Long-Term Stability and Efficacy of NCT Solutions.

To realize the potential for the use of N-chlorotaurine (NCT) in healthcare, a better understanding of the long-term stability of the compound in water is needed. An array of analytical procedures is required that can measure changes in NCT concentration over time and allow for the detection and identification of contaminants and likely degradation end products. We used UV-Vis and NMR spectroscopy, HPLC, and LCMS to establish the stability of NCT in solutions subjected to prolonged ambient and elevated temperatures. Stability proved to be dependent on concentration with half-lives of ~120 days and ~236 days for 1% and 0.5% solutions of NCT at ~20 °C. Regardless of initial pH, all solutions shifted toward and maintained a pH of ~8.3 at 20 °C and 40 °C. NCT at 500 µg/mL and 250 µg /mL inhibited biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus but did not disperse established biofilms. NCT exposure to the biofilms had profound effects on the viability of both bacteria, reducing live organisms by >90%. Exposure of Interleukin-6 (IL-6) to 11 µM NCT reduced the binding of IL-6 to an immobilized specific antibody by ~48%, which is 5× the amount required for HOCl to bring about the same effect in this test system. Our data demonstrate the potency of the compound as an antimicrobial agent with potential benefits in the management of infected chronic wounds and suggest that NCT may contribute to anti-inflammatory processes in vivo by direct modification of cytokine mediators.

Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem.

Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.

Post-thaw ATP supplementation enhances cryoprotective effect of iodixanol in rat spermatozoa.

BACKGROUND: Successful cryopreservation of rat spermatozoa from various strains still remains a challenge. The objective of this study was to determine if combinations of OptiPrep™ (iodixanol) and adenosine 5'-triphosphate (ATP) can improve rat sperm function during the cryopreservation procedure. METHODS: Epididymal rat spermatozoa were frozen under different OptiPrep™ concentrations (0, 1, 2, 3 or 4 %) and were diluted with media supplemented with or without 2 mM ATP after thawing. Post-thaw sperm motility, acrosomal membrane integrity (AMI) and mitochondrial membrane potential (MMP) were then evaluated. In addition, the effect of different OptiPrep™ concentrations on fresh and cooled rat spermatozoa was tested via motility. RESULTS: There was no effect of OptiPrep™ on motility of fresh and cooled spermatozoa. The supplementation of 1 and 2 % OptiPrep™ increased motility of frozen spermatozoa at 10 min after thawing, while it did not improve motility of spermatozoa at 3 h after thawing in the absence of ATP. During incubation of thawed spermatozoa, the ATP addition protected time-dependent decrease in motility after thawing in OptiPrep™-treated samples. OptiPrep™ had no effect on AMI and MMP in frozen-thawed spermatozoa but combinations of OptiPrep™ and ATP improved MMP in frozen-thawed spermatozoa. CONCLUSIONS: Iodixanol has cryoprotective effects during rat sperm freezing without any toxic effect. Moreover, the combinations of iodixanol and ATP have a beneficial role in maintaining function of frozen-thawed rat spermatozoa for long period of incubation post-thaw.

The effects of regulation and litigation on a large for-profit nursing home chain.

This article examines the effects of state regulation and civil class action litigation on corporate compliance with nurse staffing and quality standards, corporate strategies to manage staffing and quality, and corporate financial status of a large for-profit nursing home chain. A historical case study was used to examine multiple public data sources, focusing on facilities in California from 2003 to 2011 during and after regulatory actions and litigation. The results showed that the state issued numerous deficiencies for violations of the nurse staffing and quality standards with minimal impact on quality compliance with state law. A class action jury trial found that the chain violated the state's minimum staffing standard on one-third of the total days during a six-year period and awarded a $677 million verdict. A court settlement and supervised injunction resulted in compliance with minimum staffing and some improvement in quality measures, but quality levels remained below the average California facilities. The litigation also had some negative financial impact on Skilled Healthcare Group's California facilities and parent company. Civil litigation had more impact on the chain than the regulatory oversight.

Development of an online tool to support financial and legal planning in dementia.

Objective: To develop, assess, and refine an online educational tool, Plan for Clarity, to support financial and legal planning in dementia. Methods: A Delphi mixed-method study with three rounds of anonymous review by lay and professional stakeholders was designed to reach consensus about the content of the online tool and explore the socio-cultural and behavioral factors that could affect access and use. Results: Consensus showed that the online tool covered key information, knowledge, and communication skills for financial and legal planning. Study themes: 1) the online tool had to be easy to navigate with relevant, easily understood information; 2) people with early signs of memory difficulties would be able to use the tool; 3) a referral from a trusted source is a primary way to facilitate access and use of the tool; and 4) discussions about financial and legal issues should be held early, ahead of barriers that can block discussion. Conclusion: These data suggest this online tool is relevant and feasible for dementia care and support as well as aging more generally. Innovation: Plan for Clarity is innovative as an evidence and theory-driven online education tool to address financial and legal planning for dementia care, particularly among underserved older adults.

Contact-independent exposure to Rhodococcus rhodochrous DAP96253 volatiles does not improve the survival rate of Myotis lucifugus (little brown bats) affected by White-nose Syndrome.

Since the emergence of White-nose Syndrome, a fungal disease in bats, caused by Pseudogymnoascus destructans, hibernating populations of little brown bats (Myotis lucifugus) have declined by 70-90% within P. destructans positive hibernacula. To reduce the impact of White-nose Syndrome to North American little brown bat populations we evaluated if exposure to volatile organic compounds produced by induced cells from Rhodococcus rhodochrous strain DAP96253 could improve the overwinter survival of bats infected by P. destructans. Two simultaneous field treatment trials were conducted at natural hibernacula located in Rockcastle and Breckinridge counties, Kentucky, USA. A combined total of 120 little brown bats were randomly divided into control groups (n = 60) which were not exposed to volatile organic compounds and treatment groups (n = 60) which were exposed to volatile organic compounds produced by non-growth, fermented cell paste composed of R. rhodochrous strain DAP96253 cells. Cox proportional hazard models revealed a significant decreased survival at the Rockcastle field trial site but not the Breckinridge field site. At the Breckinridge hibernacula, overwinter survival for both treatment and control groups were 60%. At the Rockcastle hibernacula, Kaplan-Meier survival curves indicated significantly increased overwinter survival of bats in the control group (43% survived) compared to the treatment group (20% survived). Although complete inhibition of P. destructans by volatile organic compounds produced by induced R. rhodochrous strain DAP96253 cells was observed in vitro studies, our results suggest that these volatile organic compounds do not inhibit P. destructans in situ and may promote P. destructans growth.

Using Machine Learning in Veterinary Medical Education: An Introduction for Veterinary Medicine Educators.

Machine learning (ML) offers potential opportunities to enhance the learning, teaching, and assessments within veterinary medical education including but not limited to assisting with admissions processes as well as student progress evaluations. The purpose of this primer is to assist veterinary educators in appraising and potentially adopting these rapid upcoming advances in data science and technology. In the first section, we introduce ML concepts and highlight similarities/differences between ML and classical statistics. In the second section, we provide a step-by-step worked example using simulated veterinary student data to answer a hypothesis-driven question. Python syntax with explanations is provided within the text to create a random forest ML prediction model, a model composed of decision trees with each decision tree being composed of nodes and leaves. Within each step of the model creation, specific considerations such as how to manage incomplete student records are highlighted when applying ML algorithms within the veterinary education field. The results from the simulated data demonstrate how decisions by the veterinary educator during ML model creation may impact the most important features contributing to the model. These results highlight the need for the veterinary educator to be fully transparent during the creation of ML models and future research is needed to establish guidelines for handling data not missing at random in medical education, and preferred methods for model evaluation.

Health research in academic health systems: time for a new model.

Research, along with patient care and education, is a core element of the academic health system's tripartite mission; it is essential to the academic health system's societal commitment to advancing the public's health. Research at academic health systems in the United States is increasingly resource-constrained and, in important ways, the underlying financial model supporting it has reached a point of unsustainability. This commentary reviews the roles that health research at academic health systems plays in society, describes the ways in which the current model of health research is under strain, and proposes an evolved model and series of organizational and operational steps to consider in moving health research forward.

Hospital-Based Medical-Legal Partnerships for Complex Care Patients: Intersectionality and Ethics Considerations.

Health systems are integrating medical-legal partnerships (MLPs) into clinical care and increasingly center "complex care" patients. These patients have intersecting medical and social needs and often face systemic inequities that exacerbate their chronic health conditions. This paper describes a role for MLPs in hospital quality initiatives; examines the ethics of MLPs assisting with guardianship and institutionalization of hospital patients including marginalized groups; and advocates for MLP interventions designed to address intersectional and ethical concerns.

Evaluating semi-supervision methods for medical image segmentation: applications in cardiac magnetic resonance imaging.

Purpose: Neural networks have potential to automate medical image segmentation but require expensive labeling efforts. While methods have been proposed to reduce the labeling burden, most have not been thoroughly evaluated on large, clinical datasets or clinical tasks. We propose a method to train segmentation networks with limited labeled data and focus on thorough network evaluation. Approach: We propose a semi-supervised method that leverages data augmentation, consistency regularization, and pseudolabeling and train four cardiac magnetic resonance (MR) segmentation networks. We evaluate the models on multiinstitutional, multiscanner, multidisease cardiac MR datasets using five cardiac functional biomarkers, which are compared to an expert's measurements using Lin's concordance correlation coefficient (CCC), the within-subject coefficient of variation (CV), and the Dice coefficient. Results: The semi-supervised networks achieve strong agreement using Lin's CCC ( > 0.8 ), CV similar to an expert, and strong generalization performance. We compare the error modes of the semi-supervised networks against fully supervised networks. We evaluate semi-supervised model performance as a function of labeled training data and with different types of model supervision, showing that a model trained with 100 labeled image slices can achieve a Dice coefficient within 1.10% of a network trained with 16,000+ labeled image slices. Conclusion: We evaluate semi-supervision for medical image segmentation using heterogeneous datasets and clinical metrics. As methods for training models with little labeled data become more common, knowledge about how they perform on clinical tasks, how they fail, and how they perform with different amounts of labeled data is useful to model developers and users.

Challenges and Opportunities for Clinician Implicit Bias Training: Insights from Perinatal Care Stakeholders.

Introduction: In an attempt to address health inequities, many U.S. states have considered or enacted legislation requiring antibias or implicit bias training (IBT) for health care providers. California's "Dignity in Pregnancy and Childbirth Act" requires that hospitals and alternative birthing centers provide IBT to perinatal clinicians with the goal of improving clinical outcomes for Black women and birthing people. However, there is as yet insufficient evidence to identify what IBT approaches, if any, achieve this goal. Engaging the experiences and insights of IBT stakeholders is a foundational step in informing nascent IBT policy, curricula, and implementation. Methods: We conducted a multimethod community-based participatory research study with key stakeholders of California's IBT policy to identify key challenges and recommendations for effective clinician IBT. We used focus groups, in-depth interviews, combined inductive/deductive thematic analysis, and multiple techniques to promote rigor and validity. Participants were San Francisco Bay Area-based individuals who identified as Black or African American women with a recent hospital birth (n=20), and hospital-based perinatal clinicians (n=20). Results: We identified numerous actionable challenges and recommendations regarding aspects of (1) state law; (2) IBT content and format; (3) health care facility IBT implementation; (4) health care facility environment; and (5) provider commitment and behaviors. Patient and clinician insights overlapped substantially. Many respondents felt IBT would improve outcomes only in combination with other antiracism interventions. Health Equity Implications: These stakeholder insights offer policy-makers, health system leaders, and curriculum developers crucial guidance for the future development and implementation of clinician antibias interventions.

Lost in translation: the unintended consequences of advance directive law on clinical care.

BACKGROUND: Advance directive law may compromise the clinical effectiveness of advance directives. PURPOSE: To identify unintended legal consequences of advance directive law that may prevent patients from communicating end-of-life preferences. DATA SOURCES: Advance directive legal statutes for all 50 U.S. states and the District of Columbia and English-language searches of LexisNexis, Westlaw, and MEDLINE from 1966 to August 2010. STUDY SELECTION: Two independent reviewers selected 51 advance directive statutes and 20 articles. Three independent legal reviewers selected 105 legal proceedings. DATA EXTRACTION: Two reviewers independently assessed data sources and used critical content analysis to determine legal barriers to the clinical effectiveness of advance directives. Disagreements were resolved by consensus. DATA SYNTHESIS: Legal and content-related barriers included poor readability (that is, laws in all states were written above a 12th-grade reading level), health care agent or surrogate restrictions (for example, 40 states did not include same-sex or domestic partners as default surrogates), and execution requirements needed to make forms legally valid (for example, 35 states did not allow oral advance directives, and 48 states required witness signatures, a notary public, or both). Vulnerable populations most likely to be affected by these barriers included patients with limited literacy, limited English proficiency, or both who cannot read or execute advance directives; same-sex or domestic partners who may be without legally valid and trusted surrogates; and unbefriended, institutionalized, or homeless patients who may be without witnesses and suitable surrogates. LIMITATION: Only appellate-level legal cases were available, which may have excluded relevant cases. CONCLUSION: Unintended negative consequences of advance directive legal restrictions may prevent all patients, and particularly vulnerable patients, from making and communicating their end-of-life wishes and having them honored. These restrictions have rendered advance directives less clinically useful. Recommendations include improving readability, allowing oral advance directives, and eliminating witness or notary requirements. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs and the Pfizer Foundation.

Development of an LC-MS/MS Method for Non-Invasive Biomonitoring of Neonicotinoid and Systemic Herbicide Pesticide Residues in Bat Hair.

With over a quarter of the world's bats species facing extinction, there is a need for ecotoxicological studies to assess if acute and sublethal exposure to newer pesticides such as neonicotinoids and carbonates contribute to population declines. Pesticide exposure studies in bats have been limited to terminal sampling methods, therefore we developed a non-invasive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method utilizing hair trimmings. The hair of big brown bats (Eptesicus fuscus) was collected and pooled by county to assess the best extraction solvent and solid-phase-extraction (SPE) clean-up cartridges. Using the best performing extraction solvent, methanol, and the best performing SPE cartridge, Chromabond HR-X, we developed an optimized multiple reaction monitoring (MRM) LC-MS/MS method for simultaneous determination of 3 neonicotinoids, clothianidin, imidacloprid, and thiamethoxam; 1 carbonate, carbaryl; and 4 systemic herbicides, 2,4-D, atrazine, dicamba, and glyphosate. The optimized protocol yielded the detection of 3-8 of the compounds in the county-level bat hair pools. 2,4-D, glyphosate, and imidacloprid were found in all samples with two of the county-level hair samples having glyphosate concentrations of over 3500 pg/mg of hair. This approach has great potential to facilitate non-terminal ecotoxicological studies assessing the effects of subacute (chronic) pesticide exposure in threatened and endangered bat species and other species experiencing population declines.

Use of Telephone- and Internet-Based Support to Elicit and Address Financial Abuse and Mismanagement in Dementia: Experiences from the Care Ecosystem Study.

BACKGROUND: Financial mismanagement and abuse in dementia have serious consequences for patients and their families. Vulnerability to these outcomes reflects both patient and contextual factors. OBJECTIVE: Our study aimed to assess how multidisciplinary care coordination programs assist families in addressing psychosocial vulnerabilities and accessing needed resources. METHODS: Our study was embedded in a clinical trial of the Care Ecosystem, a telephone- and internet-based supportive care intervention for patients with dementia and caregivers. This program is built around the role of the Care Team Navigator (CTN), an unlicensed dementia care guide who serves as the patient and caregiver's primary point of contact, screening for common problems and providing support. We conducted a qualitative analysis of case summaries from a subset of 19 patient/caregiver dyads identified as having increased risk for financial mismanagement and abuse, to examine how Care Ecosystem staff identified vulnerabilities and provided support to patients and families. RESULTS: CTNs elicited patient and caregiver needs using templated conversations to address common financial and legal planning issues in dementia. Sources of financial vulnerability included changes in patients' behavior, caregiver burden, intrafamily tension, and confusion about resources to facilitate end-of-life planning. The Care Ecosystem staff's rapport with their dyads helped them address these issues by providing emotional support, information on how to access financial, medical, and legal resources, and improving intra-familial communication. CONCLUSION: The Care Ecosystem offers a scalable way to address vulnerabilities to financial mismanagement and abuse in patients and caregivers through coordinated care by unlicensed care guides supported by a multidisciplinary team.

In vivo stoichiometry of shelterin components.

Human telomeres bind shelterin, the six-subunit protein complex that protects chromosome ends from the DNA damage response and regulates telomere length maintenance by telomerase. We used quantitative immunoblotting to determine the abundance and stoichiometry of the shelterin proteins in the chromatin-bound protein fraction of human cells. The abundance of shelterin components was similar in primary and transformed cells and was not correlated with telomere length. The duplex telomeric DNA binding factors in shelterin, TRF1 and TRF2, were sufficiently abundant to cover all telomeric DNA in cells with short telomeres. The TPP1.POT1 heterodimer was present 50-100 copies/telomere, which is in excess of its single-stranded telomeric DNA binding sites, indicating that some of the TPP1.POT1 in shelterin is not associated with the single-stranded telomeric DNA. TRF2 and Rap1 were present at 1:1 stoichiometry as were TPP1 and POT1. The abundance of TIN2 was sufficient to allow each TRF1 and TRF2 to bind to TIN2. Remarkably, TPP1 and POT1 were approximately 10-fold less abundant than their TIN2 partner in shelterin, raising the question of what limits the accumulation of TPP1 x POT1 at telomeres. Finally, we report that a 10-fold reduction in TRF2 affects the regulation of telomere length but not the protection of telomeres in tumor cell lines.

Goals of Care Conversations and Subsequent Advance Care Planning Outcomes for People with Dementia.

BACKGROUND: Advance care planning has been shown to improve end of life decision-making for people with dementia. However, the impact of goals of care conversations between people with dementia and their caregivers has not been characterized. OBJECTIVE: In this study, we evaluate the association between goals of care conversations and advance care planning outcomes. METHODS: Retrospective advance care planning measures were collected via a questionnaire administered to 166 caregivers after the death of the person with dementia for whom they provided care. RESULTS: At time of death, the majority of decedents with dementia had advance directives, health care agents, and previous goals of care conversations with their caregiver. Goals of care conversations were significantly associated with the perceived usefulness of advance directives, the perceived adherence to advance directives, and decedent dying at their desired place of death, but not with disagreements around end-of-life care. CONCLUSION: Our findings suggest that goals of care conversations are an important component of advance care planning. These findings support the development of interventions that facilitate such conversations between people with dementia and their caregivers.

Impact of Upstream Medical Image Processing on Downstream Performance of a Head CT Triage Neural Network.

PURPOSE: To develop a convolutional neural network (CNN) to triage head CT (HCT) studies and investigate the effect of upstream medical image processing on the CNN's performance. MATERIALS AND METHODS: A total of 9776 HCT studies were retrospectively collected from 2001 through 2014, and a CNN was trained to triage them as normal or abnormal. CNN performance was evaluated on a held-out test set, assessing triage performance and sensitivity to 20 disorders to assess differential model performance, with 7856 CT studies in the training set, 936 in the validation set, and 984 in the test set. This CNN was used to understand how the upstream imaging chain affects CNN performance by evaluating performance after altering three variables: image acquisition by reducing the number of x-ray projections, image reconstruction by inputting sinogram data into the CNN, and image preprocessing. To evaluate performance, the DeLong test was used to assess differences in the area under the receiver operating characteristic curve (AUROC), and the McNemar test was used to compare sensitivities. RESULTS: The CNN achieved a mean AUROC of 0.84 (95% CI: 0.83, 0.84) in discriminating normal and abnormal HCT studies. The number of x-ray projections could be reduced by 16 times and the raw sensor data could be input into the CNN with no statistically significant difference in classification performance. Additionally, CT windowing consistently improved CNN performance, increasing the mean triage AUROC by 0.07 points. CONCLUSION: A CNN was developed to triage HCT studies, which may help streamline image evaluation, and the means by which upstream image acquisition, reconstruction, and preprocessing affect downstream CNN performance was investigated, bringing focus to this important part of the imaging chain.Keywords Head CT, Automated Triage, Deep Learning, Sinogram, DatasetSupplemental material is available for this article.© RSNA, 2021.

Multiparametric Photoacoustic Analysis of Human Thyroid Cancers In Vivo.

Thyroid cancer is one of the most common cancers, with a global increase in incidence rate for both genders. Ultrasound-guided fine-needle aspiration is the current gold standard to diagnose thyroid cancers, but the results are inaccurate, leading to repeated biopsies and unnecessary surgeries. To reduce the number of unnecessary biopsies, we explored the use of multiparametric photoacoustic (PA) analysis in combination with the American Thyroid Association (ATA) Guideline (ATAP). In this study, we performed in vivo multispectral PA imaging on thyroid nodules from 52 patients, comprising 23 papillary thyroid cancer (PTC) and 29 benign cases. From the multispectral PA data, we calculated hemoglobin oxygen saturation level in the nodule area, then classified the PTC and benign nodules with multiparametric analysis. Statistical analyses showed that this multiparametric analysis of multispectral PA responses could classify PTC nodules. Combining the photoacoustically indicated probability of PTC and the ATAP led to a new scoring method that achieved a sensitivity of 83% and a specificity of 93%. This study is the first multiparametric analysis of multispectral PA data of thyroid nodules with statistical significance. As a proof of concept, the results show that the proposed new ATAP scoring can help physicians examine thyroid nodules for fine-needle aspiration biopsy, thus reducing unnecessary biopsies. SIGNIFICANCE: This report highlights a novel photoacoustic scoring method for risk stratification of thyroid nodules, where malignancy of the nodules can be diagnosed with 83% sensitivity and 93% specificity.

Improving Medical-Legal Advance Care Planning.

The importance of advance care planning (ACP) has been increasingly recognized by health systems. However, 46%-76% of patients report engaging in ACP with lawyers, whereas only a minority report doing so with physicians. In the U.S., ACP with lawyers focuses on advance directive documents, naturally occurs outside of health care contexts, and is often uninformed by the clinical context, such as one's prognosis and clinical trajectory. These forms are regularly stored at home or at a lawyer's office and not available at the bedside when needed in a medical crisis. Yet, in contrast to clinicians, lawyers hold sophisticated knowledge about their states' advance directive law. Lawyers may also understand clients' socioeconomic context and plans more broadly, which are known to be critical for contextualizing and personalizing patient care but are often not well captured in health care. Aligning medical and legal approaches to ACP is important to ensuring the quality and value of those efforts. As an important first step toward this goal, we convened an interprofessional panel of medical and legal experts to elucidate the state of medical-legal ACP and begin to identify strategies to improve and align practices within and across professions. This article describes the historical disconnects between the medical and legal practice of ACP, recommendations and products of the interprofessional panel, and recommendations for future medical-legal collaboration.

COUNTCOLORS, AN R PACKAGE FOR QUANTIFICATION OF THE FLUORESCENCE EMITTED BY PSEUDOGYMNOASCUS DESTRUCTANS LESIONS ON THE WING MEMBRANES OF HIBERNATING BATS.

Pseudogymnoascus destructans colonizes the wing membrane of hibernating bats with the potential to form dense fungal hyphae aggregates within cupping erosions. These fungal cupping erosions emit a characteristic fluorescent orange-yellow color when the wing membrane is transilluminated with 385 nm ultraviolet (UV) light. The purpose of this study was to create and validate the R package, countcolors, for quantifying the distinct orange-yellow UV fluorescence in bat-wing membrane lesions caused by P. destructans. Validation of countcolors was completed by first quantifying the percent area of 20, 2.5 cm2 images. These generated images were of two known pixel colors ranging from 0% to 100% of the pixels. The countcolors package accurately measured the known proportion of a given color in each image. Next, 40, 2.5 cm2 sections of UV transilluminated photographs of little brown bat (Myotis lucifugus) wings were given to a single evaluator. The area of fluorescence was both manually measured and calculated using image analysis software and quantified with countcolors. There was good agreement between the two methods (Pearson's correlation=0.915); however, the manual use of imaging software showed a consistent negative bias. Reproducibility of the analysis methods was tested by providing the same images to naive evaluators who previously never used the software; no significant difference (P=0.099) was found among evaluators. Using the R package countcolors takes less time than does manually measuring the fluorescence in image analysis software, and our results showed that countcolors can improve the accuracy when quantifying the area of P. destructans infection in bat wing-membranes.