Implementation and Validation of the Roche Light Cycler 480 96-Well Plate Platform as a Real-Time PCR Assay for the Quantitative Detection of Cytomegalovirus (CMV) in Clinical Specimens Using the Luminex MultiCode ASRs System.

Allogenic stem-cell therapies benefit patients in the treatment of multiple diseases; however, the side effects of stem-cell therapies (SCT) derived from the concomitant use of immune suppression agents often include triggering infection diseases. Thus, analysis is required to improve the detection of pathogen infections in SCT. We develop a polymerase chain reaction (PCR)-based methodology for the qualitative real-time DNA detection of cytomegalovirus (CMV), with reference to herpes simplex virus types 1 (HSVI), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) in blood, urine, solid tissues, and cerebrospinal fluid. This real-time PCR of 96-well plate format provides a rapid framework as required by the Food and Drug Administration (FDA) for clinical settings, including the processing of specimens, reagent handling, special safety precautions, quality control criteria and analytical accuracy, precisely reportable range (analyst measurement range), reference range, limit of detection (LOD), analytical specificity established by interference study, and analyte stability. Specifically, we determined the reportable range (analyst measurement range) with the following criteria: CMV copies ≥200 copies/mL; report copy/mL value; CMV copies ≤199 copies/mL; report detected but below quantitative range; CMV copies = 0 with report <200 copies/mL. That is, with reference range, copy numbers (CN) per milliliter (mL) of the LOD were determined by standard curves that correlated Ct value and calibrated standard DNA panels. The three repeats determined that the measuring range was 1E2~1E6 copies/mL. The standard curves show the slopes were within the range -2.99 to -3.65 with R2 ≥ 0.98. High copy (HC) controls were within 0.17-0.18 log differences of DNA copy numbers; (2) low copy (LC) controls were within 0.17-0.18 log differences; (3) LOD was within 0.14-0.15 log differences. As such, we set up a fast, simple, inexpensive, sensitive, and reliable molecular approach for the qualitative detection of CMV pathogens. Conclusion: This real-time PCR of the 96-well plate format provides a rapid framework as required by the FDA for clinical settings

Mathematics Teachers’ Perspectives on Online Professional Development Modules

This study examines mathematics teachers’ perspectives regarding newly developed online professional learning for elementary mathematics teachers of multilingual learners. We examined the responses of 12 teachers on surveys that included both Likert scale and open response items to explore the learning, strengths and weaknesses of the modules. Overall, this study demonstrates the potential for online professional learning at the intersection of language and mathematics and suggests important ways for teacher learning across time to be supported

Institutional Solutions to the Asymmetric Information Problem in Health and Development Services for the Poor

The world’s poorest pay for professional services and thus are in a “market,” whether the services are provided in the public or private sectors. The associated problems of unequal information are particularly acute in undergoverned countries, where state regulation is weak. We systematically review the evidence on solutions to these problems in a variety of professions. Payments by clients are more likely to have a positive effect on quality if they are made through locally-managed organizations rather than directly to individual practitioners, particularly if those organizations have an institutionalized history of other—regarding values and incorporate client participation.UKai

The United States' contribution of plastic waste to land and ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Law, K. L., Starr, N., Siegler, T. R., Jambeck, J. R., Mallos, N. J., & Leonard, G. H. The United States' contribution of plastic waste to land and ocean. Science Advances, 6(44), (2020): eabd0288, doi:10.1126/sciadv.abd0288.Plastic waste affects environmental quality and ecosystem health. In 2010, an estimated 5 to 13 million metric tons (Mt) of plastic waste entered the ocean from both developing countries with insufficient solid waste infrastructure and high-income countries with very high waste generation. We demonstrate that, in 2016, the United States generated the largest amount of plastic waste of any country in the world (42.0 Mt). Between 0.14 and 0.41 Mt of this waste was illegally dumped in the United States, and 0.15 to 0.99 Mt was inadequately managed in countries that imported materials collected in the United States for recycling. Accounting for these contributions, the amount of plastic waste generated in the United States estimated to enter the coastal environment in 2016 was up to five times larger than that estimated for 2010, rendering the United States’ contribution among the highest in the world.This work was funded by Ocean Conservancy through support from the Arthur Vining Davis Foundations

Real-time analysis and display of quantitative measures to track and improve clinical workflow

PURPOSE: Radiotherapy treatment planning is a complex process with multiple, dependent steps involving an interdisciplinary patient care team. Effective communication and real-time tracking of resources and care path activities are key for clinical efficiency and patient safety. MATERIALS AND METHODS: We designed and implemented a secure, interactive web-based dashboard for patient care path, clinical workflow, and resource utilization management. The dashboard enables visualization of resource utilization and tracks progress in a patient\u27s care path from the time of acquisition of the planning CT to the time of treatment in real-time. It integrates with the departmental electronic medical records (EMR) system without the creation and maintenance of a separate database or duplication of work by clinical staff. Performance measures of workflow were calculated. RESULTS: The dashboard implements a standardized clinical workflow and dynamically consolidates real-time information queried from multiple tables in the EMR database over the following views: (1) CT Sims summarizes patient appointment information on the CT simulator and patient load; (2) Linac Sims summarizes patient appointment times, setup history, and notes, and patient load; (3) Task Status lists the clinical tasks associated with a treatment plan, their due date, status and ownership, and patient appointment details; (4) Documents provides the status of all documents in the patients\u27 charts; and (5) Diagnoses and Interventions summarizes prescription information, imaging instructions and whether the plan was approved for treatment. Real-time assessment and quantification of progress and delays in a patient\u27s treatment start were achieved. CONCLUSIONS: This study indicates it is feasible to develop and implement a dashboard, tailored to the needs of an interdisciplinary team, which derives and integrates information from the EMR database for real-time analysis and display of resource utilization and clinical workflow in radiation oncology. The framework developed facilitates informed, data-driven decisions on clinical workflow management as we seek to optimize clinical efficiency and patient safety

A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer

Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC. Methods: Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m2/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned. Results: 11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study. Conclusion: Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis

Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous “black” pigment gallstone formation in germfree Swiss Webster mice

“Black” pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates (“hyperbilirubinbilia”) from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and <1% cholesterol, and had low-grade inflammation, edema, and epithelial hyperplasia. Hemograms were normal, but serum cholesterol was elevated in GF compared with SPF SW mice, and serum glucose levels were positively related to increasing age. Aged GF and SPF SW mice had deficits in gallbladder smooth muscle activity. In response to cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.National Institutes of Health (U.S.) (Training Grant T32-OD10978-26)National Institutes of Health (U.S.) (Training Grant P30-ES002109)Kinship Foundation. Searle Scholars Progra

Prescription dose evaluation for APBI with noninvasive image-guided breast brachytherapy using equivalent uniform dose

ABSTRACT PURPOSE: Noninvasive image-guided breast brachytherapy (NIBB) is an attractive novel approach to deliver accelerated partial breast irradiation (APBI). Calculations of equivalent uniform dose (EUD) were performed to identify the appropriate APBI dose for this technique. METHODS AND MATERIALS: APBI plans were developed for 15 patients: five with threedimensional conformal APBI (3D-CRT), five with multi-lumen intracavitary balloons (m-IBB), and five simulating NIBB treatment. Prescription doses of 34.0 and 38.5 Gy were delivered in 10 fractions for m-IBB and 3D-CRT, respectively. Prescription doses ranging from 34.0 to 38.5 Gy were considered for NIBB. Dose-volume histogram data from all 3D-CRT, m-IBB, and NIBB plans were used to calculate the biologically effective EUD and corresponding EUD to the PTV_eval using the following equation: ). An a/b value of 4.6 Gy was assumed for breast tumor. EUD for varying NIBB prescription doses were compared with EUD values for the other APBI techniques. RESULTS: Mean PTV_eval volume was largest for 3D-CRT (372.9 cm 3 ) and was similar for NIBB and m-IBB (88.7 and 87.2 cm 3 , respectively). The EUD value obtained by prescribing 38.5 Gy with 3D-CRT APBI was 38.6 Gy. The EUD value of 34.0 Gy prescribed with m-IBB was 34.4 Gy. EUD values for NIBB ranged from 33.9 to 38.2 Gy for prescription doses ranging from 34.0 to 38.5 Gy. CONCLUSIONS: Using EUD calculations to compare APBI techniques and treatment doses, a prescription dose of 36.0 Gy in 10 fractions using NIBB has a comparable biologic equivalent dose to other established brachytherapy techniques.

Evidence‐based guideline: Neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome

Introduction: The purpose of this study was to develop an evidence‐based guideline for the use of neuromuscular ultrasound in the diagnosis of carpal tunnel syndrome (CTS). Methods: Two questions were asked: (1) What is the accuracy of median nerve cross‐sectional area enlargement as measured with ultrasound for the diagnosis of CTS? (2) What added value, if any, does neuromuscular ultrasound provide over electrodiagnostic studies alone for the diagnosis of CTS? A systematic review was performed, and studies were classified according to American Academy of Neurology criteria for rating articles of diagnostic accuracy (question 1) and for screening articles (question 2). Results: Neuromuscular ultrasound measurement of median nerve cross‐sectional area at the wrist is accurate and may be offered as a diagnostic test for CTS (Level A). Neuromuscular ultrasound probably adds value to electrodiagnostic studies when diagnosing CTS and should be considered in screening for structural abnormalities at the wrist in those with CTS (Level B). Muscle Nerve 46: 287–293, 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92446/1/23389_ftp.pd

Metabolic acceleration and the evolution of human brain size and life history.

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history