have a substantial impact on management in patients being considered for ICD implantation.

Pilot study of impact of medical-legal partnership services on patients' perceived stress and wellbeing.

UNLABELLED: Medical-legal partnerships (MLPs) bring legal services into health care settings to address patients' unmet legal needs. This pilot project examined whether MLP services impact patients' perceptions of stress and wellbeing. METHODS: Providers referred patients with legal concerns to the Tucson Family Advocacy Program (TFAP), an MLP within a family medicine clinic. Stress levels and wellbeing were assessed before and after legal services using self-administered 10-item Perceived Stress Scale (PSS-10) and Measure Yourself Concerns and Wellbeing (MYCaW) instruments. RESULTS: Sixty-seven participants completed pre- and post-service questionnaires. Within this group, the mean PSS-10 score decreased 8.1 points. Wellbeing scores improved by 1.8 points. Individual changes in perceived stress were strongly related to participants' level of concern regarding the particular legal issues addressed. CONCLUSIONS: Services in patient-centered medical homes to address unmet legal needs have the potential to reduce perceived stress and improve overall wellbeing. Additional studies concerning MLPs and patient outcomes are needed.

Medical-legal partnerships: transforming primary care by addressing the legal needs of vulnerable populations.

Health care is undermined when patients don't receive the benefit of laws intended to address social determinants of health, such as housing and food. Medical-legal partnerships, which now exist in more than 200 clinical sites in the United States, integrate lawyers into health care to address legal problems that create and perpetuate poor health. This paper describes how such medical-legal partnerships can change clinical systems--for example, by adding legal form letters to electronic health records to help low-income patients rectify substandard housing conditions. We recommend the integration of medical-legal partnerships into federal health care programs.

The value of dual-source 64-slice CT coronary angiography in the assessment of patients presenting to an acute chest pain service.

BACKGROUND: The absence of radiological evidence of plaque on computed tomographic coronary angiography (CTCA) reliably excludes obstructive coronary artery disease. METHODS: We studied patients who presented to our emergency department with chest pain and were admitted to our chest pain assessment service. If they were free of pain and without high-risk features of myocardial ischaemia including elevation of serum biomarkers they underwent CTCA and performed a standard treadmill exercise test. RESULTS: Eighty-nine patients aged 56.3+/-8.6 years were admitted. Eleven of them had selective angiography; CTCA identified all who had obstructive disease. More than half of the 85 patients who had normal values of cardiac troponin and of the 75 with a negative exercise test had radiological evidence of disease. During follow-up for 355+/-72 days none died, suffered myocardial infarction or required coronary artery surgery: two with obstructive disease underwent percutaneous coronary intervention 1 and 7 days after the index study. CONCLUSIONS: The CTCA findings were significantly correlated with those of selective angiography and with troponin status and increased the ascertainment of coronary artery disease in a cohort of patients at low risk for clinically significant ischaemic heart disease.

Assessment of midcarpal deformity of the wrist using the triangulation method.

PURPOSE: The purpose of this study is to present an alternative method for static radiologic assessment of the wrist for midcarpal instability (ie, palmar intercalated segmental instability [PISI] and dorsal intercalated segmental instability [DISI]). The triangulation method uses 3 anatomic landmarks observed on the standard lateral x-ray of the wrist. METHODS: A total of 125 normal lateral radiographs were measured to determine the normal range for the dorsal limb (DL) to palmar limb (PL) ratio. A 2-step process of performing triangulation is described. The first step is nonspecific screening of the radiograph and defines values greater than 1.0 as having a DISI deformity and values less than 0.5 as having a PISI deformity. The second step is used only for borderline values, which takes the position of the wrist into consideration and uses a normagram (reference chart) to match the DL:PL ratio with the radiometacarpal (RM) angle. RESULTS: The average lateral wrist position was 8.4 degrees of extension (-8.4). The average DL:PL ratio was 0.75 +/- 0.09 (range, 0.93-0.57). CONCLUSIONS: Based on these data we defined DISI deformity of the wrist as DL:PL ratios greater than 1.0, and ratios less than 0.5 representing PISI deformities. The triangulation method of assessing midcarpal alignment of the carpus is a practical and simple alternative to the traditional static radiologic method of assessing midcarpal instability of the wrist.