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Background and Aim: Barrett's oesophagus predisposes individuals to oesophageal adenocarcinoma (OAC), with the risk of progression to malignancy increasing with the degree of dysplasia, categorized as either low‐grade dysplasia (LGD) or high‐grade dysplasia (HGD). The reported incidence of progression to OAC in LGD ranges from 0.02% to 11.43% per annum. In patients with LGD, Australian guidelines recommend 6‐monthly endoscopic surveillance. We aimed to describe the surveillance practices within a tertiary centre, and to determine the predictive value of surveillance as well as other risk factors for progression. Methods: Endoscopy and pathology databases were searched over a 10‐year period to collate all cases of Barrett's oesophagus with LGD. Medical records were reviewed to document patient factors and endoscopic and histologic details. Because follow‐up times varied greatly, survival analysis techniques were employed. Results: Fifty‐nine patients were found to have LGD. Thirteen patients (22.0%) progressed to either HGD or OAC (10 (16.9%) and three (5.1%) respectively); the annual incidence rates of progression to HGD/OAC and OAC were 5.5% and 1.1% respectively. All patients who developed OAC had non‐guideline‐adherent surveillance. A Cox model found only two predictors of progression: (i) guideline‐adherent surveillance, performed in 16 (27.1%), detected progression to HGD/OAC four times earlier than non‐guideline‐adherent surveillance (95% confidence interval (CI) = 1.3–12.3; P = 0.016). (ii) The detection of visible lesions at exit endoscopy independently predicted progression (hazard ratio = 6.5; 95% CI = 1.9–22.8; P = 0.003). Conclusion: Barrett's oesophagus with LGD poses a significant risk of progression to HGD/OAC. Guideline‐recommended surveillance is effective, but is difficult to adhere to. Clinical predictors for those who are more likely to progress are yet to be defined. [ABSTRACT FROM AUTHOR]

Glycine Transporter 2 (GlyT2) inhibitors have shown considerable potential as analgesics for the treatment of neuropathic pain but also display considerable side effects. One potential source of side effects is irreversible inhibition. In this study, we have characterized the mechanism of ORG25543 inhibition of GlyT2 by first considering three potential ligand binding sites on GlyT2—the substrate site, the vestibule allosteric site and the lipid allosteric site. The three sites were tested using a combination of molecular dynamics simulations and analysis of the inhibition of glycine transport of a series point mutated GlyT2 using electrophysiological methods. We demonstrate that the lipid allosteric site on GlyT2 is the most likely binding site for ORG25543. We also demonstrate that cholesterol derived from the cell membrane can form specific interactions with inhibitor‐bound transporters to form an allosteric network of regulatory sites. These observations will guide the future design of GlyT2 inhibitors with the objective of minimising on‐target side effects and improving the therapeutic window for the treatment of patients suffering from neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness. Objectives: To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness. Study design: Longitudinal. Methods: Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC–MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated by body‐mounted inertial sensor (BMIS) and 10‐point subjective lameness score on day 21 and compared to untreated baseline evaluation on day 35. Clinicopathological analysis (n = 12), hepatic biopsy (n = 6) and gastroscopy (n = 6) were evaluated on days −1 and 22. Results: Maximum plasma acetaminophen concentration (Cmax) was 20.83 ± 10.25 μg/mL at time (Tmax) 0.40 ± 0.22 h on day 7. The Cmax on day 21 was 17.33 ± 6.91 μg/mL with a Tmax of 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post‐treatment; Significant percent improvement was detected in PDmax for horses with hindlimb lameness at 1, 2 and 8 h post‐treatment. There were no significant differences in gastroscopy or hepatic biopsy scores between days −1 and 22. Main limitations: Small sample size, multi‐limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation. Conclusions: In horses with naturally occurring chronic lameness, acetaminophen at 30 mg/kg produced a transient improvement in subjective lameness and BMIS evaluation. Acetaminophen may not be effective as a monotherapy. Acetaminophen was safe following 21 days of 30 mg/kg PO every 12 h, with no evidence of clinically significant changes in clinicopathological analysis, hepatic biopsy or gastric ulceration scores. [ABSTRACT FROM AUTHOR]

Background: The application of machine learning (ML) tools in electronic health records (EHRs) can help reduce the underdiagnosis of dementia, but models that are not designed to reflect minority population may perpetuate that underdiagnosis. Method: To address the underdiagnosis of dementia in both Black Americans (BAs) and white Americans (WAs), we sought to develop and validate ML models that assign race‐specific risk scores. These scores were used to identify undiagnosed dementia in BA and WA Veterans in EHRs. More specifically, risk scores were generated separately for BAs (n = 10K) and WAs (n = 10K) in training samples of cases and controls by performing ML, equivalence mapping, topic modeling, and a support vector‐machine (SVM) in structured and unstructured EHR data. Scores were validated via blinded manual chart reviews (n = 1.2K) of controls from a separate sample (n = 20K). AUCs and negative and positive predictive values (NPVs and PPVs) were calculated to evaluate the models. Result: Among Veterans with undiagnosed dementia who underwent chart review, those diagnosed by expert clinician reviewers with possible/probable dementia had higher ADRD ML risk scores compared to those diagnosed with no dementia (0.45 [0.38] vs. ‐0.02 [0.51] for BAs, and 0.38 [0.41] vs. ‐0.02 [0.47] for WAs; (see figure 1). Of the 1,200 Veterans who underwent chart review, 15.3% (n = 92) of BAs and 9.5% (n = 57) of WAs were identified with possible/probable dementia. However, adjusting for oversampling of Veterans with higher scores, the adjusted estimated prevalence was 4.1% for BA Veterans and 3.6% for WA Veterans. There was a strong positive relationship between risk scores and the prevalence of undiagnosed dementia (Figure 2). As anticipated, for Veterans with scores below the 90th percentile, the percentages of undiagnosed dementia were low: 3.9% for BA and 2.9% for WA Veterans. Among Veterans with scores above the 90th percentile, we found that a higher percentage of BA Veterans had undiagnosed dementia than WA Veterans: 25.6% vs. 15.3%. Conclusion: Our findings suggest that race‐specific ML models can assist in the identification of undiagnosed dementia, particularly in BAs. Future studies should investigate implementing EHR‐based risk scores in clinics that serve both BA and WA Veterans. [ABSTRACT FROM AUTHOR]

Background: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are challenging to differentiate. Mobile health devices that measure motor and sleep domains between clinic visits may improve differential diagnosis. Method: Participants with probable AD and probable DLB wore ActiGraph triaxial wGT3X‐BT actigraphy devices on their nondominant wrists for 2 weeks and multichannel Sleep ProfilerX8TM EEG devices on their foreheads for 2 consecutive nights.3 Actigraphy data were processed and scored using GGIR and activity counts in R. The Sleep Profiler characterizes abnormal slow‐wave sleep and non‐REM hypertonia (NRH). Result: At baseline, participants with DLB (n = 9) had higher UPDRS scores and a higher likelihood of psychosis than participants with AD (n = 8; see Table 1). Using univariate Wilcoxon Rank‐Sum tests, we found that at baseline participants with DLB had lower daily activity counts, higher % time in NRH, and lower % time in REM sleep than participants with AD (unadjusted p‐values < 0.05; See Figure 1). In a recent 6‐month followup, activity levels were lower on average than baseline activity levels for both DLB (n = 5) and AD (n = 5). at 6‐months, the differences in % sleep in NRH increased between DLB participants (n = 5) and AD participants (n = 3) as average % NRH increase 6% in DLB and decreased 1% in AD (see Table 2). These 6‐month differences are not statistically significant, but data collection are ongoing. An exploration of methods for processing and scoring actigraphy data revealed that processing can result in wide range of findings. As a result, we have focused on actigraphy outcomes which are more suitable to older participants with dementia. Conclusion: Participants with DLB demonstrated lower baseline physical activity and higher rates of baseline sleep disturbances than participants with AD; sleep differences between DLB and AD appeared to increase over 6 months. Actigraphy and sleep‐monitoring devices are well tolerated in participants with dementia and they can reliably collect valid, useful activity and sleep data in between clinic visits. [ABSTRACT FROM AUTHOR]

Background: Dementia with Lewy bodies (DLB) is difficult to differentiate from Alzheimer's disease (AD) in clinical settings. Actigraphy and sleep‐monitoring devices have the potential to generate data in between clinic visits to help improve the identification of DLB. Objective: We will assess the feasibility of measuring activity and sleep, including day/night reversal, in participants with DLB (n=5) and AD (n=4). Method: Participants were asked to wear actigraphy devices on their wrists for 2 weeks and sleep‐monitoring EEG devices on their foreheads for 2 nights. Actigraphy recording errors were detected by logging instances in which the majority of acceleration values approached the maximum; reliability was evaluated by logging 15‐minute actigraphy and 1‐hour sleep‐monitoring periods with at least some valid data. Actigraphy tolerability was evaluated by examining non‐wear times. Ten variables were selected to evaluate day/night reversal. Result: Averaged across all individuals, only 0.02% of the 15‐minute actigraphy recording periods had a recording error, 100% of the 15‐minute periods had at least some valid data, and only 0.15% of the periods reflected non‐wear times. For the sleep‐monitoring device, an average of 78% of each nightly recording were considered valid. Of the ten day/night reversal variables, two sleep‐monitor variables showed the strongest differences between DLB and AD: sleep efficiency (mean [SD] = 0.56 [0.19] for DLB; mean [SD] = 0.74 [0.11] for AD; see Fig. 1) and percent sleep in REM (mean [SD] = 6.83 [9.16] for DLB; mean [SD] = 18.3 [4.13] for AD; see Fig. 2). The ratio of nighttime to daytime activity as measured by actigraphy (mean [SD] = 0.37 [0.18] for DLB; mean [SD] = 0.38 [0.08] for AD) showed strong differences in the variability of measurements between AD and DLB (see Fig. 3). Conclusion: These findings suggest that actigraphy and sleep‐monitoring devices are tolerable for participants with dementia and that the devices can reliably collect valid activity and sleep data in between clinic visits. Sleep efficiency and percentage REM sleep were lower in participants with DLB than in participants with AD. Larger studies should further explore the promise of actigraphy and sleep‐monitoring devices for differentiating DLB and AD. [ABSTRACT FROM AUTHOR]

Background: Monitoring blood glucose concentrations is common in critically ill neonatal foals, especially septic foals and those receiving naso‐esophageal feedings or IV parenteral nutrition. Glucose typically is measured using a point‐of‐care (POC) glucometer but requires repeated restraint and blood collections, which may cause irritation at venipuncture sites and increased demands on nursing staff. Continuous glucose monitoring systems (CGMS) may provide an accurate alternative for monitoring blood glucose concentration. Objectives: To determine the correlation and accuracy of a CGMS to monitor neonatal foals' blood glucose concentrations as compared to a POC glucometer and laboratory chemistry analysis (CHEM). Animals: Samples from 4 healthy and 4 ill neonatal foals. Methods: A CGMS was placed on each foal, and glucose measurements acquired from this device were compared to simultaneous measurements of blood glucose concentration using a POC glucometer and CHEM. Results: Two‐hundred matched glucose measurements were collected from 8 neonatal foals. The mean bias (95% limits of agreement) between CGMS and CHEM, CGMS and POC glucometer, and POC glucometer and CHEM was 3.97 mg/dL (−32.5 to 40.4), 18.2 mg/dL (−28.8 to 65.2), and 22.18 mg/dL (−9.3 to 53.67), respectively. The Pearson's correlation coefficient (r) was significantly correlated among all devices: GCMS and CHEM (r = 0.81), CGMS and POC glucometer (r = 0.77) and POC glucometer‐CHEM (r = 0.92). Conclusions and Clinical Importance: Within the blood glucose concentration ranges in this study (78‐212 mg/dL), CGMS measurements were significantly correlated with CHEM, suggesting that it is an acceptable method to provide meaningful, immediate, and continuous glucose concentration measurements in neonatal foals while eliminating the need for repeated restraint and blood collection. [ABSTRACT FROM AUTHOR]

This paper reports results from a resume-based field experiment designed to examine employer preferences for job applicants who attended for-profit colleges. For-profit colleges have seen sharp increases in enrollment in recent years despite alternatives, such as public community colleges, being much cheaper. We sent almost 9,000 fictitious resumes of young job applicants who recently completed their schooling to online job postings in six occupational categories and tracked employer callback rates. We find no evidence that employers prefer applicants with resumes listing a for-profit college relative to those whose resumes list either a community college or no college at all. [ABSTRACT FROM AUTHOR]

We developed a coating method to produce functionalized small quantum dots (sQDs), about 9 nm in diameter, that were stable for over a month. We made sQDs in four emission wavelengths, from 527 to 655 nm and with different functional groups. AMPA receptors on live neurons were labeled with sQDs and postsynaptic density proteins were visualized with super-resolution microscopy. Their diffusion behavior indicates that sQDs access the synaptic clefts significantly more often than commercial QDs. [ABSTRACT FROM AUTHOR]

To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in hepatically impaired patients and healthy subjects.Hepatically impaired patients (n = 11) and healthy subjects (n = 11) were individually paired on the basis of gender, age (±10 years) and body weight (±20%) and administered a single dose of oseltamivir (75 mg).Oseltamivir and oseltamivir carboxylateCmax were≤6% and≤19% lower, and their AUC(0,∞) 33% higher and≤19% lower, respectively, in hepatically impaired patients compared with healthy subjects. These changes are within the safety limits for the drug.The metabolism of oseltamivir is not compromised minimally in hepatically impaired patients. No dose adjustment is required in these patients when receiving oseltamivir. [ABSTRACT FROM AUTHOR]

Background: Racial/ethnic minority populations in the United States are consistently underrepresented in genetic research. Large‐scale public participation is required to ensure discoveries from precision medicine research are applicable to everyone. To evaluate views toward and facilitators of participation among minority populations in the United States, we conducted a systematic review of literature. Methods: Six databases were searched for articles published from 2005 to 2018 assessing minority populations' views and/or willingness to participate in genetic research. A thematic framework was applied to extracted data to synthesize findings, and the Socio‐Ecological Model was used to evaluate papers. Results: Review of 2,229 titles and abstracts identified 27 papers (n = 8 qualitative, n = 19 quantitative). Themes included knowledge of genetics, engagement in research, facilitators and barriers to participation, and cultural considerations. Understanding of genetics was low, yet the majority of participants were willing to participate in genetic research among all populations included in the literature (range: 57%–97%). Recommendations for research included utilizing community‐based participatory approaches, evaluating participants' informational needs, incentivizing participation, and providing direct benefits (e.g., genetic test results). Conclusion: Results could influence future study designs that incorporate all levels of the Socio‐Ecological Model and better meet the needs of underrepresented groups, thereby ensuring precision medicine research findings are applicable to all. [ABSTRACT FROM AUTHOR]

Abortion bans premised on fetal pain capacity are this decade's 'partial-birth abortion': a medically suspect anti-choice initiative that can be politically difficult to oppose. No one is 'pro-fetal pain.' But rhetorically, the concept of 'fetal pain' works to conflate the capacity for pain with the experience of pain. If pain justified banning medical procedures, all surgery would be illegal. Pain is a routine side effect of medical practice. What's unethical is unnecessary pain, and that's why the standard medical response to pain is palliation. [ABSTRACT FROM AUTHOR]

Review: 69 refs. [ABSTRACT FROM AUTHOR]