Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing advanced adenomatous polyps in Black patients.

BACKGROUND: Chemoprevention of colorectal neoplasia with aspirin and statins is under-investigated in Black patients. Since Black patients suffer disproportionately from colon cancer incidence and mortality compared to other populations, we investigated the utility of aspirin and statin in reducing advanced adenomatous polyp (AAP) risk in Black patients. METHODS: We carried out a retrospective cohort study of screening colonoscopies performed at a large urban academic center from 1/1/2011 through 12/31/2019. We analyzed self-identified Black patients with > 1 colonoscopy and no personal history of either inflammatory bowel disease or colon cancer syndromes. Our primary endpoint was first AAP development after index colonoscopy among Black patients taking both aspirin and a statin compared to those taking one or neither medication. We used multivariate logistic regression modeling to investigate our outcomes. RESULTS: We found data on chemoprophylaxis use in 560 patients. The mean observation period between index colonoscopy and AAP identification was 4 years. AAP developed in 106/560 (19%) of our cohort. We found no difference in AAP risk among Black patients taking both chemoprevention medications compared to partial or no chemoprophylaxis (20% vs 18% respectively, p = 0.49). This finding remained after adjusting for age, body mass index, and tobacco use (odds ratio 1.04, 95% CI 0.65-1.67; p = 0.87). CONCLUSIONS: Short-term aspirin-statin chemoprevention did not reduce the risk of AAP development in our cohort of Black patients. Larger and long-term prospective investigations are needed to investigate the utility of chemoprophylaxis in this population. TRIAL REGISTRATION: Not applicable.

Schema learning for the cocktail party problem.

The cocktail party problem requires listeners to infer individual sound sources from mixtures of sound. The problem can be solved only by leveraging regularities in natural sound sources, but little is known about how such regularities are internalized. We explored whether listeners learn source "schemas"-the abstract structure shared by different occurrences of the same type of sound source-and use them to infer sources from mixtures. We measured the ability of listeners to segregate mixtures of time-varying sources. In each experiment a subset of trials contained schema-based sources generated from a common template by transformations (transposition and time dilation) that introduced acoustic variation but preserved abstract structure. Across several tasks and classes of sound sources, schema-based sources consistently aided source separation, in some cases producing rapid improvements in performance over the first few exposures to a schema. Learning persisted across blocks that did not contain the learned schema, and listeners were able to learn and use multiple schemas simultaneously. No learning was evident when schema were presented in the task-irrelevant (i.e., distractor) source. However, learning from task-relevant stimuli showed signs of being implicit, in that listeners were no more likely to report that sources recurred in experiments containing schema-based sources than in control experiments containing no schema-based sources. The results implicate a mechanism for rapidly internalizing abstract sound structure, facilitating accurate perceptual organization of sound sources that recur in the environment.

Political transition and emergent forest-conservation issues in Myanmar.

Political and economic transitions have had substantial impacts on forest conservation. Where transitions are underway or anticipated, historical precedent and methods for systematically assessing future trends should be used to anticipate likely threats to forest conservation and design appropriate and prescient policy measures to counteract them. Myanmar is transitioning from an authoritarian, centralized state with a highly regulated economy to a more decentralized and economically liberal democracy and is working to end a long-running civil war. With these transitions in mind, we used a horizon-scanning approach to assess the 40 emerging issues most affecting Myanmar's forests, including internal conflict, land-tenure insecurity, large-scale agricultural development, demise of state timber enterprises, shortfalls in government revenue and capacity, and opening of new deforestation frontiers with new roads, mines, and hydroelectric dams. Averting these threats will require, for example, overhauling governance models, building capacity, improving infrastructure- and energy-project planning, and reforming land-tenure and environmental-protection laws. Although challenges to conservation in Myanmar are daunting, the political transition offers an opportunity for conservationists and researchers to help shape a future that enhances Myanmar's social, economic, and environmental potential while learning and applying lessons from other countries. Our approach and results are relevant to other countries undergoing similar transitions.

Establishing Theoretical Stability and Treatment Integrity for Motivational Interviewing.

BACKGROUND: There is increasing evidence claiming the effectiveness of motivational interviewing (MI) in promoting behavioural change. However, ongoing changes to MI theory and practice have implications for its transferability, accessibility and for the validity of previous findings. Lack of practice consistency may make its effectiveness difficult to evaluate. AIMS: This paper explores the complexity of MI and issues in the development of evidence-based practice in delivery, before describing issues related to practitioner application. METHOD: Theoretical and practice developments over the last 30 years are reviewed under the headings theory, practice and efficacy. Specifically, developments across the three editions of the core MI texts are examined. RESULTS: Findings from the literature suggest a lack of theoretical stability and practice integrity, with recent fundamental changes to the underpinning structure of MI. Issues relating to the transferability and acquisition of MI skills, consistency of delivery and mechanisms underlying change are discussed. CONCLUSIONS: The authors call for greater theoretical stability, more transparency over how developments are based on theoretical principles and empirical outcomes, and clearer guidance about how this informs practice development and delivery of MI.

Treatment allocation in patients with early-stage esophageal adenocarcinoma: Prevalence and predictors of lymph node involvement.

BACKGROUND: In considering treatment allocation for patients with early esophageal adenocarcinoma, the incidence of lymph node metastasis is a critical determinant; however, this has not been well defined or stratified by the relevant clinical predictors of lymph node spread. METHODS: Data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute were abstracted from 2004 to 2010 for patients with early-stage esophageal adenocarcinoma. The incidence of lymph node involvement for patients with Tis, T1a, and T1b tumors was examined and was stratified by predictors of spread. RESULTS: A total of 13,996 patients with esophageal adenocarcinoma were evaluated. Excluding those with advanced, metastatic, and/or invasive (T2-T4) disease, 715 patients with Tis, T1a, and T1b tumors were included. On multivariate analysis, tumor grade (odds ratio [OR], 2.76; 95% confidence interval [95% CI], 1.58-4.82 [P<.001]), T classification (OR, 0.47; 95% CI, 0.24-0.91 [P =.025]), and tumor size (OR, 2.68; 95% CI, 1.48-4.85 [P = .001]) were found to be independently associated with lymph node metastases. There was no lymph node spread noted with Tis tumors. For patients with low-grade (well or moderately differentiated) tumors measuring <2 cm in size, the risk of lymph node metastasis was 1.7% for T1a (P<.001) and 8.6% for T1b (P = .001) tumors. CONCLUSIONS: For patients with low-grade Tis or T1 tumors measuring ≤2 cm in size, the incidence of lymph node metastasis appears to be comparable to the mortality rate associated with esophagectomy. For highly selected patients with early esophageal adenocarcinomas, the results of the current study support the recommendation that local endoscopic resection can be considered as an alternative to surgical management when followed by rigorous endoscopic and radiographic surveillance. Cancer 2016;122:2150-7. © 2016 American Cancer Society.

The effect of limb dominance on lower limb functional performance--a systematic review.

Lower limb dominance (or lateral preference) could potentially effect functional performance. Clinicians are often asked to make judgements as to when a patient has sufficiently "recovered" from an injury, typically using strength and dynamic performance outcome measures. The primary purpose of this study was to systematically review the literature in relation to limb dominance within active adult populations and discuss some limitations to current methods and relate this to current clinical practice. A search of MEDLINE and CINAHL and EMBASE databases and reference lists of those articles identified was performed. Eleven articles were selected for meta-analysis. There was no statistical effect of limb dominance for any of the functional tests: isokinetic quadriceps and hamstring tests, hamstring:quadriceps ratios, single-leg hop for distance, single-leg vertical jump and vertical ground reaction force following a single-leg vertical jump. Pooled symmetry values varied from 94.6% to 99.6% across the tests, above the clinically accepted benchmark of 90% used in clinical practice. Although the results of this study must be used with discretion, asymmetries in the tasks described in this analysis should be viewed as undesirable and remedied accordingly. Further research is needed to quantify asymmetries, particularly in relation to sport-specific contexts.

In vivo endomicroscopy improves detection of Barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video).

BACKGROUND: Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barrett's esophagus (BE). OBJECTIVE: To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. DESIGN: Multicenter, randomized, controlled trial. SETTING: Academic medical centers. PATIENTS: Adult patients with BE undergoing routine surveillance or referred for early neoplasia. INTERVENTION: Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. MAIN OUTCOME MEASUREMENTS: Diagnostic yield, performance characteristics, clinical impact. RESULTS: A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. LIMITATIONS: Tertiary-care referral centers and expert endoscopists limit generalizability. CONCLUSION: Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01124214.).

Rapid modulation in music supports attention in listeners with attentional difficulties.

Background music is widely used to sustain attention, but little is known about what musical properties aid attention. This may be due to inter-individual variability in neural responses to music. Here we find that music with amplitude modulations added at specific rates can sustain attention differentially for those with varying levels of attentional difficulty. We first tested the hypothesis that music with strong amplitude modulation would improve sustained attention, and found it did so when it occurred early in the experiment. Rapid modulations in music elicited greater activity in attentional networks in fMRI, as well as greater stimulus-brain coupling in EEG. Finally, to test the idea that specific modulation properties would differentially affect listeners based on their level of attentional difficulty, we parametrically manipulated the depth and rate of amplitude modulations inserted in otherwise-identical music, and found that beta-range modulations helped more than other modulation ranges for participants with more ADHD symptoms. Results suggest the possibility of an oscillation-based neural mechanism for targeted music to support improved cognitive performance.

Targeting the glutamine metabolism to suppress cell proliferation in mesenchymal docetaxel-resistant prostate cancer.

Docetaxel (DX) serves as a palliative treatment option for metastatic prostate cancer (PCa). Despite initial remission, acquired DX resistance is inevitable. The mechanisms behind DX resistance have not yet been deciphered, but a mesenchymal phenotype is associated with DX resistance. Mesenchymal phenotypes have been linked to metabolic rewiring, obtaining most ATP production by oxidative phosphorylation (OXPHOS) powered substantially by glutamine (Gln). Likewise, Gln is known to play an essential role in modulating bioenergetic, redox homeostasis and autophagy. Herein, investigations of Gln deprivation on DX-sensitive and -resistant (DR) PCa cells revealed that the DR cell sub-lines were susceptible to Gln deprivation. Mechanistically, Gln deprivation reduced OXPHOS and ATP levels, causing a disturbance in cell cycle progression. Genetic and chemical inhibition of the Gln-metabolism key protein GLS1 could validate the Gln deprivation results, thereby representing a valid therapeutic target. Moreover, immunohistological investigation of GLS1 revealed a high-expressing GLS1 subgroup post-docetaxel failure, exhibiting low overall survival. This subgroup presents an intriguing opportunity for targeted therapy focusing on glutamine metabolism. Thus, these findings highlight a possible clinical rationale for the chemical inhibition of GLS1 as a therapeutic strategy to target mesenchymal DR PCa cells, thereby delaying accelerated tumour progression.

Clonal hematopoiesis and its impact on the aging osteo-hematopoietic niche.

Clonal hematopoiesis (CH) defines a premalignant state predominantly found in older persons that increases the risk of developing hematologic malignancies and age-related inflammatory diseases. However, the risk for malignant transformation or non-malignant disorders is variable and difficult to predict, and defining the clinical relevance of specific candidate driver mutations in individual carriers has proved to be challenging. In addition to the cell-intrinsic mechanisms, mutant cells rely on and alter cell-extrinsic factors from the bone marrow (BM) niche, which complicates the prediction of a mutant cell's fate in a shifting pre-malignant microenvironment. Therefore, identifying the insidious and potentially broad impact of driver mutations on supportive niches and immune function in CH aims to understand the subtle differences that enable driver mutations to yield different clinical outcomes. Here, we review the changes in the aging BM niche and the emerging evidence supporting the concept that CH can progressively alter components of the local BM microenvironment. These alterations may have profound implications for the functionality of the osteo-hematopoietic niche and overall bone health, consequently fostering a conducive environment for the continued development and progression of CH. We also provide an overview of the latest technology developments to study the spatiotemporal dependencies in the CH BM niche, ideally in the context of longitudinal studies following CH over time. Finally, we discuss aspects of CH carrier management in clinical practice, based on work from our group and others.

Impact of atherosclerosis imaging-quantitative computed tomography on diagnostic certainty, downstream testing, coronary revascularization, and medical therapy: the CERTAIN study.

AIMS: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. METHODS AND RESULTS: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. CONCLUSION: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy.

Practitioner Review: The effectiveness of solution focused brief therapy with children and families: a systematic and critical evaluation of the literature from 1990-2010.

BACKGROUND AND SCOPE: Solution focused brief therapy (SFBT) is a strengths-based therapeutic approach, emphasizing the resources that people possess and how these can be applied to a positive change process. The current study provides a systematic review of the SFBT evidence base and a critical evaluation of the use and application of SFBT in clinical practice with children and families. METHODS: Between 21 December 2010 and 12 May 2011 forty-four database searches (including, PsychInfo, ISI Web of Knowledge, ASSIA, British Education Index, Medline and Scopus), web searches and consultation with experts in the field were used to identify reports of SFBT studies published between 1990 and 2010. Studies were then screened according to trialled qualitative and quantitative assessment frameworks and reported according to the PRISMA guidelines. RESULTS: A total of 38 studies were included in the review. Of these, 9 applied SFBT to internalizing child behaviour problems, 3 applied SFBT to both internalizing and externalizing child behaviour problems, 15 applied the approach to externalizing child behaviour problems and 9 evaluated the application of SFBT in relation to a range of other issues. CONCLUSIONS: Although much of the literature has methodological weaknesses, existing research does provide tentative support for the use of SFBT, particularly in relation to internalizing and externalizing child behaviour problems. SFBT appears particularly effective as an early intervention when presenting problems are not severe. Further well-controlled outcome studies are needed. Studies included in the review highlight promising avenues for further research.

Interobserver agreement for the detection of Barrett's esophagus with optical frequency domain imaging.

BACKGROUND: Optical frequency domain imaging (OFDI) is a second-generation form of optical coherence tomography (OCT) providing comprehensive cross-sectional views of the distal esophagus at a resolution of ~7 µm. AIM: Using validated OCT criteria for squamous mucosa, gastric cardia mucosa, and Barrett's esophagus (BE), the objective of this study was to determine the inter- and intra-observer agreements by a large number of OFDI readers for differentiating these tissues. METHODS: OFDI images were obtained from nine subjects undergoing screening and surveillance for BE. Sixty-four OFDI image regions of interest were randomly selected for review. A training set of 19 images was compiled distinguishing squamous mucosa from gastric cardia and BE using previously validated OCT criteria. The ten readers then interpreted images in a test set of 45 different images of squamous mucosa (n = 15), gastric cardia (n = 15), or BE (n = 15). Interobserver agreement differentiating the three tissue types and BE versus non-BE mucosa was determined using multi-rater Fleiss's κ value. The images were later randomized again and four readers repeated the test 3 weeks later to assess intraobserver reliability. RESULTS: All ten readers showed excellent agreement for the differentiation of BE versus non-BE mucosa (κ = 0.811 p < 0.0001) and for differentiating BE versus gastric cardia versus squamous mucosa (κ = 0.866, p < 0.0001). For the four readers who repeated the test, the median intraobserver agreement (BE vs. non-BE) was high (κ = 0.975, IQR: 0.94, 1.0). CONCLUSIONS: Trained readers have a high interobserver agreement for differentiating BE, squamous, and gastric cardia mucosa using OFDI.

Transanal rectosigmoid resection via natural orifice translumenal endoscopic surgery (NOTES) with total mesorectal excision in a large human cadaver series.

BACKGROUND: The authors' group has previously described successful transanal rectosigmoid resection via natural orifice translumenal endoscopic surgery (NOTES) in both porcine and cadaveric models using the transanal endoscopic microsurgery platform. This report describes the largest cadaveric series to date as optimization of this approach for clinical application continues. METHODS: Between December 2008 and September 2011, NOTES transanal rectosigmoid resection with total mesorectal excision (TME) was successfully performed in 32 fresh human cadavers using transanal dissection alone (n = 19), with transgastric endoscopic assistance (n = 5), or with laparoscopic assistance (n = 8). The variables recorded were gender, body mass index (BMI), operative time, length of the mobilized specimen, integrity of the mesorectum and the resected specimen, and complications. Univariate statistical analysis was performed. RESULTS: Of the 32 cadavers, 22 were male with a mean BMI of 24 kg/m(2) (range 16.3-37 kg/m(2)). The mean operative time was 5.1 h (range 3-8 h), and the mean specimen length was 53 cm (range 15-91.5 cm). After the first five cadavers, specimen length significantly improved, and a trend toward decreased operative time was demonstrated. The mesorectum was intact in 100% of the specimens. In nine cadavers, endoscopic dissection was complicated by organ injury. Evaluation by the operative approach demonstrated a significantly longer specimen with laparoscopic assistance (67.7 cm) than with transgastric assistance (45.4 cm) or transanal dissection alone (49.2 cm) (p = 0.013). Comparison of the technique used for inferior mesenteric pedicle division demonstrated both significantly decreased operative time (4.8 vs 6 h; p = 0.024) and increased specimen length (57.7 vs 39.6 cm; p = 0.025) when a stapler was used in lieu of a bipolar cautery device. CONCLUSION: Transanal NOTES rectosigmoid resection with TME is feasible and demonstrates improvement in specimen length and operative time with experience. Transitioning to clinical application requires laparoscopic assistance to overcome limitations related to NOTES instrumentation, as well as procedural training with fresh human cadavers.

Electrical alternans: a sign, not a diagnosis.

Electrical alternans is an electrocardiographic phenomenon defined as an alternating amplitude or axis of the QRS complexes in any or all leads. It is most commonly associated with a large pericardial effusion and impending threat of cardiac tamponade; however, a literature review showed that this electrocardiographic finding can be seen in a variety of other clinical scenarios with varying etiologies and prognoses. Several electrocardiogram examples are presented with a brief review of the potential mechanisms and clinical significance and demonstrate that electrical alternans is more correctly considered an electrocardiographic sign, rather than a diagnosis, with a broad differential for potential etiologies. For some causes, the clinical significance is well known, but for others, further research is needed.

The prognostic significance of coronary CT angiography.

Coronary computed tomography angiography (CTA) is an increasingly utilized, highly accurate noninvasive test for the diagnosis of coronary artery disease. Accumulating data have convincingly demonstrated that the presence, extent, and location of both obstructive and nonobstructive coronary atherosclerosis visualized on coronary CTA conveys powerful prognostic information, incremental to that provided by clinical variables and coronary calcium scoring. Proposed markers of future plaque instability and coronary risk, such as the degree of vessel remodeling and low-attenuation plaque volume, as well as measures of CT myocardial perfusion, may further improve the prognostic value of CTA. Ultimately, studies are needed to assess whether the prognostic information provided by coronary CTA testing results in sustained changes in patient and provider behaviors that cost effectively improve patient outcomes.

Cardiac safety and clinical efficacy of high-dose domperidone for long-term treatment of gastroparesis symptoms.

Domperidone is an effective antiemetic used worldwide, but there have been reports of possible cardiotoxicity. Our goal was to explore the cardiac safety and clinical efficacy of long-term domperidone, titrated as high as 120 mg/day, in patients not responding or unable to tolerate other therapies for gastroparesis (GP).This retrospective cohort study was conducted at a single tertiary care academic center. We objectively assessed the safety and efficacy of domperidone through questionnaires, clinical follow-up and frequent ECGs as mandated by the Food and Drug Administration. We excluded patients with a history of dangerous arrhythmias, prolonged QTc, clinically significant electrolyte disturbances, gastrointestinal hemorrhage or obstruction, presence of a prolactinoma, pregnant or breastfeeding females, or allergy to domperidone. A total of 21 patients met the inclusion criteria for eligibility in this study (52.4% white, 42.9% Hispanic; mean age 50.1 years; 90.5% female). The mean duration of domperidone therapy was 52.3 (range 16-97) months with a mean highest dose of 80 mg/day (range 40-120 mg). Two patients (9.5%) taking 120 mg/day experienced asymptomatic meaningful QTc prolongation (>450 ms in males, >470 ms in females). One-third of patients had asymptomatic non-meaningful QTc prolongation. Palpitations or chest pain was reported in 19% of patients without ECG abnormalities or adverse cardiac events. The mean severity of vomiting and nausea was improved by 82% and 55%, respectively.Long-term treatment with high doses of domperidone (40-120 mg/day) improved GP symptoms in patients previously refractory to other medical therapies and with a satisfactory cardiovascular risk profile.

Dithranol as novel co-adjuvant for non-invasive dermal vaccination.

Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8+ T cells and CD4+ T cells with a TH1 cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans.

First interobserver agreement of optical coherence tomography in the bile duct: A multicenter collaborative study.

Background and study aims Optical coherence tomography (OCT) is a new technology available for evaluation of indeterminate biliary strictures. It allows under-the-surface visualization and preliminary studies have confirmed standardized characteristics associated with malignancy. The aim of this study is to evaluate the first interobserver agreement in identifying previously agreed upon OCT criteria and diagnosing of malignant versus benign disease. Patients and methods Fourteen endoscopists were asked to review an atlas of reference clips and images of eight criteria derived from expert consensus A total of 35 de-identified video clips were then evaluated for presence of the eight criteria and for final diagnosis of malignant versus benign using the atlas as reference Intraclass correlation (ICC) analysis was done to evaluate interrater agreement. Results Clips of 23 malignant lesions and 12 benign lesions were scored. Excellent interobserver agreement was seen with dilated hypo-reflective structures (0.85) and layering effacement (0.89); hyper-glandular mucosa (0.76), intact layering (0.81), and onion-skin layering (0.77); fair agreement was seen with scalloping (0.58), and thickened epithelium (0.4); poor agreement was seen with hyper-reflective surface (0.36). The diagnostic ICC for both neoplastic (0.8) and non-neoplastic (0.8) was excellent interobserver agreement. The overall diagnostic accuracy was 51 %, ranging from 43 % to 60 %. Conclusions Biliary OCT is a promising new modality for evaluation of indeterminate biliary strictures. Interobserver agreement ranged from fair to almost perfect on eight previously identified criteria. Interobserver agreement for malignancy diagnosis was substantial (0.8). Further studies are needed to validate this data.

Dynamic Changes of the Bone Marrow Niche: Mesenchymal Stromal Cells and Their Progeny During Aging and Leukemia.

Mesenchymal stromal cells (MSCs) are a heterogenous cell population found in a wide range of tissues in the body, known for their nutrient-producing and immunomodulatory functions. In the bone marrow (BM), these MSCs are critical for the regulation of hematopoietic stem cells (HSC) that are responsible for daily blood production and functional immunity throughout an entire organism's lifespan. Alongside other stromal cells, MSCs form a specialized microenvironment BM tissue called "niche" that tightly controls HSC self-renewal and differentiation. In addition, MSCs are crucial players in maintaining bone integrity and supply of hormonal nutrients due to their capacity to differentiate into osteoblasts and adipocytes which also contribute to cellular composition of the BM niche. However, MSCs are known to encompass a large heterogenous cell population that remains elusive and poorly defined. In this review, we focus on deciphering the BM-MSC biology through recent advances in single-cell identification of hierarchical subsets with distinct functionalities and transcriptional profiles. We also discuss the contribution of MSCs and their osteo-adipo progeny in modulating the complex direct cell-to-cell or indirect soluble factors-mediated interactions of the BM HSC niche during homeostasis, aging and myeloid malignancies. Lastly, we examine the therapeutic potential of MSCs for rejuvenation and anti-tumor remedy in clinical settings.