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Development and Flight Test of an Augmented Thrust-Only Flight Control System on an MD-11 Transport Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.; Burken, John J.; Pappas, Drew

1996-01-01

An emergency flight control system using only engine thrust, called Propulsion-Controlled Aircraft (PCA), has been developed and flight tested on an MD-11 airplane. In this thrust-only control system, pilot flight path and track commands and aircraft feedback parameters are used to control the throttles. The PCA system was installed on the MD-11 airplane using software modifications to existing computers. Flight test results show that the PCA system can be used to fly to an airport and safely land a transport airplane with an inoperative flight control system. In up-and-away operation, the PCA system served as an acceptable autopilot capable of extended flight over a range of speeds and altitudes. The PCA approaches, go-arounds, and three landings without the use of any non-nal flight controls have been demonstrated, including instrument landing system-coupled hands-off landings. The PCA operation was used to recover from an upset condition. In addition, PCA was tested at altitude with all three hydraulic systems turned off. This paper reviews the principles of throttles-only flight control; describes the MD-11 airplane and systems; and discusses PCA system development, operation, flight testing, and pilot comments.

75 FR 64984 - Availability of an Environmental Assessment for a Biological Control Agent for Hawkweeds

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Incidence of Cancers of the Lower Stomach Increasing among Younger Americans

MedlinePlus

... by Disqus. blog comments powered by Disqus Featured Posts Advancing Patient Care Through Focused Innovation April 16, 2018, by Norman E. Sharpless, M.D. Study Tests Way to Lower Dose of Prostate Cancer Drug ...

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Pipettor Version 5.x

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thorn, David L.

Code is written in Basic to run using web-available Basic assembler, available at justbasic.com. It drives a set of stepper motors to mechanize the operation of pipetting radioactive solutions within a hot cell, and it communicates via serial port with the C4 stepper controller sold by Arrick, see http://www.arrickrobotics.com/c4md2.html. It is intended to operate stand-alone, that is, the justbasic assembler/application is downloaded onto a PC, the application runs the software program Pipettor, and the instructions are included as comments within the software.

Development and Flight Test of an Emergency Flight Control System Using Only Engine Thrust on an MD-11 Transport Airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Burken, John J.; Maine, Trindel A.; Fullerton, C. Gordon

1997-01-01

An emergency flight control system that uses only engine thrust, called the propulsion-controlled aircraft (PCA) system, was developed and flight tested on an MD-11 airplane. The PCA system is a thrust-only control system, which augments pilot flightpath and track commands with aircraft feedback parameters to control engine thrust. The PCA system was implemented on the MD-11 airplane using only software modifications to existing computers. Results of a 25-hr flight test show that the PCA system can be used to fly to an airport and safely land a transport airplane with an inoperative flight control system. In up-and-away operation, the PCA system served as an acceptable autopilot capable of extended flight over a range of speeds, altitudes, and configurations. PCA approaches, go-arounds, and three landings without the use of any normal flight controls were demonstrated, including ILS-coupled hands-off landings. PCA operation was used to recover from an upset condition. The PCA system was also tested at altitude with all three hydraulic systems turned off. This paper reviews the principles of throttles-only flight control, a history of accidents or incidents in which some or all flight controls were lost, the MD-11 airplane and its systems, PCA system development, operation, flight testing, and pilot comments.

76 FR 46671 - Food Labeling; Gluten-Free Labeling of Foods; Reopening of the Comment Period

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In Praise of Progress

MedlinePlus

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78 FR 23563 - FCC Reduces Backlog of Broadcast Indecency Complaints by 70% (More Than One Million Complaints...

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Dr. William Thornton's views on sleep, dreams, and resuscitation.

PubMed

Paulson, George

2009-01-01

William Thornton, MD, was a polymath who designed the Capitol of the U.S. Capital and the Octagon House, present home of the American Institute of Architecture. He was the founding director of the U.S. Patent Office. His collected papers, which are now preserved at the U.S. Library of Congress, though pruned by the wife who lived almost 40 years after him, are extensive and include comments on science, education, slavery, and politics. His views on sleep and dreaming and his concepts of resuscitation are reviewed as the opinions of an educated man early in the nineteenth century.

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77 FR 54615 - Strategic Management Program; Fiscal Year 2013-2016 Strategic Plan

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Flight Attendant Fatigue: A Quantitative Review of Flight Attendant Comments

DTIC Science & Technology

2011-10-01

Hellesoy, 1994; Hunt & Space, 1994; Nagda & Koontz , 2003; Nesthus et al., 2007; Rayman, 1997; Smolensky, Lee, Mott, & Colligan, 1982; Tashkin...www.boeing. com/commercial/cabinair/ventilation.pdf Nagda, N.L., & Koontz , M.D. (2003). Review of studies on flight attendant health and comfort in

78 FR 76634 - National Institute of Biomedical Imaging and Bioengineering; Notice of Meeting

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"Thirty-Four and Where Am I Going?" A Comment on the Relationship between Teacher Stress and Organisational Change.

ERIC Educational Resources Information Center

Pitt, M. W.; Jennings, L. E.

1984-01-01

Examines sources of stress and coping mechanisms for teachers in the 30-45 year age group in the state of Victoria, Australia. Strategies for relieving stress should focus on the relationship between teachers and the organizations within which they operate. (MD)

75 FR 12546 - Agency Information Collection Activities; Proposed Collection; Comment Request; Cosmetic Labeling...

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Consequentialism and harsh interrogations.

PubMed

Wynia, Matthew K

2005-01-01

With this issue, we begin a regular feature on bioethics and public health. We welcome Matthew K. Wynia, M.D., M.P.H., Director of the Institute for Ethics of the American Medical Association as our new Contributing Editor. If you have comments or suggestions regarding this feature, please email us at manuscript@ bioethics.net.

76 FR 7817 - Announcing Draft Federal Information Processing Standard 180-4, Secure Hash Standard, and Request...

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Molecular Dynamics Simulations of Nucleic Acids. From Tetranucleotides to the Ribosome.

PubMed

Šponer, Jiří; Banáš, Pavel; Jurečka, Petr; Zgarbová, Marie; Kührová, Petra; Havrila, Marek; Krepl, Miroslav; Stadlbauer, Petr; Otyepka, Michal

2014-05-15

We present a brief overview of explicit solvent molecular dynamics (MD) simulations of nucleic acids. We explain physical chemistry limitations of the simulations, namely, the molecular mechanics (MM) force field (FF) approximation and limited time scale. Further, we discuss relations and differences between simulations and experiments, compare standard and enhanced sampling simulations, discuss the role of starting structures, comment on different versions of nucleic acid FFs, and relate MM computations with contemporary quantum chemistry. Despite its limitations, we show that MD is a powerful technique for studying the structural dynamics of nucleic acids with a fast growing potential that substantially complements experimental results and aids their interpretation.

75 FR 9605 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

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76 FR 80448 - VASRD Forum-Improving VA's Disability Evaluation Criteria for Neurological Conditions and...

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Biomass Program 2007 Program Peer Review - Feedstock Platform Summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This document discloses the comments provided by a review panel at the U.S. Department of Energy Office of the Biomass Program Peer Review held on November 15-16, 2007 in Baltimore, MD and the Feedstock Platform Portfolio Peer Review held on August 21st through 23rd in Washington D.C.

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Human male infertility and its genetic causes.

PubMed

Miyamoto, Toshinobu; Minase, Gaku; Shin, Takeshi; Ueda, Hiroto; Okada, Hiroshi; Sengoku, Kazuo

2017-04-01

Infertility affects about 15% of couples who wish to have children and half of these cases are associated with male factors. Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations/deletions of several Y chromosome genes. Many researchers have analyzed genes in the AZF region on the Y chromosome; however, in 2003 the SYCP3 gene on chromosome 12 (12q23) was identified as causing azoospermia by meiotic arrest through a point mutation. We mainly describe the SYCP3 and PLK4 genes that we have studied in our laboratory, and add comments on other genes associated with human male infertility. Up to now, The 17 genes causing male infertility by their mutation have been reported in human. Infertility caused by nonobstructive azoospermia (NOA) is very important in the field of assisted reproductive technology. Even with the aid of chromosomal analysis, ultrasonography of the testis, and detailed endocrinology, only MD-TESE can confirm the presence of immature spermatozoa in the testes. We strongly hope that these studies help clinics avoid ineffective MD-TESE procedures.

Response to "Comment on `Solitonic and chaotic behaviors for the nonlinear dust-acoustic waves in a magnetized dusty plasma'" [Phys. Plasmas 24, 094701 (2017)

NASA Astrophysics Data System (ADS)

Zhen, Hui-Ling; Tian, Bo; Xie, Xi-Yang; Wu, Xiao-Yu; Wen, Xiao-Yong

2018-02-01

On our previous construction [H. L. Zhen et al., Phys. Plasmas 23, 052301 (2016)] of the soliton solutions of a model describing the dynamics of the dust particles in a weakly ionized, collisional dusty plasma comprised of the negatively charged cold dust particles, hot ions, hot electrons, and stationary neutrals in the presence of an external static magnetic field, Ali et al. [Phys. Plasmas 24, 094701 (2017)] have commented that there exists a different form of Eq. (4) from that shown in Zhen et al. [Phys. Plasmas 23, 052301 (2016)] and that certain interesting phenomena with the dust neutral collision frequency ν0>0 are ignored in Zhen et al. [Phys. Plasmas 23, 052301 (2016)]. In this Reply, according to the transformation given by the Ali et al. [Phys. Plasmas 24, 094701 (2017)] comment, we present some one-, two-, and N-soliton solutions which have not been obtained in the Ali et al. [Phys. Plasmas 24, 094701 (2017)] comment. We point out that our previous solutions in Zhen et al. [Phys. Plasmas 23, 052301 (2016)] are still valid because of the similarity between the two dispersion relations of previous solutions in Zhen et al. [Phys. Plasmas 23, 052301 (2016)] and the solutions presented in this Reply. Based on our soliton solutions in this Reply, it is found that the soliton amplitude is inversely related to Zd and B0, but positively related to md and α, where α refers to the coefficient of the nonlinear term, Zd and md are the charge number and mass of a dust particle, respectively, B0 represents the strength of the external static magnetic field. We also find that the two solitons are always in parallel during the propagation.

75 FR 25267 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

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77 FR 27463 - Device Improvements for Pediatric X-Ray Imaging; Public Meeting; Request for Comments

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2012-05-10

... pediatric x-ray imaging that may benefit from standards development or further research. DATES: Date and... held at FDA White Oak Campus, 10903 New Hampshire Ave., Building 31 Conference Center, the Great Room..., Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 4527, Silver Spring, MD 20993...

Biomass Program 2007 Program Peer Review - Full Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This document summarizes the comments provided by the peer reviewers at the U.S. Department of Energy (DOE) Biomass Program’s Peer Review meeting, held on November 14-15, 2007 in Baltimore, MD and Platform Reviews conducted over the summer of 2007. The Platform Reviews provide evaluations of the Program’s projects in applied research, development, and demonstration.

76 FR 4997 - Medicare Program; Inpatient Psychiatric Facilities Prospective Payment System-Update for Rate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

.... Repeating this step for other periods produces a series of market basket levels over time. Dividing an index..., P.O. Box 8010, Baltimore, MD 21244-1850. Please allow sufficient time for mailed comments to be...); interrupted stays; and a per treatment adjustment for patients who undergo ECT. A complete discussion of the...

77 FR 52741 - MDEpiNet 2012 Annual Meeting: The Medical Device Epidemiology Network as a Partnership for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

...) proposed partnership structure and governance; (3) MDEpiNet as a framework for medical device postmarket.... 1061, Rockville, MD 20852 or electronic comments to http://www.regulations.gov . It is only necessary... transcript is available, it will be accessible at http://www.regulations.gov . It may be viewed at the...

77 FR 29966 - Marine Mammals; File No. 17157

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2012-05-21

..., MD 20910; phone (301) 427-8401; fax (301) 713-0376; and Southeast Region, NMFS, 263 13th Avenue South.... Comments may also be submitted by facsimile to (301) 713-0376, or by email to [email protected] 1969 (42 U.S.C. 4321 et seq.), an initial determination has been made that the activities proposed are...

75 FR 32484 - Array-Based Cytogenetic Tests: Questions on Performance Evaluation, Result Reporting and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0259... meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA) is announcing the following.... 4321, Silver Spring, MD 20903, 301-796- 5661, e-mail: [email protected]fda.hhs.gov ; or Zivana Tezak, Food...

Evaluation of Physician and Nurse Dyad Training Procedures to Deliver a Palliative and End-of-Life Communication Intervention to Parents of Children with a Brain Tumor

PubMed Central

Hendricks-Ferguson, Verna L.; Kane, Javier R.; Pradhan, Kamnesh R.; Shih, Chie-Schin; Gauvain, Karen M.; Baker, Justin N.; Haase, Joan E.

2017-01-01

When a child’s prognosis is poor, physicians and nurses (MDs/RNs) often struggle with initiating discussions about palliative and end-of-life care (PC/EOL) early in the course of illness trajectory. We describe evaluation of training procedures used to prepare MD/RN dyads to deliver an intervention entitled: Communication Plan: Early Through End of Life (COMPLETE) intervention. Our training was delivered to 5 pediatric neuro-oncologists and 8 pediatric nurses by a team of expert consultants (i.e., in medical ethics, communication, and PC/EOL) and parent advisors. Although half of the group received training in a 1-day program and half in a 2-day program, content for all participants included 4 modules: family assessment, goal-directed treatment planning, anticipatory guidance, and staff communication and follow-up. Evaluations included dichotomous ratings and qualitative comments on content, reflection, and skills practice for each module. Positive aspects of our training included parent advisers’ insights, emphasis on hope and non-abandonment messages, written materials to facilitate PC/EOL communication, and an MD/RN dyad approach. Lessons learned and challenges related to our training procedures will be described. Overall, the MDs and RNs reported that our PC/EOL communication-training procedures were helpful and useful. Future investigators should carefully plan training procedures for PC/EOL communication interventions. PMID:25623029

76 FR 1381 - Special Local Regulations for Marine Events; Potomac River, Charles County, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-10

... document so that we can contact you if we have questions regarding your submission. To submit your comment... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... ADDRESSES) explaining why you think it qualifies and how and to what degree this rule would economically...

78 FR 20066 - Special Local Regulations; Marine Events, Spa Creek and Annapolis Harbor; Annapolis, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

... document so that we can contact you if we have questions regarding your submission. To submit your comment... do not now plan to hold a public meeting. But you may submit a request for one, using one of the... that do not individually or cumulatively have a significant effect on the human environment. This...

Barriers to pediatric pain management: a nursing perspective.

PubMed

Czarnecki, Michelle L; Simon, Katherine; Thompson, Jamie J; Armus, Cheryl L; Hanson, Tom C; Berg, Kristin A; Petrie, Jodie L; Xiang, Qun; Malin, Shelly

2011-09-01

This study describes strategies used by the Joint Clinical Practice Council of Children's Hospital of Wisconsin to identify barriers perceived as interfering with nurses' (RNs) ability to provide optimal pain management. A survey was used to ascertain how nurses described optimal pain management and how much nurses perceived potential barriers as interfering with their ability to provide that level of care. The survey, "Barriers to Optimal Pain management" (adapted from Van Hulle Vincent & Denyes, 2004), was distributed to all RNs working in all patient care settings. Two hundred seventy-two surveys were returned. The five most significant barriers identified were insufficient physician (MD) orders, insufficient MD orders before procedures, insufficient time to premedicate patients before procedures, the perception of a low priority given to pain management by medical staff, and parents' reluctance to have patients receive pain medication. Additional barriers were identified through narrative comments. Information regarding the impact of the Acute Pain Service on patient care, RNs' ability to overcome barriers, and RNs' perception of current pain management practices is included, as are several specific interventions aimed at improving or ultimately eliminating identified barriers. Copyright © 2011 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

76 FR 23606 - Submission for OMB Review; Comment Request; National Institutes of Health Loan Repayment Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... National Institutes of Health (NIH) has submitted to the Office of Management and Budget (OMB) a request to... financial assistance, in the form of educational loan repayment, to M.D., PhD, Pharm.D., D.D.S., D.M.D..., directly to financial institutions. The information proposed for collection will be used by the Division of...

76 FR 67207 - Certain Wiper Blades; Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... complaint names as respondents ADM21 Co., Ltd. of Korea; ADM21 Co. (North America) Ltd. of NJ; Alberee Products, Inc. of MD; API Korea Co., Ltd. of Korea; Cequent Consumer Products, Inc. of OH; Corea Autoparts Producing Corporation of South Korea; Danyang UPC Auto Parts Co., Ltd. of China; Fu-Gang Co., Ltd. of Taiwan...

77 FR 25649 - Special Local Regulations for Marine Events; Patuxent River, Solomons, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

..., an email address, or a telephone number in the body of your document so that we can contact you if we... Meeting We do not now plan to hold a public meeting. But you may submit a request for one, using one of..., please submit a comment (see ADDRESSES) explaining why you think it qualifies and how and to what degree...

76 FR 14796 - Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines AGENCY: Federal... airworthiness directive (AD) for General Electric Company (GE) CF6-45 and CF6-50 series turbofan engines. That..., and MD-10- 30F. The commenter stated that the proposed AD only listed these airplanes as a series. We...

Evaluation of Physician and Nurse Dyad Training Procedures to Deliver a Palliative and End-of-Life Communication Intervention to Parents of Children with a Brain Tumor.

PubMed

Hendricks-Ferguson, Verna L; Kane, Javier R; Pradhan, Kamnesh R; Shih, Chie-Schin; Gauvain, Karen M; Baker, Justin N; Haase, Joan E

2015-01-01

When a child's prognosis is poor, physicians and nurses (MDs/RNs) often struggle with initiating discussions about palliative and end-of-life care (PC/EOL) early in the course of illness trajectory. We describe evaluation of training procedures used to prepare MD/RN dyads to deliver an intervention entitled: Communication Plan: Early Through End of Life (COMPLETE) intervention. Our training was delivered to 5 pediatric neuro-oncologists and 8 pediatric nurses by a team of expert consultants (i.e., in medical ethics, communication, and PC/EOL) and parent advisors. Although half of the group received training in a 1-day program and half in a 2-day program, content for all participants included 4 modules: family assessment, goal-directed treatment planning, anticipatory guidance, and staff communication and follow-up. Evaluations included dichotomous ratings and qualitative comments on content, reflection, and skills practice for each module. Positive aspects of our training included parent advisers' insights, emphasis on hope and non-abandonment messages, written materials to facilitate PC/EOL communication, and an MD/RN dyad approach. Lessons learned and challenges related to our training procedures will be described. Overall, the MDs and RNs reported that our PC/EOL communication-training procedures were helpful and useful. Future investigators should carefully plan training procedures for PC/EOL communication interventions. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

78 FR 36788 - Proposed Collection; 60-Day Comment Request; Awareness and Beliefs About Cancer Survey, National...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

...In compliance with the requirement of Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, for opportunity for public comment on proposed data collection projects, the National Cancer Institute (NCI), National Institutes of Health (NIH) will publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Written comments and/or suggestions from the public and affected agencies are invited on one or more of the following points: (1) Whether the proposed collection of information is necessary for the proper performance of the function of the agency, including whether the information will have practical utility; (2) The accuracy of the agency's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) Ways to enhance the quality, utility, and clarity of the information to be collected; and (4) Ways to minimize the burden of the collection of information on those who are to respond, including the use of appropriate automated, electronic, mechanical, or other technological collection techniques or other forms of information technology. To Submit Comments and for Further Information: To obtain a copy of the data collection plans and instruments, submit comments in writing, or request more information on the proposed project, contact: Sarah Kobrin, Division of Cancer Control and Population Sciences, 9609 Medical Center Dr., MSC 9761, Rockville, MD 20852, or call non-toll- free number 240-276-6931 or Email your request, including your address to: [email protected] Formal requests for additional plans and instruments must be requested in writing. Comment Due Date: Comments regarding this information collection are best assured of having their full effect if received within 60 days of the date of this publication. Proposed Collection: Awareness and Beliefs about Cancer Survey, 0925-NEW, National Cancer Institute (NCI), National Institutes of Health (NIH). Need and Use of Information Collection: The objective of the study is gather data about American adults' awareness and beliefs about cancer. The ultimate goal is to determine how individuals' perceptions of cancer may influence their decisions to report signs and symptoms to health care providers, perhaps affecting the disease stage of diagnosis and the effectiveness of treatment. Data will be collected from approximately 2,000 adults aged 50 years or older across the United States for the NCI Awareness and Beliefs about Cancer survey over a one-year period. OMB approval is requested for one year. There are no costs to respondents other than their time. The total estimated annualized burden hours are 1,334.

Preliminary Reports, Memoranda and Technical Notes of the Materials Research Council Summer Conference, La Jolla, California. Volume II

DTIC Science & Technology

1981-07-01

C. McGill and J. 0. McCaldin ..... ............. .. 160 Diffusional Instability of p /n Heterojunctions J. J. Gilman...Preliminary Ideas on a Ductile-Brittle Transition in Fe-Si Single Crystals R. Thomson and J. P . Hirth. . . . . . . . . . . . . . . . 199 Comment on a...Baltimore, MD 21218 Professor Alan J. Heeger Department of Physics/El University of Pennsylvania Philadelphia, PA 19104 Professor John P . Hirth

A Comparison of HAART Outcomes between the US Military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS)

DTIC Science & Technology

2013-05-01

Acknowledgments The IDCRP HIV Working Group includes: Susan Banks, RN, CAPT Mary Bavaro, MD, Ionut Bebu, PhD, Helen Chun, MD, Nancy Crum- Cianflone, MD, MPH...Cathy Decker, MD, Conner Eggleston, LTC Tomas Ferguson, MD, COL Susan Fraser, MD, MAJ Joshua Hartzell, MD, MAJ Joshua Hawley, MD, LTC Gunther Hsue, MD

Fitwits MD™: an office-based tool and games for conversations about obesity with 9- to 12-year-old children.

PubMed

McGaffey, Ann L; Abatemarco, Diane J; Jewell, Ilene Katz; Fidler, Susan K; Hughes, Kristin

2011-01-01

Physician feelings of ineffectiveness and family-related barriers hamper childhood obesity discussions. Physicians desire appealing, time-efficient tools to frame and sensitively address obesity, body mass index, physical activity, nutrition, and portion size. Our university design-led coalition codeveloped tools and games for this purpose. In this feasibility study, we evaluated physician-level counseling of 9- to 12-year-old children and their parents/caretakers using Fitwits MD (Carnegie Mellon University School of Design, Pittsburgh, PA), a brief, structured intervention with flashcards and take-home games. Residency-based physicians in three low- to mid-level socioeconomic urban offices provided self-report data over 8 months through surveys, comment cards, and interviews. We recruited 33 physicians and 93 preadolescents and families. Child-centered key messages resulted in 7-minute conversations, on average. For those physicians who used Fitwits MD, 96% felt improved comfort and competence and 78% noted barrier reduction. Fitwits MD improved residency-based physician self-efficacy and emphasized important health education topics regarding office-based childhood obesity discussions with preadolescents and parents/caretakers.

An innovative Near-Peer Mentoring Model for Undergraduate and Secondary Students: STEM Focus

DTIC Science & Technology

2014-03-14

searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments...568 Doughten Drive,Fort Detrick,MD,21702-5010 8. PERFORMING ORGANIZATION REPORT NUMBER N /A 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES...applications, research background, experience with youth, and interviews. They ranged in age from 18 to 25 (M = 21) and were either undergraduate ( n = 7

Rehabilitation that incorporates virtual reality is more effective than standard rehabilitation for improving walking speed, balance and mobility after stroke: a systematic review.

PubMed

Corbetta, Davide; Imeri, Federico; Gatti, Roberto

2015-07-01

In people after stroke, does virtual reality based rehabilitation (VRBR) improve walking speed, balance and mobility more than the same duration of standard rehabilitation? In people after stroke, does adding extra VRBR to standard rehabilitation improve the effects on gait, balance and mobility? Systematic review with meta-analysis of randomised trials. Adults with a clinical diagnosis of stroke. Eligible trials had to include one these comparisons: VRBR replacing some or all of standard rehabilitation or VRBR used as extra rehabilitation time added to a standard rehabilitation regimen. Walking speed, balance, mobility and adverse events. In total, 15 trials involving 341 participants were included. When VRBR replaced some or all of the standard rehabilitation, there were statistically significant benefits in walking speed (MD 0.15 m/s, 95% CI 0.10 to 0.19), balance (MD 2.1 points on the Berg Balance Scale, 95% CI 1.8 to 2.5) and mobility (MD 2.3 seconds on the Timed Up and Go test, 95% CI 1.2 to 3.4). When VRBR was added to standard rehabilitation, mobility showed a significant benefit (0.7 seconds on the Timed Up and Go test, 95% CI 0.4 to 1.1), but insufficient evidence was found to comment about walking speed (one trial) and balance (high heterogeneity). Substituting some or all of a standard rehabilitation regimen with VRBR elicits greater benefits in walking speed, balance and mobility in people with stroke. Although the benefits are small, the extra cost of applying virtual reality to standard rehabilitation is also small, especially when spread over many patients in a clinic. Adding extra VRBR time to standard rehabilitation also has some benefits; further research is needed to determine if these benefits are clinically worthwhile. Copyright © 2015 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

The R2R3-MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple.

PubMed

Hu, Da-Gang; Li, Yuan-Yuan; Zhang, Quan-Yan; Li, Ming; Sun, Cui-Hui; Yu, Jian-Qiang; Hao, Yu-Jin

2017-08-01

Malate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate-metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Evaluation of microwave landing system approaches in a wide-body transport simulator

NASA Technical Reports Server (NTRS)

Summers, L. G.; Feather, J. B.

1992-01-01

The objective of this study was to determine the suitability of flying complex curved approaches using the microwave landing system (MLS) with a wide-body transport aircraft. Fifty pilots in crews of two participated in the evaluation using a fixed-base simulator that emulated an MD-11 aircraft. Five approaches, consisting of one straight-in approach and four curved approaches, were flown by the pilots using a flight director. The test variables include the following: (1) manual and autothrottles; (2) wind direction; and (3) type of navigation display. The navigation display was either a map or a horizontal situation indicator (HSI). A complex wind that changed direction and speed with altitude, and included moderate turbulence, was used. Visibility conditions were Cat 1 or better. Subjective test data included pilot responses to questionnaires and pilot comments. Objective performance data included tracking accuracy, position error at decision height, and control activity. Results of the evaluation indicate that flying curved MLS approaches with a wide-body transport aircraft is operationally acceptable, depending upon the length of the final straight segment and the complexity of the approach.

Apple FLOWERING LOCUS T proteins interact with transcription factors implicated in cell growth and organ development.

PubMed

Mimida, Naozumi; Kidou, Shin-Ichiro; Iwanami, Hiroshi; Moriya, Shigeki; Abe, Kazuyuki; Voogd, Charlotte; Varkonyi-Gasic, Erika; Kotoda, Nobuhiro

2011-05-01

Understanding the flowering process in apple (Malus × domestica Borkh.) is essential for developing methods to shorten the breeding period and regulate fruit yield. It is known that FLOWERING LOCUS T (FT) acts as a transmissible floral inducer in the Arabidopsis flowering network system. To clarify the molecular network of two apple FT orthologues, MdFT1 and MdFT2, we performed a yeast two-hybrid screen to identify proteins that interact with MdFT1. We identified several transcription factors, including two members of the TCP (TEOSINTE BRANCHED1, CYCLOIDEA and PROLIFERATING CELL FACTORs) family, designated MdTCP2 and MdTCP4, and an Arabidopsis thaliana VOZ1 (Vascular plant One Zinc finger protein1)-like protein, designated MdVOZ1. MdTCP2 and MdVOZ1 also interacted with MdFT2 in yeast. The expression domain of MdTCP2 and MdVOZ1 partially overlapped with that of MdFT1 and MdFT2, most strikingly in apple fruit tissue, further suggesting a potential interaction in vivo. Constitutive expression of MdTCP2, MdTCP4 and MdVOZ1 in Arabidopsis affected plant size, leaf morphology and the formation of leaf primordia on the adaxial side of cotyledons. On the other hand, chimeric MdTCP2, MdTCP4 and MdVOZ1 repressors that included the ethylene-responsive transcription factors (ERF)-associated amphiphilic repression (EAR) domain motif influenced reproduction and inflorescence architecture in transgenic Arabidopsis. These results suggest that MdFT1 and/or MdFT2 might be involved in the regulation of cellular proliferation and the formation of new tissues and that they might affect leaf and fruit development by interacting with TCP- and VOZ-family proteins. DDBJ accession nos. AB531019 (MdTCP2a mRNA), AB531020 (MdTCP2b mRNA), AB531021 (MdTCP4a mRNA), AB531022 (MdTCP4b mRNA) and AB531023 (MdVOZ1a mRNA). © The Author 2011. Published by Oxford University Press. All rights reserved.

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

PubMed

Benson, Constance A; Currier, Judith S; Del Rio, Carlos; Gallant, Joel E; Gulick, Roy M; Marrazzo, Jeanne M; Richman, Douglas D; Saag, Michael S; Schooley, Robert T; Volberding, Paul A

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.

Graduate Education and Simulation Training for CBRNE Disasters Using a Multimodal Approach to Learning. Part 2: Education and Training from the Perspectives of Educators and Students

DTIC Science & Technology

2013-08-01

anesthetized NHPs exposed to the carbamate nerve-agent simulant physostigmine, which is FDA-approved for the diagnosis and treatment of myasthenia ... gravis . Physostigmine is a short-acting drug that reliably induces the cholinergic signs of increased secretions (lacrimation, hypersalivation...the experience. One insightful comment is provided below. “As an MD, I have treated myasthenia crisis and delirium tremens. I can say definitely

SocioEconomic Characteristics of the All Volunteer Force: Evidence from the National Longitudinal Survey, 1979

DTIC Science & Technology

1982-02-01

Fredland 0>-and DTIC Roger D. Little ELECTE 1 Economics Department S JUL 6 1982 U.S. Naval Academy Annapolis, Maryland 21402 D DISTRIBUTION STATEMENT A...NATIONAL LONGITUDINAL SURVEY, 1979 by J. Eric Fredland and Roger D. Little Economics Department U.S. Naval Academy Annapolis, MD 21402 ii; DISTRIBUTION...comments, Steven Lerch for technical assis- tance, and Doris Keating for typing support. i. 4 I• I SECURITY CLASSIFICATIONI OF THIS PAGE (When Dal* EnterNAU

Light Quark Mass Ratios (mu:md:ms) from Meson and Baryon Mass Splittings

NASA Astrophysics Data System (ADS)

Minkowski, Peter

2013-08-01

The basis of the material discussed is our work in collaboration with Arnulfo Zepeda from 1979 [Nucl. Phys. B164, 25 (1980)]. The ingredients and consequences of this work will be presented, and compared with results obtained from QCD sum rules and lattice simulations of QCD in accordance with chiral expansions. An up-to-date conclusion will not be possible in this paper, but some comments towards such goal will be given in a concluding section.

Apple F-Box Protein MdMAX2 Regulates Plant Photomorphogenesis and Stress Response.

PubMed

An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2016-01-01

MAX2 (MORE AXILLARY GROWTH2) is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length. Further study indicated that MdMAX2 might promote plant photomorphogenesis by affecting the auxin signaling as well as other plant hormones. Transcripts of MdMAX2 were noticeably up-regulated in response to NaCl and Mannitol treatments. Moreover, compared with the wild-type, the MdMAX2 -overexpressing apple calli and Arabidopsis exhibited increased tolerance to salt and drought stresses. Taken together, these results suggest that MdMAX2 plays a positive regulatory role in plant photomorphogenesis and stress response.

Molecular characterization of FLOWERING LOCUS T-like genes of apple (Malus x domestica Borkh.).

PubMed

Kotoda, Nobuhiro; Hayashi, Hidehiro; Suzuki, Motoko; Igarashi, Megumi; Hatsuyama, Yoshimichi; Kidou, Shin-Ichiro; Igasaki, Tomohiro; Nishiguchi, Mitsuru; Yano, Kanako; Shimizu, Tokurou; Takahashi, Sae; Iwanami, Hiroshi; Moriya, Shigeki; Abe, Kazuyuki

2010-04-01

The two FLOWERING LOCUS T (FT)-like genes of apple (Malus x domestica Borkh.), MdFT1 and MdFT2, have been isolated and characterized. MdFT1 and MdFT2 were mapped, respectively, on distinct linkage groups (LGs) with partial homoeology, LG 12 and LG 4. The expression pattern of MdFT1 and MdFT2 differed in that MdFT1 was expressed mainly in apical buds of fruit-bearing shoots in the adult phase, with little expression in the juvenile tissues, whereas MdFT2 was expressed mainly in reproductive organs, including flower buds and young fruit. On the other hand, both genes had the potential to induce early flowering since transgenic Arabidopsis, which ectopically expressed MdFT1 or MdFT2, flowered earlier than wild-type plants. Furthermore, overexpression of MdFT1 conferred precocious flowering in apple, with altered expression of other endogenous genes, such as MdMADS12. These results suggest that MdFT1 could function to promote flowering by altering the expression of those genes and that, at least, other genes may play an important role as well in the regulation of flowering in apple. The long juvenile period of fruit trees prevents early cropping and efficient breeding. Our findings will be useful information to unveil the molecular mechanism of flowering and to develop methods to shorten the juvenile period in various fruit trees, including apple.

Comprehensive Genomic Identification and Expression Analysis of the Phosphate Transporter (PHT) Gene Family in Apple

PubMed Central

Sun, Tingting; Li, Mingjun; Shao, Yun; Yu, Lingyan; Ma, Fengwang

2017-01-01

Elemental phosphorus (Pi) is essential to plant growth and development. The family of phosphate transporters (PHTs) mediates the uptake and translocation of Pi inside the plants. Members include five sub-cellular phosphate transporters that play different roles in Pi uptake and transport. We searched the Genome Database for Rosaceae and identified five clusters of phosphate transporters in apple (Malus domestica), including 37 putative genes. The MdPHT1 family contains 14 genes while MdPHT2 has two, MdPHT3 has seven, MdPHT4 has 11, and MdPHT5 has three. Our overview of this gene family focused on structure, chromosomal distribution and localization, phylogenies, and motifs. These genes displayed differential expression patterns in various tissues. For example, expression was high for MdPHT1;12, MdPHT3;6, and MdPHT3;7 in the roots, and was also increased in response to low-phosphorus conditions. In contrast, MdPHT4;1, MdPHT4;4, and MdPHT4;10 were expressed only in the leaves while transcript levels of MdPHT1;4, MdPHT1;12, and MdPHT5;3 were highest in flowers. In general, these 37 genes were regulated significantly in either roots or leaves in response to the imposition of phosphorus and/or drought stress. The results suggest that members of the PHT family function in plant adaptations to adverse growing environments. Our study will lay a foundation for better understanding the PHT family evolution and exploring genes of interest for genetic improvement in apple. PMID:28424713

Comment on "Relating side chain organization of PNIPAm with its conformation in aqueous methanol" by D. Mukherji, M. Wagner, M. D. Watson, S. Winzen, T. E. de Oliveira, C. M. Marques and K. Kremer, Soft Matter, 2016, 12, 7995.

PubMed

Pica, Andrea; Graziano, Giuseppe

2017-11-01

In a recent article, Kremer and co-workers have combined NMR measurements and very long, all-atom MD simulations to strengthen their original claim that PNIPAM cononsolvency in water-methanol solutions is driven by the ability of MeOH molecules to bridge different monomers far away along the polymeric chain. In this comment, the results presented by Kremer and co-workers are reviewed, analyzed, and questioned regarding their ability to provide support to the bridging mechanism. Here, some pieces of evidence are provided to show that: (1) the solvent-excluded volume effect plays always a fundamental role in polymer collapse; (2) PNIPAM cononsolvency is caused by the geometric-energetic frustration experienced by the polymer when it can interact with both water and methanol molecules at the same time.

Childhood Trauma and Minimization/Denial in People with and without a Severe Mental Disorder.

PubMed

Church, Chelsea; Andreassen, Ole A; Lorentzen, Steinar; Melle, Ingrid; Aas, Monica

2017-01-01

Background: Childhood trauma has garnered extensive research concerning its role in the psychopathology of mental disorders, including psychosis. The Childhood Trauma Questionnaire (CTQ) utilizes a minimization/denial (MD) scale to denote potential under-reporters of trauma, yet MD scores are infrequently reported and validations of the scale are lacking in the literature. Elucidate differences in MD between patients with severe mental disorders to healthy individuals, and secondly, investigate if MD influences reports of childhood trauma between the groups. Methods: We included 621 patients with a DSM-schizophrenia spectrum, bipolar spectrum diagnosis, or major depression disorder with psychotic features and 299 healthy controls as part of the NORMENT study in Oslo, Norway. History of childhood trauma was obtained using the CTQ. Clinical diagnoses were assessed using the Structured Clinical Interview for DSM Disorders. Results: A significantly greater proportion of healthy controls (42.8%) had a positive MD score compared to patients (26.7%). When controlling for MD, the patient group still exhibited elevated reports of childhood trauma compared to controls (Cohen's d = 1.27), concordant with reports of childhood trauma being more frequently reported in a population of severe mental disorders. Conclusion: Elevated MD in the healthy control group could suggest an enhanced self-serving bias, potentially attenuated in the psychiatric group. Clinicians and researchers would benefit from including the MD component of CTQ when assessing retrospective information on childhood trauma to rule out potential effect of MD.

New Therapeutic Modalities of Retinal Laser Injury.

DTIC Science & Technology

1992-03-31

Clawticarroni New Therapeutic Modalities for Retinal Laser Injury 1 2 . PERSONAL AUTHOR(S) Tim T.Lar. Ph.D., .and Mark Q.M. Tso. M.D. 13a. TYPE OF...Experimental treatment of retinal laser Injury 4 1.3: Clinical therapy 4 1.4: Our hypothesis and approaches 4 Chapter 2 : Accidental laser Injury to the...human retina 7 2.1: Introduction 7 2.2: Case 1 7 2.3: Case 2 8 2.4: General comments 9 2.5: Clinical course 10 2.6: Implications 10 Chapter 3: Sub

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening[OPEN

PubMed Central

Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui

2017-01-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1. This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1. Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. PMID:28550149

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

PubMed

Li, Tong; Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui; Wang, Aide

2017-06-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple ( Malus domestica ). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1 , an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2 , encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3 , encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. © 2017 American Society of Plant Biologists. All rights reserved.

MdMYB1 Regulates Anthocyanin and Malate Accumulation by Directly Facilitating Their Transport into Vacuoles in Apples1[OPEN

PubMed Central

Hu, Da-Gang; Sun, Cui-Hui; Ma, Qi-Jun; You, Chun-Xiang; Hao, Yu-Jin

2016-01-01

Tonoplast transporters, including proton pumps and secondary transporters, are essential for plant cell function and for quality formation of fleshy fruits and ornamentals. Vacuolar transport of anthocyanins, malate, and other metabolites is directly or indirectly dependent on the H+-pumping activities of vacuolar H+-ATPase (VHA) and/or vacuolar H+-pyrophosphatase, but how these proton pumps are regulated in modulating vacuolar transport is largely unknown. Here, we report a transcription factor, MdMYB1, in apples that binds to the promoters of two genes encoding the B subunits of VHA, MdVHA-B1 and MdVHA-B2, to transcriptionally activate its expression, thereby enhancing VHA activity. A series of transgenic analyses in apples demonstrates that MdMYB1/10 controls cell pH and anthocyanin accumulation partially by regulating MdVHA-B1 and MdVHA-B2. Furthermore, several other direct target genes of MdMYB10 are identified, including MdVHA-E2, MdVHP1, MdMATE-LIKE1, and MdtDT, which are involved in H+-pumping or in the transport of anthocyanins and malates into vacuoles. Finally, we show that the mechanism by which MYB controls malate and anthocyanin accumulation in apples also operates in Arabidopsis (Arabidopsis thaliana). These findings provide novel insights into how MYB transcription factors directly modulate the vacuolar transport system in addition to anthocyanin biosynthesis, consequently controlling organ coloration and cell pH in plants. PMID:26637549

MdMYB1 Regulates Anthocyanin and Malate Accumulation by Directly Facilitating Their Transport into Vacuoles in Apples.

PubMed

Hu, Da-Gang; Sun, Cui-Hui; Ma, Qi-Jun; You, Chun-Xiang; Cheng, Lailiang; Hao, Yu-Jin

2016-03-01

Tonoplast transporters, including proton pumps and secondary transporters, are essential for plant cell function and for quality formation of fleshy fruits and ornamentals. Vacuolar transport of anthocyanins, malate, and other metabolites is directly or indirectly dependent on the H(+)-pumping activities of vacuolar H(+)-ATPase (VHA) and/or vacuolar H(+)-pyrophosphatase, but how these proton pumps are regulated in modulating vacuolar transport is largely unknown. Here, we report a transcription factor, MdMYB1, in apples that binds to the promoters of two genes encoding the B subunits of VHA, MdVHA-B1 and MdVHA-B2, to transcriptionally activate its expression, thereby enhancing VHA activity. A series of transgenic analyses in apples demonstrates that MdMYB1/10 controls cell pH and anthocyanin accumulation partially by regulating MdVHA-B1 and MdVHA-B2. Furthermore, several other direct target genes of MdMYB10 are identified, including MdVHA-E2, MdVHP1, MdMATE-LIKE1, and MdtDT, which are involved in H(+)-pumping or in the transport of anthocyanins and malates into vacuoles. Finally, we show that the mechanism by which MYB controls malate and anthocyanin accumulation in apples also operates in Arabidopsis (Arabidopsis thaliana). These findings provide novel insights into how MYB transcription factors directly modulate the vacuolar transport system in addition to anthocyanin biosynthesis, consequently controlling organ coloration and cell pH in plants. © 2016 American Society of Plant Biologists. All Rights Reserved.

Evaluation of Factors Affecting Vaccine Efficacy of Recombinant Marek's Disease Virus Lacking the Meq Oncogene in Chickens

USDA-ARS?s Scientific Manuscript database

We have previously reported that deletion of Meq gene from oncogenic rMd5 virus rendered it apathogenic for chickens. Here we examined multiple factors affecting Marek’s disease (MD) vaccine efficacy of this non-pathogenic recombinant Meq null rMd5 virus (rMd5deltaMeq). These factors included host g...

Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence.

PubMed

Kendler, K S; Gardner, C O

2017-07-01

This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD). Our sample was 2153 members of female-female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves. The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors. Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

You are my teachers.

PubMed

Edlich, Richard F

2005-01-01

Dr. Owen Wangensteen reminded Dr. Edlich that the chief responsibility of a teacher is to create an atmosphere friendly to learning. Dr Wangensteen indicated that the role of professor has been defined as that of teacher, clinician, and investigator. He then indicated that two more responsibilities must be added: (1) sideline cheerleader and (2) regimental water carrier. Above all those enumerated functions, he believed that the most important concern of a professor is to create an atmosphere friendly to learning. He/she must have the willingness to recognize every type of talent and ability and to encourage men/women of promise. He must be the professor of the open door, easily accessible to students, residents, and associates. The major goal of Dr. Edlich's comments, as he receives the Distinguished Medical Alumni Award from The Minneapolis Medical Alumni Association (Minneapolis, Minnesota, USA) is to acknowledge his distinguished colleagues and friends who have served as his teachers during his academic career. They include the following individuals: Theodore J. Edlich, III, President of Total Action Against Poverty; Elizabeth C. Edlic, Cofounder/Chairman and Chief Executive Officer of OneWorldLive; Richard F. Edlich, Jr., President of Edlich Realty; Rachel C. Edlich, Executive Vice President and Cofounder of OneWorldLive; William B. Long, III, MD, President and Medical Director of Trauma Specialists LLP; William P. Magee, MD, Cofounder and Director of Operation Smile; John Barrow, President of Coolibar Incorporated; Mary M. Barrow, Cofounder of Coolibar Incorporated; Kathryne L. Winters, Website Manager and Senior Research Assistant; Lise Borel, DDS, Independent Pharmaceutical/Biotechnical Consultant; Mary Jude Cox, MD, Board Certified Glaucoma Specialist, Teaching Staff at Wills Eye Hospital Glaucoma Service; John Wish, PhD, Member of the Board of The Association of Air Medical Services, Director of the Research Committee; and Dr. Andrew J. Gear, Plastic Surgical Resident, University of Minnesota Medical School.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

Cognitive arithmetic and problem solving: a comparison of children with specific and general mathematics difficulties.

PubMed

Jordan, N C; Montani, T O

1997-01-01

This study examined problem-solving and number-fact skills in two subgroups of third-grade children with mathematics difficulties (MD): MD-specific (n = 12) and MD-general (n = 12). The MD-specific group had difficulties in mathematics but not in reading, and the MD-general group had difficulties in reading as well as in mathematics. A comparison group of nonimpaired children (n = 24) also was included. The findings showed that on both story and number-fact problems, the MD-specific group performed worse than the nonimpaired group in timed conditions but not in untimed conditions. The MD-general group, on the other hand, performed worse than the nonimpaired group, regardless of whether tasks were timed or not. An analysis of children's strategies in untimed conditions showed that both the MD-specific and the MD-general groups relied more on backup strategies than the nonimpaired group. However, children in the MD-specific group executed backup strategies more skillfully than children in the MD-general group, allowing them to achieve parity with children in the nonimpaired group when tasks were not timed. The findings suggest that children with specific MD have circumscribed deficits associated with fact retrieval, whereas children with general MD have more basic delays associated with problem conceptualization and execution of calculation procedures.

Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Takeda, Ryuji; Shiraga, Fumio

2015-01-01

To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran-Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG.

Sleep patterns, sleep disorders and mammographic density in spanish women: The DDM-Spain/Var-DDM study.

PubMed

Pedraza-Flechas, Ana María; Lope, Virginia; Moreo, Pilar; Ascunce, Nieves; Miranda-García, Josefa; Vidal, Carmen; Sánchez-Contador, Carmen; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Llobet, Rafael; Aragonés, Nuria; Salas-Trejo, Dolores; Pollán, Marina; Pérez-Gómez, Beatriz

2017-05-01

We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (e β :1.53;95%CI:1.04-2.26). Copyright © 2017 Elsevier B.V. All rights reserved.

Auditory selective attention in adolescents with major depression: An event-related potential study.

PubMed

Greimel, E; Trinkl, M; Bartling, J; Bakos, S; Grossheinrich, N; Schulte-Körne, G

2015-02-01

Major depression (MD) is associated with deficits in selective attention. Previous studies in adults with MD using event-related potentials (ERPs) reported abnormalities in the neurophysiological correlates of auditory selective attention. However, it is yet unclear whether these findings can be generalized to MD in adolescence. Thus, the aim of the present ERP study was to explore the neural mechanisms of auditory selective attention in adolescents with MD. 24 male and female unmedicated adolescents with MD and 21 control subjects were included in the study. ERPs were collected during an auditory oddball paradigm. Depressive adolescents tended to show a longer N100 latency to target and non-target tones. Moreover, MD subjects showed a prolonged latency of the P200 component to targets. Across groups, longer P200 latency was associated with a decreased tendency of disinhibited behavior as assessed by a behavioral questionnaire. To be able to draw more precise conclusions about differences between the neural bases of selective attention in adolescents vs. adults with MD, future studies should include both age groups and apply the same experimental setting across all subjects. The study provides strong support for abnormalities in the neurophysiolgical bases of selective attention in adolecents with MD at early stages of auditory information processing. Absent group differences in later ERP components reflecting voluntary attentional processes stand in contrast to results reported in adults with MD and may suggest that adolescents with MD possess mechanisms to compensate for abnormalities in the early stages of selective attention. Copyright © 2014 Elsevier B.V. All rights reserved.

Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

PubMed

Parnaudeau, Sébastien; Taylor, Kathleen; Bolkan, Scott S; Ward, Ryan D; Balsam, Peter D; Kellendonk, Christoph

2015-03-01

Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice). While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Using collective variables to drive molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Fiorin, Giacomo; Klein, Michael L.; Hénin, Jérôme

2013-12-01

A software framework is introduced that facilitates the application of biasing algorithms to collective variables of the type commonly employed to drive massively parallel molecular dynamics (MD) simulations. The modular framework that is presented enables one to combine existing collective variables into new ones, and combine any chosen collective variable with available biasing methods. The latter include the classic time-dependent biases referred to as steered MD and targeted MD, the temperature-accelerated MD algorithm, as well as the adaptive free-energy biases called metadynamics and adaptive biasing force. The present modular software is extensible, and portable between commonly used MD simulation engines.

Clinical evaluation of Morgellons disease in a cohort of North American patients

PubMed Central

Fesler, Melissa C.; Middelveen, Marianne J.; Stricker, Raphael B.

2018-01-01

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study. PMID:29774138

Clinical evaluation of Morgellons disease in a cohort of North American patients.

PubMed

Fesler, Melissa C; Middelveen, Marianne J; Stricker, Raphael B

2018-04-23

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi , the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

mdFoam+: Advanced molecular dynamics in OpenFOAM

NASA Astrophysics Data System (ADS)

Longshaw, S. M.; Borg, M. K.; Ramisetti, S. B.; Zhang, J.; Lockerby, D. A.; Emerson, D. R.; Reese, J. M.

2018-03-01

This paper introduces mdFoam+, which is an MPI parallelised molecular dynamics (MD) solver implemented entirely within the OpenFOAM software framework. It is open-source and released under the same GNU General Public License (GPL) as OpenFOAM. The source code is released as a publicly open software repository that includes detailed documentation and tutorial cases. Since mdFoam+ is designed entirely within the OpenFOAM C++ object-oriented framework, it inherits a number of key features. The code is designed for extensibility and flexibility, so it is aimed first and foremost as an MD research tool, in which new models and test cases can be developed and tested rapidly. Implementing mdFoam+ in OpenFOAM also enables easier development of hybrid methods that couple MD with continuum-based solvers. Setting up MD cases follows the standard OpenFOAM format, as mdFoam+ also relies upon the OpenFOAM dictionary-based directory structure. This ensures that useful pre- and post-processing capabilities provided by OpenFOAM remain available even though the fully Lagrangian nature of an MD simulation is not typical of most OpenFOAM applications. Results show that mdFoam+ compares well to another well-known MD code (e.g. LAMMPS) in terms of benchmark problems, although it also has additional functionality that does not exist in other open-source MD codes.

Sex similarities and differences in risk factors for recurrence of major depression.

PubMed

van Loo, Hanna M; Aggen, Steven H; Gardner, Charles O; Kendler, Kenneth S

2017-11-27

Major depression (MD) occurs about twice as often in women as in men, but it is unclear whether sex differences subsist after disease onset. This study aims to elucidate potential sex differences in rates and risk factors for MD recurrence, in order to improve prediction of course of illness and understanding of its underlying mechanisms. We used prospective data from a general population sample (n = 653) that experienced a recent episode of MD. A diverse set of potential risk factors for recurrence of MD was analyzed using Cox models subject to elastic net regularization for males and females separately. Accuracy of the prediction models was tested in same-sex and opposite-sex test data. Additionally, interactions between sex and each of the risk factors were investigated to identify potential sex differences. Recurrence rates and the impact of most risk factors were similar for men and women. For both sexes, prediction models were highly multifactorial including risk factors such as comorbid anxiety, early traumas, and family history. Some subtle sex differences were detected: for men, prediction models included more risk factors concerning characteristics of the depressive episode and family history of MD and generalized anxiety, whereas for women, models included more risk factors concerning early and recent adverse life events and socioeconomic problems. No prominent sex differences in risk factors for recurrence of MD were found, potentially indicating similar disease maintaining mechanisms for both sexes. Course of MD is a multifactorial phenomenon for both males and females.

Using Social Media Data to Identify Potential Candidates for Drug Repurposing: A Feasibility Study.

PubMed

Rastegar-Mojarad, Majid; Liu, Hongfang; Nambisan, Priya

2016-06-16

Drug repurposing (defined as discovering new indications for existing drugs) could play a significant role in drug development, especially considering the declining success rates of developing novel drugs. Typically, new indications for existing medications are identified by accident. However, new technologies and a large number of available resources enable the development of systematic approaches to identify and validate drug-repurposing candidates. Patients today report their experiences with medications on social media and reveal side effects as well as beneficial effects of those medications. Our aim was to assess the feasibility of using patient reviews from social media to identify potential candidates for drug repurposing. We retrieved patient reviews of 180 medications from an online forum, WebMD. Using dictionary-based and machine learning approaches, we identified disease names in the reviews. Several publicly available resources were used to exclude comments containing known indications and adverse drug effects. After manually reviewing some of the remaining comments, we implemented a rule-based system to identify beneficial effects. The dictionary-based system and machine learning system identified 2178 and 6171 disease names respectively in 64,616 patient comments. We provided a list of 10 common patterns that patients used to report any beneficial effects or uses of medication. After manually reviewing the comments tagged by our rule-based system, we identified five potential drug repurposing candidates. To our knowledge, this is the first study to consider using social media data to identify drug-repurposing candidates. We found that even a rule-based system, with a limited number of rules, could identify beneficial effect mentions in patient comments. Our preliminary study shows that social media has the potential to be used in drug repurposing.

33 CFR 165.509 - Security Zone; Severn River and College Creek, Annapolis, MD.

Code of Federal Regulations, 2010 CFR

2010-07-01

... College Creek, Annapolis, MD. 165.509 Section 165.509 Navigation and Navigable Waters COAST GUARD... § 165.509 Security Zone; Severn River and College Creek, Annapolis, MD. (a) Definitions. For purposes of... the Naval Academy waterfront. This security zone includes the waters of College Creek eastward of the...

Marfan syndrome associated aortic disease in neonates and children: a clinical-morphologic review.

PubMed

Ware, Adam L; Miller, Dylan V; Erickson, Lance K; Menon, Shaji C

2016-01-01

Marfan syndrome (MFS) is a multisystem connective tissue disorder that can lead to aortic dilation requiring aortic root replacement. Neonatal MFS (nMFS) is a rare and severe form of MFS compared to classic MFS (cMFS). Aortic root histology in MFS is thought to demonstrate predominantly medial degeneration (MD) of a translamellar mucoid extracellular matrix accumulation (MEMA-T) vs. the intralamellar mucoid extracellular matrix accumulation (MEMA-I) seen in other aortopathies. The objective of this study was to describe the clinical and histopathologic features of nMFS and cMFS patients undergoing aortic root replacement. Children with MFS who underwent aortic root replacement between 2000 and 2012 at a single institution were included. Medical records including clinical details, aortic dimensions (Z scores), and histology including MD type were obtained. Statistics were descriptive with univariate analysis of age at surgery and type of MD. Eleven patients, 3 (27%) with nMFS, were included. Root dilation at time of surgery was greater in nMFS compared to cMFS (Z=12.8 vs. 7.6, P=.005), and nMFS patients were younger at time of surgery (7.3 vs. 18.8 years, P=.002). Histology in the nMFS group demonstrated MEMA-I in one and no MD in two. In the cMFS group, there were three with MEMA-T, four with MEMA-I, and one with both types. In summary, nMFS has earlier root dilation often in the absence of MD. Both forms of MD were present in our cohort, and there was no correlation between age at surgery and type of MD. Copyright © 2016 Elsevier Inc. All rights reserved.

Replica Exchange Gaussian Accelerated Molecular Dynamics: Improved Enhanced Sampling and Free Energy Calculation.

PubMed

Huang, Yu-Ming M; McCammon, J Andrew; Miao, Yinglong

2018-04-10

Through adding a harmonic boost potential to smooth the system potential energy surface, Gaussian accelerated molecular dynamics (GaMD) provides enhanced sampling and free energy calculation of biomolecules without the need of predefined reaction coordinates. This work continues to improve the acceleration power and energy reweighting of the GaMD by combining the GaMD with replica exchange algorithms. Two versions of replica exchange GaMD (rex-GaMD) are presented: force constant rex-GaMD and threshold energy rex-GaMD. During simulations of force constant rex-GaMD, the boost potential can be exchanged between replicas of different harmonic force constants with fixed threshold energy. However, the algorithm of threshold energy rex-GaMD tends to switch the threshold energy between lower and upper bounds for generating different levels of boost potential. Testing simulations on three model systems, including the alanine dipeptide, chignolin, and HIV protease, demonstrate that through continuous exchanges of the boost potential, the rex-GaMD simulations not only enhance the conformational transitions of the systems but also narrow down the distribution width of the applied boost potential for accurate energetic reweighting to recover biomolecular free energy profiles.

Analysis of MD5 authentication in various routing protocols using simulation tools

NASA Astrophysics Data System (ADS)

Dinakaran, M.; Darshan, K. N.; Patel, Harsh

2017-11-01

Authentication being an important paradigm of security and Computer Networks require secure paths to make the flow of the data even more secure through some security protocols. So MD-5(Message Digest 5) helps in providing data integrity to the data being sent through it and authentication to the network devices. This paper gives a brief introduction to the MD-5, simulation of the networks by including MD-5 authentication using various routing protocols like OSPF, EIGRP and RIPv2. GNS3 is being used to simulate the scenarios. Analysis of the MD-5 authentication is done in the later sections of the paper.

Social, societal, and economic burden of mal de debarquement syndrome.

PubMed

Macke, Allison; LePorte, Andrew; Clark, Brian C

2012-07-01

Mal de debarquement syndrome (MdDS) is a disorder of phantom perception of self-motion of unknown cause. The purpose of this work was to describe the quality of life (QOL) of patients with MdDS and to estimate the economic costs associated with this disorder. A modified version of a QOL survey used for another neurological disease (multiple sclerosis; MSQOL-54) was used to assess the impact of MdDS on QOL in 101 patients. The estimated economic costs were based on self-reported direct and indirect costs of individuals living in the United States using Medicare reimbursement payment rates for 2011 in 79 patients. Patients with MdDS reported a poor overall QOL as indicated by a mean composite QOL score of 59.26 ± 1.89 (out of 100). The subcategories having the lowest QOL rating were role limitations due to physical problems (18.32 ± 3.20), energy (34.24 ± 1.47), and emotional problems (36.30 ± 4.00). The overall physical health composite score including balance was 49.40 ± 1.69, and the overall mental health composite score was 52.40 ± 1.83. The cost to obtain a diagnosis was $2,997 ± 337, which included requiring an average of 19 physician visits per patient. The direct cost of MdDS medical care was $826 ± 140 per patient per year, which mainly included diagnostic imaging and physician visits. The indirect costs (i.e., lost wages) were $9,781 ± 2,347 per patient per year. Among 65 patients who were gainfully employed when they acquired MdDS, the indirect costs were $11,888 ± 2,786 per patient per year. Thus, the total annual cost of the disorder ranged from $11,493 ± 2,341 to $13,561 ± 2,778 per patient per year depending on employment status prior to developing MdDS. MdDS negatively and dramatically impacts QOL, and also imposes a substantial economic burden on MdDS patients. These findings underscore the need for further basic and clinical research on MdDS.

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density.

PubMed

Haakensen, Vilde D; Biong, Margarethe; Lingjærde, Ole Christian; Holmen, Marit Muri; Frantzen, Jan Ole; Chen, Ying; Navjord, Dina; Romundstad, Linda; Lüders, Torben; Bukholm, Ida K; Solvang, Hiroko K; Kristensen, Vessela N; Ursin, Giske; Børresen-Dale, Anne-Lise; Helland, Aslaug

2010-01-01

Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer.

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density

PubMed Central

2010-01-01

Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer. PMID:20799965

Scheduling of eccentric lower limb injury prevention exercises during the soccer micro-cycle: Which day of the week?

PubMed

Lovell, R; Whalan, M; Marshall, P W M; Sampson, J A; Siegler, J C; Buchheit, M

2018-05-24

Scheduling eccentric-based injury prevention programs (IPP) during the common 6-day micro-cycle in soccer is challenged by recovery and tapering phases. This study profiled muscle damage, neuromuscular performance, and perceptual responses to a lower limb eccentric-based IPP administered 1 (MD+1) vs 3 days (MD+3) postmatch. A total of 18 semi-professional players were monitored daily during 3 in-season 6-day micro-cycles, including weekly competitive fixtures. Capillary creatine kinase concentration (CK), posterior lower limb isometric peak force (PF), counter-movement jump (CMJ) performance, and muscle soreness were assessed 24 hours prior to match-day (baseline), and every 24 hours up to 120 hours postmatch. The IPP consisted of lunges, single stiff leg dead-lifts, single leg-squats, and Nordic hamstring exercises. Performing the IPP on MD+1 attenuated the decline in CK normally observed following match play (CON: 142%; MD+3: 166%; small differences). When IPP was delivered on MD+3, CK was higher vs CON and MD+1 trials on both MD+4 (MD+3: 260%; CON: 146%; MD+1: 151%; moderate differences) and MD+5 (MD+3: 209%; CON: 125%; MD+1: 127%; small differences). Soreness ratings were not exacerbated when the IPP was delivered on MD+1, but when prescribed on MD+3, hamstring soreness ratings remained higher on MD+4 and MD+5 (small differences). No between-trial differences were observed for PF and CMJ. Administering the IPP in the middle of the micro-cycle (MD+3) increased measures of muscle damage and soreness, which remained elevated on the day prior to the next match (MD+5). Accordingly, IPP should be scheduled early in the micro-cycle, to avoid compromising preparation for the following match. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Opinion of stakeholders on existing curriculum for postgraduate (MD) course in Pharmacology: A survey.

PubMed

Badyal, Dinesh K; Daniel, Sujit R

2016-10-01

To survey the opinion about various curricular components of Doctor of Medicine (MD) pharmacology curriculum in India by stakeholders, including faculty and students. An online survey was done to evaluate the various curricular components of MD pharmacology curriculum being used in India. A total of 393 respondents including faculty, MD students, and other stakeholders completed the survey. The survey was developed using SurveyMonkey platform and link to survey was E-mailed to stakeholders. The results were expressed as percentages. There was a balanced representation of respondents from various designations, teaching experience, regions, and age groups. Most of the respondents (83%) were aware of the MD pharmacology curriculum. However, they reported that it is more inclined to knowledge domain. About half of respondents (53%) said that animal experiments are being used. The most common teaching methods mentioned are seminars (98.5%), journal clubs (95%), and practical exercises by postgraduates (73%), but there is less use of newer methods (25%) in theory and less of clinical pharmacology exercise (39%) in practical classes. The log books are maintained but not assessed regularly. Internal assessment is sparingly used. The MD pharmacology curriculum needs to be made uniform at the national level and updated to include the newer methods in teaching-learning and assessment. There should be sharing of newer methods at a common platform implemented at the national level.

Apple fruit acidity is genetically diversified by natural variations in three hierarchical epistatic genes MdSAUR37, MdPP2CH and MdALMTII.

PubMed

Jia, Dongjie; Shen, Fei; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

2018-05-11

Many efforts have been made to map quantitative trait loci (QTLs) to facilitate practical marker-assisted selection (MAS) in plants. In the present study, we identified four genome-wide major QTLs responsible for apple fruit acidity by MapQTL and BSA-seq analyses using two independent pedigree-based populations. Candidate genes were screened in major QTL regions, and three functional gene markers, including a non-synonymous A/G single nucleotide polymorphism (SNP) in the coding region of MdPP2CH, a 36-bp insertion in the promoter of MdSAUR37, and a previously reported SNP in MdALMTII, were validated to influence the malate content of apple fruits. In addition, MdPP2CH inactivated three vacuolar H + -ATPases (MdVHA-A3, MdVHA-B2 and MdVHA-D2) and one aluminium-activated malate transporter (MdALMTII) via dephosphorylation and negatively influenced fruit malate accumulation. The dephosphotase activity of MdPP2CH was suppressed by MdSAUR37, which implied a higher hierarchy of genetic interaction. Therefore, the MdSAUR37/MdPP2CH/MdALMTII chain cascaded hierarchical epistatic genetic effects to precisely determine apple fruit malate content. An A/G SNP (-1010) on MdMYB44 promoter region from a major QTL (qtl08.1) was closely associated with fruit malate content. The predicted phenotype values (PPVs) were estimated using the tentative genotype values of the gene markers, and the PPVs were significantly correlated with the observed phenotype values. Our findings provide an insight into plant genome-based selection in apples and will aid in conducting research to understand the physiological fundamentals of quantitative genetics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Balloon-assisted enteroscopy for suspected Meckel’s diverticulum and indefinite diagnostic imaging workup

PubMed Central

Gomes, Guilherme Francisco; Bonin, Eduardo Aimore; Noda, Rafael William; Cavazzola, Leandro Totti; Bartholomei, Thiago Ferreira

2016-01-01

Meckel’s diverticulum (MD) is estimated to affect 1%-2% of the general population, and it represents a clinically silent finding of a congenital anomaly in up to 85% of the cases. In adults, MD may cause symptoms, such as overt occult lower gastrointestinal bleeding. The diagnostic imaging workup includes computed tomography scan, magnetic resonance imaging enterography, technetium 99m scintigraphy (99mTc) using either labeled red blood cells or pertechnetate (known as the Meckel’s scan) and angiography. The preoperative detection rate of MD in adults is low, and many patients ultimately undergo exploratory laparoscopy. More recently, however, endoscopic identification of MD has been possible with the use of balloon-assisted enteroscopy via direct luminal access, which also provides visualization of the diverticular ostium. The aim of this study was to review the diagnosis by double-balloon enteroscopy of 4 adults with symptomatic MD but who had negative diagnostic imaging workups. These cases indicate that balloon-assisted enteroscopy is a valuable diagnostic method and should be considered in adult patients who have suspected MD and indefinite findings on diagnostic imaging workup, including negative Meckel’s scan. PMID:27803776

Effects of two-temperature model on cascade evolution in Ni and NiFe

DOE PAGES

Samolyuk, German D.; Xue, Haizhou; Bei, Hongbin; ...

2016-07-05

We perform molecular dynamics simulations of Ni ion cascades in Ni and equiatomic NiFe under the following conditions: (a) classical molecular dynamics (MD) simulations without consideration of electronic energy loss, (b) classical MD simulations with the electronic stopping included, and (c) using the coupled two-temperature MD (2T-MD) model that incorporates both the electronic stopping and the electron-phonon interactions. Our results indicate that the electronic effects are more profound in the higher-energy cascades, and that the 2T-MD model results in a smaller amount of surviving damage and smaller defect clusters, while less damage is produced in NiFe than in Ni.

Volumetrics relate to the development of depression after traumatic brain injury.

PubMed

Maller, Jerome J; Thomson, Richard H S; Pannek, Kerstin; Bailey, Neil; Lewis, Philip M; Fitzgerald, Paul B

2014-09-01

Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

Physician self-disclosure in primary care visits: enough about you, what about me?

PubMed

McDaniel, Susan H; Beckman, Howard B; Morse, Diane S; Silberman, Jordan; Seaburn, David B; Epstein, Ronald M

2007-06-25

The value of physician self-disclosure (MD-SD) in creating successful patient-physician partnerships has not been demonstrated. To describe antecedents, delivery, and effects of MD-SD in primary care visits, we conducted a descriptive study using sequence analysis of transcripts of 113 unannounced, undetected, standardized patient visits to primary care physicians. Our main outcome measures were the number of MD-SDs per visit; number of visits with MD-SDs; word count; antecedents, timing, and effect of MD-SD on subsequent physician and patient communication; content and focus of MD-SD. The MD-SDs included discussion of personal emotions and experiences, families and/or relationships, professional descriptions, and personal experiences with the patient's diagnosis. Seventy-three MD-SDs were identified in 38 (34%) of 113 visits. Ten MD-SDs (14%) were a response to a patient question. Forty-four (60%) followed patient symptoms, family, or feelings; 29 (40%) were unrelated. Only 29 encounters (21%) returned to the patient topic preceding the disclosure. Most MD-SDs (n=62; 85%) were not considered useful to the patient by the research team. Eight MD-SDs (11%) were coded as disruptive. Practicing primary care physicians disclosed information about themselves or their families in 34% of new visits with unannounced, undetected, standardized patients. There was no evidence of positive effect of MD-SDs; some appeared disruptive. Primary care physicians should consider when self-disclosing whether other behaviors such as empathy might accomplish their goals more effectively.

Water consumption footprint and land requirements of large-scale alternative diesel and jet fuel production.

PubMed

Staples, Mark D; Olcay, Hakan; Malina, Robert; Trivedi, Parthsarathi; Pearlson, Matthew N; Strzepek, Kenneth; Paltsev, Sergey V; Wollersheim, Christoph; Barrett, Steven R H

2013-01-01

Middle distillate (MD) transportation fuels, including diesel and jet fuel, make up almost 30% of liquid fuel consumption in the United States. Alternative drop-in MD and biodiesel could potentially reduce dependence on crude oil and the greenhouse gas intensity of transportation. However, the water and land resource requirements of these novel fuel production technologies must be better understood. This analysis quantifies the lifecycle green and blue water consumption footprints of producing: MD from conventional crude oil; Fischer-Tropsch MD from natural gas and coal; fermentation and advanced fermentation MD from biomass; and hydroprocessed esters and fatty acids MD and biodiesel from oilseed crops, throughout the contiguous United States. We find that FT MD and alternative MD derived from rainfed biomass have lifecycle blue water consumption footprints of 1.6 to 20.1 Lwater/LMD, comparable to conventional MD, which ranges between 4.1 and 7.4 Lwater/LMD. Alternative MD derived from irrigated biomass has a lifecycle blue water consumption footprint potentially several orders of magnitude larger, between 2.7 and 22 600 Lwater/LMD. Alternative MD derived from biomass has a lifecycle green water consumption footprint between 1.1 and 19 200 Lwater/LMD. Results are disaggregated to characterize the relationship between geo-spatial location and lifecycle water consumption footprint. We also quantify the trade-offs between blue water consumption footprint and areal MD productivity, which ranges from 490 to 4200 LMD/ha, under assumptions of rainfed and irrigated biomass cultivation. Finally, we show that if biomass cultivation for alternative MD is irrigated, the ratio of the increase in areal MD productivity to the increase in blue water consumption footprint is a function of geo-spatial location and feedstock-to-fuel production pathway.

Visiting EPA Region 3’s Offices

EPA Pesticide Factsheets

Information on visiting EPA Region 3’s offices in Philadelphia, Pa., Annapolis, Md., Fort Meade, Md. and Wheeling, W. Va. including the address, building access, public transportation and driving directions.

Dietary supplements for dysmenorrhoea.

PubMed

Pattanittum, Porjai; Kunyanone, Naowarat; Brown, Julie; Sangkomkamhang, Ussanee S; Barnes, Joanne; Seyfoddin, Vahid; Marjoribanks, Jane

2016-03-22

Dysmenorrhoea refers to painful menstrual cramps and is a common gynaecological complaint. Conventional treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and oral contraceptive pills (OCPs), which both reduce myometrial activity (contractions of the uterus). A suggested alternative approach is dietary supplements. We used the term 'dietary supplement' to include herbs or other botanical, vitamins, minerals, enzymes, and amino acids. We excluded traditional Chinese medicines. To determine the efficacy and safety of dietary supplements for treating dysmenorrhoea. We searched sources including the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, PsycINFO (all from inception to 23 March 2015), trial registries, and the reference lists of relevant articles. We included randomised controlled trials (RCTs) of dietary supplements for moderate or severe primary or secondary dysmenorrhoea. We excluded studies of women with an intrauterine device. Eligible comparators were other dietary supplements, placebo, no treatment, or conventional analgesia. Two review authors independently performed study selection, performed data extraction and assessed the risk of bias in the included trials. The primary outcomes were pain intensity and adverse effects. We used a fixed-effect model to calculate odds ratios (ORs) for dichotomous data, and mean differences (MDs) or standardised mean differences (SMDs) for continuous data, with 95% confidence intervals (CIs). We presented data that were unsuitable for analysis either descriptively or in additional tables. We assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. We included 27 RCTs (3101 women). Most included studies were conducted amongst cohorts of students with primary dysmenorrhoea in their late teens or early twenties. Twenty-two studies were conducted in Iran and the rest were performed in other middle-income countries. Only one study addressed secondary dysmenorrhoea. Interventions included 12 different herbal medicines (German chamomile (Matricaria chamomilla, M recutita, Chamomilla recutita), cinnamon (Cinnamomum zeylanicum, C. verum), Damask rose (Rosa damascena), dill (Anethum graveolens), fennel (Foeniculum vulgare), fenugreek (Trigonella foenum-graecum), ginger (Zingiber officinale), guava (Psidium guajava), rhubarb (Rheum emodi), uzara (Xysmalobium undulatum), valerian (Valeriana officinalis), and zataria (Zataria multiflora)) and five non-herbal supplements (fish oil, melatonin, vitamins B1 and E, and zinc sulphate) in a variety of formulations and doses. Comparators included other supplements, placebo, no treatment, and NSAIDs.We judged all the evidence to be of low or very low quality. The main limitations were imprecision due to very small sample sizes, failure to report study methods, and inconsistency. For most comparisons there was only one included study, and very few studies reported adverse effects. Effectiveness of supplements for primary dysmenorrhoea We have presented pain scores (all on a visual analogue scale (VAS) 0 to 10 point scale) or rates of pain relief, or both, at the first post-treatment follow-up. Supplements versus placebo or no treatmentThere was no evidence of effectiveness for vitamin E (MD 0.00 points, 95% CI -0.34 to 0.34; two RCTs, 135 women).There was no consistent evidence of effectiveness for dill (MD -1.15 points, 95% CI -2.22 to -0.08, one RCT, 46 women), guava (MD 0.59, 95% CI -0.13 to 1.31; one RCT, 151 women); one RCT, 73 women), or fennel (MD -0.34 points, 95% CI -0.74 to 0.06; one RCT, 43 women).There was very limited evidence of effectiveness for fenugreek (MD -1.71 points, 95% CI -2.35 to -1.07; one RCT, 101 women), fish oil (MD 1.11 points, 95% CI 0.45 to 1.77; one RCT, 120 women), fish oil plus vitamin B1 (MD -1.21 points, 95% CI -1.79 to -0.63; one RCT, 120 women), ginger (MD -1.55 points, 95% CI -2.43 to -0.68; three RCTs, 266 women; OR 5.44, 95% CI 1.80 to 16.46; one RCT, 69 women), valerian (MD -0.76 points, 95% CI -1.44 to -0.08; one RCT, 100 women), vitamin B1 alone (MD -2.70 points, 95% CI -3.32 to -2.08; one RCT, 120 women), zataria (OR 6.66, 95% CI 2.66 to 16.72; one RCT, 99 women), and zinc sulphate (MD -0.95 points, 95% CI -1.54 to -0.36; one RCT, 99 women).Data on chamomile and cinnamon versus placebo were unsuitable for analysis. Supplements versus NSAIDSThere was no evidence of any difference between NSAIDs and dill (MD 0.13 points, 95% CI -1.01 to 1.27; one RCT, 47 women), fennel (MD -0.70 points, 95% CI -1.81 to 0.41; one RCT, 59 women), guava (MD 1.19, 95% CI 0.42 to 1.96; one RCT, 155 women), rhubarb (MD -0.20 points, 95% CI -0.44 to 0.04; one RCT, 45 women), or valerian (MD points 0.62 , 95% CI 0.03 to 1.21; one RCT, 99 women),There was no consistent evidence of a difference between Damask rose and NSAIDs (MD -0.15 points, 95% CI -0.55 to 0.25; one RCT, 92 women).There was very limited evidence that chamomile was more effective than NSAIDs (MD -1.42 points, 95% CI -1.69 to -1.15; one RCT, 160 women). Supplements versus other supplementsThere was no evidence of a difference in effectiveness between ginger and zinc sulphate (MD 0.02 points, 95% CI -0.58 to 0.62; one RCT, 101 women). Vitamin B1 may be more effective than fish oil (MD -1.59 points, 95% CI -2.25 to -0.93; one RCT, 120 women). Effectiveness of supplements for secondary dysmenorrhoea There was no strong evidence of benefit for melatonin compared to placebo for dysmenorrhoea secondary to endometriosis (data were unsuitable for analysis). Safety of supplements Only four of the 27 included studies reported adverse effects in both treatment groups. There was no evidence of a difference between the groups but data were too scanty to reach any conclusions about safety. There is no high quality evidence to support the effectiveness of any dietary supplement for dysmenorrhoea, and evidence of safety is lacking. However for several supplements there was some low quality evidence of effectiveness and more research is justified.

Correlates of muscle dysmorphia symptomatology in natural bodybuilders: Distinguishing factors in the pursuit of hyper-muscularity.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Hoon, Matthew; Hackett, Daniel; Prvan, Tania; O'Connor, Helen

2017-09-01

Muscle dysmorphia (MD) is characterized by the pathological pursuit of muscularity and leanness, which includes eating- and exercise-related practices. The aim of this cross-sectional study was to identify correlations of MD symptomatology in natural bodybuilders. An online survey assessing diet, supplementation and training practices, and MD and eating disorder symptoms was completed by male bodybuilders with recent experience competing in a drug-tested competition. Sixty participants (age 29.6±7.1 years) completed the survey. Eating disorder scores (β=.298), rate of pre-competition weight loss (β=.307) and number of competitions (β=-.257) were significant predictors of MD. The association between the EAT-26 and MDDI underscores the salience of disordered eating pathology in presentations of MD. Supporting this, greater rate of pre-competition weight loss, which may reflect disordered eating practices, is also associated with MD symptomatology. The inverse association of competition experience suggests novice bodybuilders may display increased MD symptomatology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling surface-water flow and sediment mobility with the Multi-Dimensional Surface-Water Modeling System (MD_SWMS)

USGS Publications Warehouse

McDonald, Richard; Nelson, Jonathan; Kinzel, Paul; Conaway, Jeffrey S.

2006-01-01

The Multi-Dimensional Surface-Water Modeling System (MD_SWMS) is a Graphical User Interface for surface-water flow and sediment-transport models. The capabilities of MD_SWMS for developing models include: importing raw topography and other ancillary data; building the numerical grid and defining initial and boundary conditions; running simulations; visualizing results; and comparing results with measured data.

Pairing Physician Education With Patient Activation to Improve Shared Decisions in Prostate Cancer Screening: A Cluster Randomized Controlled Trial

PubMed Central

Wilkes, Michael S.; Day, Frank C.; Srinivasan, Malathi; Griffin, Erin; Tancredi, Daniel J.; Rainwater, Julie A.; Kravitz, Richard L.; Bell, Douglas S.; Hoffman, Jerome R.

2013-01-01

BACKGROUND Most expert groups recommend shared decision making for prostate cancer screening. Most primary care physicians, however, routinely order a prostate-specific antigen (PSA) test with little or no discussion about whether they believe the potential benefits justify the risk of harm. We sought to assess whether educating primary care physicians and activating their patients to ask about prostate cancer screening had a synergistic effect on shared decision making, rates and types of discussions about prostate cancer screening, and the physician’s final recommendations. METHODS Our study was a cluster randomized controlled trial among primary care physicians and their patients, comparing usual education (control), with physician education alone (MD-Ed), and with physician education and patient activation (MD-Ed+A). Participants included 120 physicians in 5 group practices, and 712 male patients aged 50 to 75 years. The interventions comprised a Web-based educational program for all intervention physicians and MD-Ed+A patients compared with usual education (brochures from the Centers for Disease Control and Prevention). The primary outcome measure was patients’ reported postvisit shared decision making regarding prostate cancer screening; secondary measures included unannounced standardized patients’ reported shared decision making and the physician’s recommendation for prostate cancer screening. RESULTS Patients’ ratings of shared decision making were moderate and did not differ between groups. MD-Ed+A patients reported that physicians had higher prostate cancer screening discussion rates (MD-Ed+A = 65%, MD-Ed = 41%, control=38%; P <.01). Standardized patients reported that physicians seeing MD-Ed+A patients were more neutral during prostate cancer screening recommendations (MD-Ed+A=50%, MD-Ed=33%, control=15%; P <.05). Of the male patients, 80% had had previous PSA tests. CONCLUSIONS Although activating physicians and patients did not lead to significant changes in all aspects of physician attitudes and behaviors that we studied, interventions that involved physicians did have a large effect on their attitudes toward screening and in the discussions they had with patients, including their being more likely than control physicians to engage in prostate cancer screening discussions and more likely to be neutral in their final recommendations. PMID:23835818

Variations in Patterns of Utilization and Charges for the Care of Neck Pain in North Carolina, 2000 to 2009: A Statewide Claims' Data Analysis.

PubMed

Hurwitz, Eric L; Li, Dongmei; Guillen, Jenni; Schneider, Michael J; Stevans, Joel M; Phillips, Reed B; Phelan, Shawn P; Lewis, Eugene A; Armstrong, Richard C; Vassilaki, Maria

2016-05-01

The purpose of the study was to compare utilization and charges generated by medical doctors (MD), doctors of chiropractic (DC) and physical therapists (PT) by provider patterns of care for the treatment of neck pain in North Carolina. This was an analysis of neck-pain-related closed claim data from the North Carolina State Health Plan for Teachers and State Employees (NCSHP) from 2000 to 2009. Data were extracted from Blue Cross Blue Shield of North Carolina for the NCSHP using ICD-9 diagnostic codes for uncomplicated neck pain (UNP) and complicated neck pain (CNP). Care patterns with single-provider types and no referrals incurred the least average charges for both UNP and CNP. When care did not include referral providers or services, for either UNP or CNP, MD care with PT was generally less expensive than MD care with DC care. However, when care involved referral providers or services, MD and PT care was on average more expensive than MD and DC care for either UNP or CNP. Risk-adjusted charges for patients in the middle quintile of risk (available 2006-2009) were lower for chiropractic patients with or without medical care or referral care to other providers. Chiropractic care alone or DC with MD care incurred appreciably fewer charges for UNP or CNP compared to MD care with or without PT care, when care included referral providers or services. This finding was reversed when care did not include referral providers or services. Risk-adjusted charges for UNP and CNP patients were lower for DC care patterns. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Herbal medicine for adults with asthma: A systematic review.

PubMed

Shergis, Johannah L; Wu, Lei; Zhang, Anthony L; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie C

2016-08-01

Many people with asthma use herbal medicines to help reduce symptoms and improve asthma control. To update the systematic review and meta-analysis of randomised controlled trials of herbal medicine for adult asthma. Nine English and Chinese databases were searched (PubMed, Embase, CINAHL, CENTRAL, AMED, CBM, CNKI, CQVIP, Wanfang). Herbal medicines combined with routine pharmacotherapies compared with the same pharmacotherapies alone or placebo. Cochrane Risk of Bias Tool and GRADE Summary of Findings tables were used to evaluate methodological quality. Twenty-nine (29) studies involving 3,001 participants were included. Herbal interventions used multi-ingredients such as licorice root, crow-dipper, astragali, and angelica. Compared with routine pharmacotherapies alone, herbal medicines as add-on therapy improved lung function (FEV1: MD 7.81%, 95% CI 5.79, 9.83, I(2) = 63%; PEFR: MD 65.14 L/min, 95% CI 58.87, 71.41, I(2) = 21%); asthma control (MD 2.47 points, 95% CI 1.64, 3.29, I(2) = 55%); reduced salbutamol usage (MD -1.14 puffs/day, 95% CI -2.20, -0.09, I(2) = 92%); and reduced acute asthma exacerbations over one year (MD -1.20, 95% CI -1.82, -0.58, one study). Compared with placebo plus pharmacotherapies herbal medicines as add-on therapy improved lung function (FEV1: MD 15.83%, 95% CI 13.54, 18.12 and PEFR: MD 55.20 L/min, 95% CI 33.41, 76.99). Other outcomes were not reported in these placebo studies. Included studies were low to moderate quality. Adverse events were rare. Herbal medicines combined with routine pharmacotherapies improved asthma outcomes greater than pharmacotherapies alone. Included studies did not blind participants therefore more studies that address such weaknesses are warranted.

Quality of life in age-related macular degeneration: a review of the literature

PubMed Central

Mitchell, Jan; Bradley, Clare

2006-01-01

Background The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is reproduced here. Review MD is a chronic, largely untreatable eye condition which leads to loss of central vision needed for tasks such as reading, watching TV, driving, recognising faces. It is the most common cause of blindness in the Western world. Shock of diagnosis, coupled with lack of information and support are a common experience. Incidence of depression is twice that found in the community-dwelling elderly, fuelled by functional decline and loss of leisure activities. Some people feel suicidal. MD threatens independence, especially when comorbidity exacerbates functional limitations. Rehabilitation, including low vision aid (LVA) provision and training, peer support and education, can improve functional and psychological outcomes but many people do not receive services likely to benefit them. Medical treatments, suitable for only a small minority of people with MD, can improve vision but most limit progress of MD, at least for a time, rather than cure. The White Paper considers difficulties associated with inappropriate use of health status measures and misinterpretation of utility values as QoL measures: evidence suggests they have poor validity in MD. Conclusion There is considerable evidence for the major damage done to QoL by MD which is underestimated by health status and utility measures. Medical treatments are limited to a small proportion of people. However, much can be done to improve QoL by early diagnosis of MD with good communication of prognosis and continuing support. Support could include provision of LVAs, peer support, education and effective help in adjusting to MD. It is vital that appropriate measures of visual function and QoL be used in building a sound evidence base for the effectiveness of rehabilitation and treatment. PMID:17184527

Enhanced conformational sampling of nucleic acids by a new Hamiltonian replica exchange molecular dynamics approach.

PubMed

Curuksu, Jeremy; Zacharias, Martin

2009-03-14

Although molecular dynamics (MD) simulations have been applied frequently to study flexible molecules, the sampling of conformational states separated by barriers is limited due to currently possible simulation time scales. Replica-exchange (Rex)MD simulations that allow for exchanges between simulations performed at different temperatures (T-RexMD) can achieve improved conformational sampling. However, in the case of T-RexMD the computational demand grows rapidly with system size. A Hamiltonian RexMD method that specifically enhances coupled dihedral angle transitions has been developed. The method employs added biasing potentials as replica parameters that destabilize available dihedral substates and was applied to study coupled dihedral transitions in nucleic acid molecules. The biasing potentials can be either fixed at the beginning of the simulation or optimized during an equilibration phase. The method was extensively tested and compared to conventional MD simulations and T-RexMD simulations on an adenine dinucleotide system and on a DNA abasic site. The biasing potential RexMD method showed improved sampling of conformational substates compared to conventional MD simulations similar to T-RexMD simulations but at a fraction of the computational demand. It is well suited to study systematically the fine structure and dynamics of large nucleic acids under realistic conditions including explicit solvent and ions and can be easily extended to other types of molecules.

Comparison of mean deviation with AGIS and CIGTS scores in association with structural parameters in glaucomatous eyes.

PubMed

Naka, Maiko; Kanamori, Akiyasu; Tatsumi, Yasuko; Fujioka, Miyuki; Nagai-Kusuhara, Azusa; Nakamura, Makoto; Negi, Akira

2009-01-01

To evaluate which of the 3 clinically used visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. In 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD> or =-6 dB; moderate, -12 dB< or =MD<-6 dB; advanced, MD<-12 dB). Among structure-function relationships in all subjects, the highest correlation determination (R) was MD with RNFLT (=0.298). CIGTS score showed better R than MD or AGIS score with rim area, but these values were not higher than any R with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. No clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.

Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

PubMed

Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

2014-11-01

Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other pharmacologic interventions in a preclinical model of high MD.

Lactobacillus farciminis MD, a newer strain with potential for bacteriocin and antibiotic assay.

PubMed

Halami, P M; Chandrashekar, A; Nand, K

2000-03-01

A native isolate Lactobacillus farciminis MD isolated from fermenting mushroom exhibited a high degree of sensitivity to the majority of the bacteriocins produced by strains of lactobacilli, leuconostoc and pediococci. Also, the efficacy of Lact. farciminis MD as a sensitive strain for antibiotic assay was established against different antibiotics including ampicillin, cefazoline, chloramphenicol and nitrofurantoin at concentrations of 30 microg each, showing an inhibition zone of 30 mm diameter. The high degree of sensitivity towards bacteriocins and antibiotics provide potential for the exploitation of Lact. farciminis MD in establishing very well-defined bacteriocin producers.

Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering.

PubMed

Wall, Michael E; Van Benschoten, Andrew H; Sauter, Nicholas K; Adams, Paul D; Fraser, James S; Terwilliger, Thomas C

2014-12-16

X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculations of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. Decomposition of the MD model into protein and solvent components indicates that protein-solvent interactions contribute substantially to the overall diffuse intensity. We conclude that diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.

Molecular dynamics: deciphering the data.

PubMed

Dauber-Osguthorpe, P; Maunder, C M; Osguthorpe, D J

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerned motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Molecular dynamics: Deciphering the data

NASA Astrophysics Data System (ADS)

Dauber-Osguthorpe, Pnina; Maunder, Colette M.; Osguthorpe, David J.

1996-06-01

The dynamic behaviour of molecules is important in determining their activity. Molecular dynamics (MD) simulations give a detailed description of motion, from small fluctuations to conformational transitions, and can include solvent effects. However, extracting useful information about conformational motion from a trajectory is not trivial. We have used digital signal-processing techniques to characterise the motion in MD simulations, including: calculating the frequency distribution, applying filtering functions, and extraction of vectors defining the characteristic motion for each frequency in an MD simulation. We describe here some typical results obtained for peptides and proteins. The nature of the low-frequency modes of motion, as obtained from MD and normal mode (NM) analysis, of Ace-(Ala)31-Nma and of a proline mutant is discussed. Low-frequency modes extracted from the MD trajectories of Rop protein and phospholipase A2 reveal characteristic motions of secondary structure elements, as well as concerted motions that are of significance to the protein's biological activity. MD simulations are also used frequently as a tool for conformational searches and for investigating protein folding/unfolding. We have developed a novel method that uses time-domain filtering to channel energy into conformational motion and thus enhance conformational transitions. The selectively enhanced molecular dynamics method is tested on the small molecule hexane.

Accelerated molecular dynamics simulations of protein folding.

PubMed

Miao, Yinglong; Feixas, Ferran; Eun, Changsun; McCammon, J Andrew

2015-07-30

Folding of four fast-folding proteins, including chignolin, Trp-cage, villin headpiece and WW domain, was simulated via accelerated molecular dynamics (aMD). In comparison with hundred-of-microsecond timescale conventional molecular dynamics (cMD) simulations performed on the Anton supercomputer, aMD captured complete folding of the four proteins in significantly shorter simulation time. The folded protein conformations were found within 0.2-2.1 Å of the native NMR or X-ray crystal structures. Free energy profiles calculated through improved reweighting of the aMD simulations using cumulant expansion to the second-order are in good agreement with those obtained from cMD simulations. This allows us to identify distinct conformational states (e.g., unfolded and intermediate) other than the native structure and the protein folding energy barriers. Detailed analysis of protein secondary structures and local key residue interactions provided important insights into the protein folding pathways. Furthermore, the selections of force fields and aMD simulation parameters are discussed in detail. Our work shows usefulness and accuracy of aMD in studying protein folding, providing basic references in using aMD in future protein-folding studies. © 2015 Wiley Periodicals, Inc.

12 CFR 516.120 - What information should a comment include?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false What information should a comment include? 516.120 Section 516.120 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY APPLICATION PROCESSING PROCEDURES Comment Procedures § 516.120 What information should a comment include? (a...

Androgens for the anaemia of chronic kidney disease in adults.

PubMed

Yang, Qianchun; Abudou, Minawaer; Xie, Xi Sheng; Wu, Taixiang

2014-10-09

Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial. The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD. We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014. All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion. Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently. We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.

Studies of the TLR4-associated protein MD-2 using yeast-display and mutational analyses

PubMed Central

Mattis, Daiva M.; Chervin, Adam; Ranoa, Diana; Kelley, Stacy; Tapping, Richard; Kranz, David M.

2015-01-01

Bacterial lipopolysaccharide (LPS) activates the innate immune system by forming a complex with myeloid differentiation factor 2 (MD-2) and Toll-like receptor 4 (TLR4), which is present on antigen presenting cells. MD-2 plays an essential role in this activation of the innate immune system as a member of the ternary complex, TLR4:MD-2:LPS. With the goal of further understanding the molecular details of the interaction of MD-2 with LPS and TLR4, and possibly toward engineering dominant negative regulators of the MD-2 protein, here we subjected MD-2 to a mutational analysis using yeast display. The approach included generation of site-directed alanine mutants, and ligand-driven selections of MD-2 mutant libraries. Our findings showed that: 1) proline mutations in the F119-K132 loop that binds LPS were strongly selected for enhanced yeast surface stability, 2) there was a preference for positive-charged side chains (R/K) at residue 120 for LPS binding, and negative-charged side chains (D/E) for TLR4 binding, 3) aromatic residues were strongly preferred at F119 and F121 for LPS binding, and 4) an MD-2 mutant (T84N/D101A/S118A/S120D/K122P) exhibited increased binding to TLR4 but decreased binding to LPS. These studies revealed the impact of specific residues and regions of MD-2 on the binding of LPS and TLR4, and they provide a framework for further directed evolution of the MD-2 protein. PMID:26320630

A Putative Multiple-Demand System in the Macaque Brain.

PubMed

Mitchell, Daniel J; Bell, Andrew H; Buckley, Mark J; Mitchell, Anna S; Sallet, Jerome; Duncan, John

2016-08-17

In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex. Copyright © 2016 Mitchell et al.

Humanized TLR4/MD-2 mice reveal LPS recognition differentially impacts susceptibility to Yersinia pestis and Salmonella enterica.

PubMed

Hajjar, Adeline M; Ernst, Robert K; Fortuno, Edgardo S; Brasfield, Alicia S; Yam, Cathy S; Newlon, Lindsay A; Kollmann, Tobias R; Miller, Samuel I; Wilson, Christopher B

2012-01-01

Although lipopolysaccharide (LPS) stimulation through the Toll-like receptor (TLR)-4/MD-2 receptor complex activates host defense against Gram-negative bacterial pathogens, how species-specific differences in LPS recognition impact host defense remains undefined. Herein, we establish how temperature dependent shifts in the lipid A of Yersinia pestis LPS that differentially impact recognition by mouse versus human TLR4/MD-2 dictate infection susceptibility. When grown at 37°C, Y. pestis LPS is hypo-acylated and less stimulatory to human compared with murine TLR4/MD-2. By contrast, when grown at reduced temperatures, Y. pestis LPS is more acylated, and stimulates cells equally via human and mouse TLR4/MD-2. To investigate how these temperature dependent shifts in LPS impact infection susceptibility, transgenic mice expressing human rather than mouse TLR4/MD-2 were generated. We found the increased susceptibility to Y. pestis for "humanized" TLR4/MD-2 mice directly paralleled blunted inflammatory cytokine production in response to stimulation with purified LPS. By contrast, for other Gram-negative pathogens with highly acylated lipid A including Salmonella enterica or Escherichia coli, infection susceptibility and the response after stimulation with LPS were indistinguishable between mice expressing human or mouse TLR4/MD-2. Thus, Y. pestis exploits temperature-dependent shifts in LPS acylation to selectively evade recognition by human TLR4/MD-2 uncovered with "humanized" TLR4/MD-2 transgenic mice.

Impacts of Mass-dimension and Area-dimension relationships on retrieval ice particle effective radius from radar and lidar measurements

NASA Astrophysics Data System (ADS)

Ham, S. H.; Kato, S.; Rose, F. G.

2016-12-01

In the retrieval of ice clouds from Radar and Lidar Measurements, mass-Dimension (m-D) and Area-Dimension (A-D) relationships are often used to describe nonspherical ice particle shapes. This study analytically investigates how the assumption of m-D and A-D relationships affects retrieval of ice effective radius. We use gamma and lognormal particle distributions and integrate optical parameters over the size distribution. The effective radius is expressed as a function of radar reflectivity factor, visible extinction coefficient, and parameters describing m-D and A-D relationships. The analytic expressions are used for converting effective radius retrieved from one set of m-D and A-D relationships into that with another set of m-D and A-D, including plates, solid columns, bullets, and mixture of different habits. The conversion method can be used for consistent radiative transfer simulation with cloud retrieval algorithms. In addition, when we want to merge cloud effective radii retrieved from different m-D and A-D, the conversion method can be efficiently used to remove undesired biases caused by m-D and A-D assumptions. Furthermore, the sensitivity of the effective radius to m-D and A-D relationships can be quantified by taking the first derivative of the effective radius with respect to parameters expressing the m-D and A-D relationships.

Improving the Efficiency of Free Energy Calculations in the Amber Molecular Dynamics Package.

PubMed

Kaus, Joseph W; Pierce, Levi T; Walker, Ross C; McCammont, J Andrew

2013-09-10

Alchemical transformations are widely used methods to calculate free energies. Amber has traditionally included support for alchemical transformations as part of the sander molecular dynamics (MD) engine. Here we describe the implementation of a more efficient approach to alchemical transformations in the Amber MD package. Specifically we have implemented this new approach within the more computational efficient and scalable pmemd MD engine that is included with the Amber MD package. The majority of the gain in efficiency comes from the improved design of the calculation, which includes better parallel scaling and reduction in the calculation of redundant terms. This new implementation is able to reproduce results from equivalent simulations run with the existing functionality, but at 2.5 times greater computational efficiency. This new implementation is also able to run softcore simulations at the λ end states making direct calculation of free energies more accurate, compared to the extrapolation required in the existing implementation. The updated alchemical transformation functionality will be included in the next major release of Amber (scheduled for release in Q1 2014) and will be available at http://ambermd.org, under the Amber license.

Improving the Efficiency of Free Energy Calculations in the Amber Molecular Dynamics Package

PubMed Central

Pierce, Levi T.; Walker, Ross C.; McCammont, J. Andrew

2013-01-01

Alchemical transformations are widely used methods to calculate free energies. Amber has traditionally included support for alchemical transformations as part of the sander molecular dynamics (MD) engine. Here we describe the implementation of a more efficient approach to alchemical transformations in the Amber MD package. Specifically we have implemented this new approach within the more computational efficient and scalable pmemd MD engine that is included with the Amber MD package. The majority of the gain in efficiency comes from the improved design of the calculation, which includes better parallel scaling and reduction in the calculation of redundant terms. This new implementation is able to reproduce results from equivalent simulations run with the existing functionality, but at 2.5 times greater computational efficiency. This new implementation is also able to run softcore simulations at the λ end states making direct calculation of free energies more accurate, compared to the extrapolation required in the existing implementation. The updated alchemical transformation functionality will be included in the next major release of Amber (scheduled for release in Q1 2014) and will be available at http://ambermd.org, under the Amber license. PMID:24185531

Marginal analysis in assessing factors contributing time to physician in the Emergency Department using operations data.

PubMed

Pathan, Sameer A; Bhutta, Zain A; Moinudheen, Jibin; Jenkins, Dominic; Silva, Ashwin D; Sharma, Yogdutt; Saleh, Warda A; Khudabakhsh, Zeenat; Irfan, Furqan B; Thomas, Stephen H

2016-01-01

Background: Standard Emergency Department (ED) operations goals include minimization of the time interval (tMD) between patients' initial ED presentation and initial physician evaluation. This study assessed factors known (or suspected) to influence tMD with a two-step goal. The first step was generation of a multivariate model identifying parameters associated with prolongation of tMD at a single study center. The second step was the use of a study center-specific multivariate tMD model as a basis for predictive marginal probability analysis; the marginal model allowed for prediction of the degree of ED operations benefit that would be affected with specific ED operations improvements. Methods: The study was conducted using one month (May 2015) of data obtained from an ED administrative database (EDAD) in an urban academic tertiary ED with an annual census of approximately 500,000; during the study month, the ED saw 39,593 cases. The EDAD data were used to generate a multivariate linear regression model assessing the various demographic and operational covariates' effects on the dependent variable tMD. Predictive marginal probability analysis was used to calculate the relative contributions of key covariates as well as demonstrate the likely tMD impact on modifying those covariates with operational improvements. Analyses were conducted with Stata 14MP, with significance defined at p  < 0.05 and confidence intervals (CIs) reported at the 95% level. Results: In an acceptable linear regression model that accounted for just over half of the overall variance in tMD (adjusted r 2 0.51), important contributors to tMD included shift census ( p  = 0.008), shift time of day ( p  = 0.002), and physician coverage n ( p  = 0.004). These strong associations remained even after adjusting for each other and other covariates. Marginal predictive probability analysis was used to predict the overall tMD impact (improvement from 50 to 43 minutes, p  < 0.001) of consistent staffing with 22 physicians. Conclusions: The analysis identified expected variables contributing to tMD with regression demonstrating significance and effect magnitude of alterations in covariates including patient census, shift time of day, and number of physicians. Marginal analysis provided operationally useful demonstration of the need to adjust physician coverage numbers, prompting changes at the study ED. The methods used in this analysis may prove useful in other EDs wishing to analyze operations information with the goal of predicting which interventions may have the most benefit.

Las Palmeras Molecular Dynamics: A flexible and modular molecular dynamics code

NASA Astrophysics Data System (ADS)

Davis, Sergio; Loyola, Claudia; González, Felipe; Peralta, Joaquín

2010-12-01

Las Palmeras Molecular Dynamics (LPMD) is a highly modular and extensible molecular dynamics (MD) code using interatomic potential functions. LPMD is able to perform equilibrium MD simulations of bulk crystalline solids, amorphous solids and liquids, as well as non-equilibrium MD (NEMD) simulations such as shock wave propagation, projectile impacts, cluster collisions, shearing, deformation under load, heat conduction, heterogeneous melting, among others, which involve unusual MD features like non-moving atoms and walls, unstoppable atoms with constant-velocity, and external forces like electric fields. LPMD is written in C++ as a compromise between efficiency and clarity of design, and its architecture is based on separate components or plug-ins, implemented as modules which are loaded on demand at runtime. The advantage of this architecture is the ability to completely link together the desired components involved in the simulation in different ways at runtime, using a user-friendly control file language which describes the simulation work-flow. As an added bonus, the plug-in API (Application Programming Interface) makes it possible to use the LPMD components to analyze data coming from other simulation packages, convert between input file formats, apply different transformations to saved MD atomic trajectories, and visualize dynamical processes either in real-time or as a post-processing step. Individual components, such as a new potential function, a new integrator, a new file format, new properties to calculate, new real-time visualizers, and even a new algorithm for handling neighbor lists can be easily coded, compiled and tested within LPMD by virtue of its object-oriented API, without the need to modify the rest of the code. LPMD includes already several pair potential functions such as Lennard-Jones, Morse, Buckingham, MCY and the harmonic potential, as well as embedded-atom model (EAM) functions such as the Sutton-Chen and Gupta potentials. Integrators to choose include Euler (if only for demonstration purposes), Verlet and Velocity Verlet, Leapfrog and Beeman, among others. Electrostatic forces are treated as another potential function, by default using the plug-in implementing the Ewald summation method. Program summaryProgram title: LPMD Catalogue identifier: AEHG_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEHG_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License version 3 No. of lines in distributed program, including test data, etc.: 509 490 No. of bytes in distributed program, including test data, etc.: 6 814 754 Distribution format: tar.gz Programming language: C++ Computer: 32-bit and 64-bit workstation Operating system: UNIX RAM: Minimum 1024 bytes Classification: 7.7 External routines: zlib, OpenGL Nature of problem: Study of Statistical Mechanics and Thermodynamics of condensed matter systems, as well as kinetics of non-equilibrium processes in the same systems. Solution method: Equilibrium and non-equilibrium molecular dynamics method, Monte Carlo methods. Restrictions: Rigid molecules are not supported. Polarizable atoms and chemical bonds (proteins) either. Unusual features: The program is able to change the temperature of the simulation cell, the pressure, cut regions of the cell, color the atoms by properties, even during the simulation. It is also possible to fix the positions and/or velocity of groups of atoms. Visualization of atoms and some physical properties during the simulation. Additional comments: The program does not only perform molecular dynamics and Monte Carlo simulations, it is also able to filter and manipulate atomic configurations, read and write different file formats, convert between them, evaluate different structural and dynamical properties. Running time: 50 seconds on a 1000-step simulation of 4000 argon atoms, running on a single 2.67 GHz Intel processor.

Trapped in a Daydream: Daily Elevations in Maladaptive Daydreaming Are Associated With Daily Psychopathological Symptoms.

PubMed

Soffer-Dudek, Nirit; Somer, Eli

2018-01-01

Background: Maladaptive Daydreaming (MD) characterizes individuals who engage in vivid, fanciful daydreaming for hours on end, neglecting real-life relationships and responsibilities, resulting in clinical distress and functional impairment. Sufferers have embraced the term MD in cyber-communities devoted to this problem because it seemed to uniquely fit their experience and since existing diagnostic labels and their therapies seemed inadequate. However, scientific research in the field has been scarce, relying on cross-sectional or case study designs. Existing knowledge on MD suggests the involvement of dissociative and obsessive-compulsive symptoms, as well as positive reinforcement comparable to processes in addiction disorders. The present study aimed to rigorously explore factors that accompany MD employing a longitudinal daily-diary design, hypothesizing that temporal increases in MD will associate concurrently with, and will temporally precede, other symptoms and emotional changes. In addition, we aimed to explore which symptoms may act as precursors to increases in MD, in order to identify possible mechanisms bringing about daydreaming in these individuals. Methods: In a sample of 77 self-diagnosed individuals with MD we assessed relevant daily symptoms for 14 days, including MD, depression, general anxiety, social anxiety, obsessive-compulsive symptoms, and dissociation, as well as positive and negative emotion. Results: Increases in MD were strongly related to concurrent increases in all other symptoms and negative emotion, and to decreased positive emotion. Obsessive-compulsive symptoms, dissociation, and negative emotion also temporally followed MD. Obsessive-compulsive symptoms were the only consistent temporal antecedent of MD. Conclusions: MD and obsessive-compulsive symptoms coincided in what seems to be a vicious cycle; understanding possible shared mechanisms between these symptoms may inform our understanding of the etiology of MD. For example, Serotonin levels may possibly be involved in the development or maintenance of this condition. The findings may also provide clues as to potentially beneficial interventions for treating MD. For example, perhaps utilizing response prevention techniques may be useful for curbing or intercepting unwanted daydreaming. Future studies on MD should address its compulsory nature.

Apple fruit copper amine oxidase isoforms: peroxisomal MdAO1 prefers diamines as substrates, whereas extracellular MdAO2 exclusively utilizes monoamines.

PubMed

Zarei, Adel; Trobacher, Christopher P; Cooke, Alison R; Meyers, Ashley J; Hall, J Christopher; Shelp, Barry J

2015-01-01

4-Aminobutyrate (GABA) accumulates in apple fruit during controlled atmosphere storage. A potential source of GABA is the polyamine putrescine, which can be oxidized via copper-containing amine oxidase (CuAO), resulting in the production 4-aminobutanal/Δ(1)-pyrroline, with the consumption of O2 and release of H2O2 and ammonia. Five putative CuAO genes (MdAO genes) were cloned from apple (Malus domestica Borkh. cv. Empire) fruit, and the deduced amino acid sequences found to contain the active sites typically conserved in CuAOs. Genes encoding two of these enzymes, MdAO1 and MdAO2, were highly expressed in apple fruit and selected for further analysis. Amino acid sequence analysis predicted the presence of a C-terminal peroxisomal targeting signal 1 tripeptide in MdAO1 and an N-terminal signal peptide and N-glycosylation site in MdAO2. Transient expression of green fluorescent fusion proteins in Arabidopsis protoplasts or onion epidermal cells revealed a peroxisomal localization for MdAO1 and an extracellular localization for MdAO2. The enzymatic activities of purified recombinant MdAO1 and MdAO2 were measured continuously as H2O2 production using a coupled reaction. MdAO1 did not use monoamines or polyamines and displayed high catalytic efficiency for 1,3-diaminopropane, putrescine and cadaverine, whereas MdAO2 exclusively utilized aliphatic and aromatic monoamines, including 2-phenylethylamine and tyramine. Together, these results indicate that MdAO1 may contribute to GABA production via putrescine oxidation in the peroxisome of apple fruit under controlled atmosphere conditions. MdAO2 seems to be involved in deamination of 2-phenylethylamine, which is a step in the biosynthesis of 2-phenylethanol, a contributor to fruit flavor and flower fragrance. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Assessing the allelotypic effect of two aminocyclopropane carboxylic acid synthase-encoding genes MdACS1 and MdACS3a on fruit ethylene production and softening in Malus

PubMed Central

Dougherty, Laura; Zhu, Yuandi; Xu, Kenong

2016-01-01

Phytohormone ethylene largely determines apple fruit shelf life and storability. Previous studies demonstrated that MdACS1 and MdACS3a, which encode 1-aminocyclopropane-1-carboxylic acid synthases (ACS), are crucial in apple fruit ethylene production. MdACS1 is well-known to be intimately involved in the climacteric ethylene burst in fruit ripening, while MdACS3a has been regarded a main regulator for ethylene production transition from system 1 (during fruit development) to system 2 (during fruit ripening). However, MdACS3a was also shown to have limited roles in initiating the ripening process lately. To better assess their roles, fruit ethylene production and softening were evaluated at five time points during a 20-day post-harvest period in 97 Malus accessions and in 34 progeny from 2 controlled crosses. Allelotyping was accomplished using an existing marker (ACS1) for MdACS1 and two markers (CAPS866 and CAPS870) developed here to specifically detect the two null alleles (ACS3a-G289V and Mdacs3a) of MdACS3a. In total, 952 Malus accessions were allelotyped with the three markers. The major findings included: The effect of MdACS1 was significant on fruit ethylene production and softening while that of MdACS3a was less detectable; allele MdACS1–2 was significantly associated with low ethylene and slow softening; under the same background of the MdACS1 allelotypes, null allele Mdacs3a (not ACS3a-G289V) could confer a significant delay of ethylene peak; alleles MdACS1–2 and Mdacs3a (excluding ACS3a-G289V) were highly enriched in M. domestica and M. hybrid when compared with those in M. sieversii. These findings are of practical implications in developing apples of low and delayed ethylene profiles by utilizing the beneficial alleles MdACS1-2 and Mdacs3a. PMID:27231553

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

PubMed Central

Rossignol, D A; Frye, R E

2012-01-01

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD. PMID:21263444

The Hugoniot adiabat of crystalline copper based on molecular dynamics simulation and semiempirical equation of state

NASA Astrophysics Data System (ADS)

Gubin, S. A.; Maklashova, I. V.; Mel'nikov, I. N.

2018-01-01

The molecular dynamics (MD) method was used for prediction of properties of copper under shock-wave compression and clarification of the melting region of crystal copper. The embedded atom potential was used for the interatomic interaction. Parameters of Hugonoit adiabats of solid and liquid phases of copper calculated by the semiempirical Grüneisen equation of state are consistent with the results of MD simulations and experimental data. MD simulation allows to visualize the structure of cooper on the atomistic level. The analysis of the radial distribution function and the standard deviation by MD modeling allows to predict the melting area behind the shock wave front. These MD simulation data are required to verify the wide-range equation of state of metals. The melting parameters of copper based on MD simulations and semiempirical equations of state are consistent with experimental and theoretical data, including the region of the melting point of copper.

Cost analysis of mandibular distraction versus tracheostomy in neonates with Pierre Robin sequence.

PubMed

Runyan, Christopher M; Uribe-Rivera, Armando; Karlea, Audrey; Meinzen-Derr, Jareen; Rothchild, Dawn; Saal, Howard; Hopkin, Robert J; Gordon, Christopher B

2014-11-01

To evaluate costs associated with surgical treatment for neonates with Pierre Robin sequence (PRS). Retrospective cohort study. Cincinnati Children's Hospital Medical Center. With Institutional Review Board approval, we retrospectively studied neonates with PRS treated from 2001 to 2009 with either tracheostomy (Trach), mandibular distraction (MD), or Trach with subsequent MD (Trach+MD). Actual charges over a 3-year period associated with operative costs, hospital stay, imaging and sleep studies, clinic visits, and related emergency room visits were collected. Home tracheostomy care charges were estimated individually for each patient. Charges were compared using regression and appropriate statistical analyses. Forty-seven neonates were included in the study (MD, n = 26; Trach, n = 12; Trach+MD, n = 9). Trach group patients had 2.6-fold higher charges than the MD group despite no difference in length of hospital stay. This difference increased to 7.3-fold when including home trach care-related costs. Trach+MD group patients had longer hospital lengths of stay and higher operation room (OR) fees, but no increased total charges compared with the Trach only group. For patients with severe PRS, mandibular distraction provides significant cost savings over tracheostomy ($300,000 per patient over 3 years). Increased costs with tracheostomy come from greater hospital-related charges, more frequent airway procedures, a higher incidence of gastrostomy tube feeds, and home trach care costs. A careful examination of long-term outcomes will be critical as mandibular distraction continues to gain acceptance for treatment of PRS. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.

DEFINING THE RELEVANT OUTCOME MEASURES IN MEDICAL DEVICE ASSESSMENTS: AN ANALYSIS OF THE DEFINITION PROCESS IN HEALTH TECHNOLOGY ASSESSMENT.

PubMed

Jacobs, Esther; Antoine, Sunya-Lee; Prediger, Barbara; Neugebauer, Edmund; Eikermann, Michaela

2017-01-01

Defining relevant outcome measures for clinical trials on medical devices (MD) is complex, as there is a large variety of potentially relevant outcomes. The chosen outcomes vary widely across clinical trials making the assessment in evidence syntheses very challenging. The objective is to provide an overview on the current common procedures of health technology assessment (HTA) institutions in defining outcome measures in MD trials. In 2012-14, the Web pages of 126 institutions involved in HTA were searched for methodological manuals written in English or German that describe methods for the predefinition process of outcome measures. Additionally, the institutions were contacted by email. Relevant information was extracted. All process steps were performed independently by two reviewers. Twenty-four manuals and ten responses from the email request were included in the analysis. Overall, 88.5 percent of the institutions describe the type of outcomes that should be considered in detail and 84.6 percent agree that the main focus should be on patient relevant outcomes. Specifically related to MD, information could be obtained in 26 percent of the included manuals and email responses. Eleven percent of the institutions report a particular consideration of MD related outcomes. This detailed analysis on common procedures of HTA institutions in the context of defining relevant outcome measures for the assessment of MD shows that standardized procedures for MD from the perspective of HTA institutions are not widespread. This leads to the question if a homogenous approach should be implemented in the field of HTA on MD.

Management of mal de debarquement syndrome as vestibular migraines.

PubMed

Ghavami, Yaser; Haidar, Yarah M; Ziai, Kasra N; Moshtaghi, Omid; Bhatt, Jay; Lin, Harrison W; Djalilian, Hamid R

2017-07-01

Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. Management is typically supportive (e.g. physical therapy), and symptoms that persist beyond 6 months have been described as unlikely to remit. This study was conducted to evaluate the response of patients with MdDS to management with migraine prophylaxis, including lifestyle changes and medical therapy. Prospective review. Ambulatory setting at a tertiary care medical center. Clinical history, detailed questionnaires, and audiograms were used to diagnose patients with MdDS. Those patients with the diagnosis of the MdDS were placed on our institutional vestibular migraine management protocol. Treatment response was assessed with a quality-of-life (QOL) survey and visual analog scale. Fifteen patients were diagnosed with MdDS, with a predominance of females (73%) and a mean age of 50 ± 13 years. Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof. In comparison, a retrospective control group of 17 patients demonstrated a lower rate of improvement when treated with vestibular rehabilitation and physical therapy. Management of MdDS as vestibular migraine can improve patients' symptoms and increase the QOL. Nearly all the patients suffering from MdDS had a personal or family history of migraine headaches or had signs or symptoms suggestive of atypical migraine. 4 Laryngoscope, 127:1670-1675, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Theoretical Prediction of Vibrational Circular Dichroism Spectra

DTIC Science & Technology

1990-01-01

Chabalowski U.S. ARMY BALLISTIC RESEARCH LABORATORY January 1990 DTIC ELECTESMAR 6U99 CHEMICAL COMMAN4D Aberden Proving Ground . MeMand 21010-5423 IDWPM...TASK [WORK UNIT ELEMENT NO. NO.11 46 2 6 2 2 NO. A5531 ACCESSION NO. Aberdeen Proving Ground , MD 21010-5423 IC4648061 D020 1 11. TITLE (Include...Engineering Center ATITN: SDCCR-RSP-C Aberdeen Proving Ground , MD 21010-5423 U.S. Army Ballistic Research Laboratory Aberdeen Proving Ground , MD

Mathematical learning disorder in school-age children with attention-deficit hyperactivity disorder.

PubMed

Capano, Lucia; Minden, Debbie; Chen, Shirley X; Schacher, Russell J; Ickowicz, Abel

2008-06-01

To explore the prevalence of mathematics disorder (MD) relative to reading disorders (RD) in school-age children with attention-deficit hyperactivity disorder (ADHD) and examine the effects of age, sex, cooccurring conduct disorder (CD), and ADHD subtype on this comorbidity. Participants were school-age children (n = 476) with confirmed DSM-IV diagnosis of ADHD. The assessment included semistructured parent and teacher interviews and standardized measures of intelligence, academic attainment, and language abilities. Based on the presence or absence of concurrent learning disorders, we compared the emerging 4 groups: ADHD-only, ADHD + MD, ADHD + RD, and ADHD + MD + RD. Overall prevalence of comorbid ADHD + MD was 18.1%. Age, sex, ADHD subtypes, or comorbid CD did not affect the frequency of MD. Children with concurrent ADHD and either MD or RD attained lower IQ, language, and academic scores than those with ADHD alone. Children with ADHD + MD + RD were more seriously impaired and demonstrated distinct deficits in receptive and expressive language. MDs are relatively common in school-age children with ADHD and are frequently associated with RDs. Children with ADHD + MD + RD are more severely impaired. These deficits simply cannot be explained as consequences of ADHD and might have unique biological underpinnings, with implications for diagnostic classification and therapeutic interventions.

Cognitive Risk Factors for Specific Learning Disorder: Processing Speed, Temporal Processing, and Working Memory.

PubMed

Moll, Kristina; Göbel, Silke M; Gooch, Debbie; Landerl, Karin; Snowling, Margaret J

2016-01-01

High comorbidity rates between reading disorder (RD) and mathematics disorder (MD) indicate that, although the cognitive core deficits underlying these disorders are distinct, additional domain-general risk factors might be shared between the disorders. Three domain-general cognitive abilities were investigated in children with RD and MD: processing speed, temporal processing, and working memory. Since attention problems frequently co-occur with learning disorders, the study examined whether these three factors, which are known to be associated with attention problems, account for the comorbidity between these disorders. The sample comprised 99 primary school children in four groups: children with RD, children with MD, children with both disorders (RD+MD), and typically developing children (TD controls). Measures of processing speed, temporal processing, and memory were analyzed in a series of ANCOVAs including attention ratings as covariate. All three risk factors were associated with poor attention. After controlling for attention, associations with RD and MD differed: Although deficits in verbal memory were associated with both RD and MD, reduced processing speed was related to RD, but not MD; and the association with RD was restricted to processing speed for familiar nameable symbols. In contrast, impairments in temporal processing and visuospatial memory were associated with MD, but not RD. © Hammill Institute on Disabilities 2014.

Using molecular simulation to explore the nanoscale dynamics of the plant kinome.

PubMed

Moffett, Alexander S; Shukla, Diwakar

2018-03-09

Eukaryotic protein kinases (PKs) are a large family of proteins critical for cellular response to external signals, acting as molecular switches. PKs propagate biochemical signals by catalyzing phosphorylation of other proteins, including other PKs, which can undergo conformational changes upon phosphorylation and catalyze further phosphorylations. Although PKs have been studied thoroughly across the domains of life, the structures of these proteins are sparsely understood in numerous groups of organisms, including plants. In addition to efforts towards determining crystal structures of PKs, research on human PKs has incorporated molecular dynamics (MD) simulations to study the conformational dynamics underlying the switching of PK function. This approach of experimental structural biology coupled with computational biophysics has led to improved understanding of how PKs become catalytically active and why mutations cause pathological PK behavior, at spatial and temporal resolutions inaccessible to current experimental methods alone. In this review, we argue for the value of applying MD simulation to plant PKs. We review the basics of MD simulation methodology, the successes achieved through MD simulation in animal PKs, and current work on plant PKs using MD simulation. We conclude with a discussion of the future of MD simulations and plant PKs, arguing for the importance of molecular simulation in the future of plant PK research. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering

DOE PAGES

Wall, Michael E.; Van Benschoten, Andrew H.; Sauter, Nicholas K.; ...

2014-12-01

X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculationsmore » of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. The decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. In conclusion, diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.« less

Cummins MD & HD Accessory Hybridization CRADA -Annual Report FY15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deter, Dean D.

2015-10-01

There are many areas of MD and HD vehicles that can be improved by new technologies and optimized control strategies. Component optimization and idle reduction need to be addressed, this is best done by a two part approach that includes selecting the best component technology, and/or architecture, and optimized controls that are vehicle focused. While this is a common focus in the light duty industry it has been gaining momentum in the MD and HD market as the market gets more competitive and the regulations become more stringent. When looking into systems optimization and idle reduction technologies, affected vehicle systemsmore » must first be considered, and if possible included in the new architecture to get the most benefit out of these new capabilities. Typically, when looking into idle reduction or component optimization for MD/HD, the vehicle s accessories become a prime candidate for electrification or hybridization. While this has already been studied on light duty vehicles (especially on hybrids and electric vehicles) it has not made any head way or market penetration in most MD and HD applications. If hybrids and electric MD and HD vehicles begin to break into the market this would be a necessary step into the ability to make those vehicles successful by allowing for independent, optimized operation separate from the engine.« less

Conformational dynamics of a crystalline protein from microsecond-scale molecular dynamics simulations and diffuse X-ray scattering

PubMed Central

Wall, Michael E.; Van Benschoten, Andrew H.; Sauter, Nicholas K.; Adams, Paul D.; Fraser, James S.; Terwilliger, Thomas C.

2014-01-01

X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculations of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. Decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. We conclude that diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions. PMID:25453071

Morgellons disease: a filamentous borrelial dermatitis.

PubMed

Middelveen, Marianne J; Stricker, Raphael B

2016-01-01

Morgellons disease (MD) is a dermopathy characterized by multicolored filaments that lie under, are embedded in, or project from skin. Although MD was initially considered to be a delusional disorder, recent studies have demonstrated that the dermopathy is associated with tickborne infection, that the filaments are composed of keratin and collagen, and that they result from proliferation of keratinocytes and fibroblasts in epithelial tissue. Culture, histopathological and molecular evidence of spirochetal infection associated with MD has been presented in several published studies using a variety of techniques. Spirochetes genetically identified as Borrelia burgdorferi sensu stricto predominate as the infective agent in most of the Morgellons skin specimens studied so far. Other species of Borrelia including Borrelia garinii , Borrelia miyamotoi , and Borrelia hermsii have also been detected in skin specimens taken from MD patients. The optimal treatment for MD remains to be determined.

Morgellons disease: a filamentous borrelial dermatitis

PubMed Central

Middelveen, Marianne J; Stricker, Raphael B

2016-01-01

Morgellons disease (MD) is a dermopathy characterized by multicolored filaments that lie under, are embedded in, or project from skin. Although MD was initially considered to be a delusional disorder, recent studies have demonstrated that the dermopathy is associated with tickborne infection, that the filaments are composed of keratin and collagen, and that they result from proliferation of keratinocytes and fibroblasts in epithelial tissue. Culture, histopathological and molecular evidence of spirochetal infection associated with MD has been presented in several published studies using a variety of techniques. Spirochetes genetically identified as Borrelia burgdorferi sensu stricto predominate as the infective agent in most of the Morgellons skin specimens studied so far. Other species of Borrelia including Borrelia garinii, Borrelia miyamotoi, and Borrelia hermsii have also been detected in skin specimens taken from MD patients. The optimal treatment for MD remains to be determined. PMID:27789971

MaMiCo: Transient multi-instance molecular-continuum flow simulation on supercomputers

NASA Astrophysics Data System (ADS)

Neumann, Philipp; Bian, Xin

2017-11-01

We present extensions of the macro-micro-coupling tool MaMiCo, which was designed to couple continuum fluid dynamics solvers with discrete particle dynamics. To enable local extraction of smooth flow field quantities especially on rather short time scales, sampling over an ensemble of molecular dynamics simulations is introduced. We provide details on these extensions including the transient coupling algorithm, open boundary forcing, and multi-instance sampling. Furthermore, we validate the coupling in Couette flow using different particle simulation software packages and particle models, i.e. molecular dynamics and dissipative particle dynamics. Finally, we demonstrate the parallel scalability of the molecular-continuum simulations by using up to 65 536 compute cores of the supercomputer Shaheen II located at KAUST. Program Files doi:http://dx.doi.org/10.17632/w7rgdrhb85.1 Licensing provisions: BSD 3-clause Programming language: C, C++ External routines/libraries: For compiling: SCons, MPI (optional) Subprograms used: ESPResSo, LAMMPS, ls1 mardyn, waLBerla For installation procedures of the MaMiCo interfaces, see the README files in the respective code directories located in coupling/interface/impl. Journal reference of previous version: P. Neumann, H. Flohr, R. Arora, P. Jarmatz, N. Tchipev, H.-J. Bungartz. MaMiCo: Software design for parallel molecular-continuum flow simulations, Computer Physics Communications 200: 324-335, 2016 Does the new version supersede the previous version?: Yes. The functionality of the previous version is completely retained in the new version. Nature of problem: Coupled molecular-continuum simulation for multi-resolution fluid dynamics: parts of the domain are resolved by molecular dynamics or another particle-based solver whereas large parts are covered by a mesh-based CFD solver, e.g. a lattice Boltzmann automaton. Solution method: We couple existing MD and CFD solvers via MaMiCo (macro-micro coupling tool). Data exchange and coupling algorithmics are abstracted and incorporated in MaMiCo. Once an algorithm is set up in MaMiCo, it can be used and extended, even if other solvers are used (as soon as the respective interfaces are implemented/available). Reasons for the new version: We have incorporated a new algorithm to simulate transient molecular-continuum systems and to automatically sample data over multiple MD runs that can be executed simultaneously (on, e.g., a compute cluster). MaMiCo has further been extended by an interface to incorporate boundary forcing to account for open molecular dynamics boundaries. Besides support for coupling with various MD and CFD frameworks, the new version contains a test case that allows to run molecular-continuum Couette flow simulations out-of-the-box. No external tools or simulation codes are required anymore. However, the user is free to switch from the included MD simulation package to LAMMPS. For details on how to run the transient Couette problem, see the file README in the folder coupling/tests, Remark on MaMiCo V1.1. Summary of revisions: Open boundary forcing; Multi-instance MD sampling; support for transient molecular-continuum systems Restrictions: Currently, only single-centered systems are supported. For access to the LAMMPS-based implementation of DPD boundary forcing, please contact Xin Bian, xin.bian@tum.de. Additional comments: Please see file license_mamico.txt for further details regarding distribution and advertising of this software.

Identification of two novel mammographic density loci at 6Q25.1.

PubMed

Brand, Judith S; Li, Jingmei; Humphreys, Keith; Karlsson, Robert; Eriksson, Mikael; Ivansson, Emma; Hall, Per; Czene, Kamila

2015-06-03

Mammographic density (MD) is a strong heritable and intermediate phenotype for breast cancer, but much of its genetic variation remains unexplained. We performed a large-scale genetic association study including 8,419 women of European ancestry to identify MD loci. Participants of three Swedish studies were genotyped on a custom Illumina iSelect genotyping array and percent and absolute mammographic density were ascertained using semiautomated and fully automated methods from film and digital mammograms. Linear regression analysis was used to test for SNP-MD associations, adjusting for age, body mass index, menopausal status and six principal components. Meta-analyses were performed by combining P values taking sample size, study-specific inflation factor and direction of effect into account. Genome-wide significant associations were observed for two previously identified loci: ZNF365 (rs10995194, P = 2.3 × 10(-8) for percent MD and P = 8.7 × 10(-9) for absolute MD) and AREG (rs10034692, P = 6.7 × 10(-9) for absolute MD). In addition, we found evidence of association for two variants at 6q25.1, both of which are known breast cancer susceptibility loci: rs9485370 in the TAB2 gene (P = 4.8 × 10(-9) for percent MD and P = 2.5 × 10(-8) for absolute MD) and rs60705924 in the CCDC170/ESR1 region (P = 2.2 × 10(-8) for absolute MD). Both regions have been implicated in estrogen receptor signaling with TAB2 being a potential regulator of tamoxifen response. We identified two novel MD loci at 6q25.1. These findings underscore the importance of 6q25.1 as a susceptibility region and provide more insight into the mechanisms through which MD influences breast cancer risk.

In silico analysis of the polygalacturonase inhibiting protein 1 from apple, Malus domestica.

PubMed

Matsaunyane, Lerato Bt; Oelofse, Dean; Dubery, Ian A

2015-03-11

The Malus domestica polygalacturonase inhibiting protein 1 (MdPGIP1) gene, encoding the M. domestica polygalacturonase inhibiting protein 1 (MdPGIP1), was isolated from the Granny Smith apple cultivar (GenBank accession no. DQ185063). The gene was used to transform tobacco and potato for enhanced resistance against fungal diseases. Analysis of the MdPGIP1 nucleotide sequence revealed that the gene comprises 993 nucleotides that encode a 330 amino acid polypeptide. In silico characterization of the MdPGIP1 polypeptide revealed domains typical of PGIP proteins, which include a 24 amino acid putative signal peptide, a potential cleavage site [Alanine-Leucine-Serine (ALS)] for the signal peptide, a 238 amino acid leucine-rich repeat (LRR) domain, a 46 amino acid N-terminal domain and a 22 amino acid C-terminal domain. The hydropathic evaluation of MdPGIP1 indicated a repetitive hydrophobic motif in the LRR domain and a hydrophilic surface area consistent with a globular protein. The typical consensus glycosylation sequence of Asn-X-Ser/Thr was identified in MdPGIP1, indicating potential N-linked glycosylation of MdPGIP1. The molecular mass of non-glycosylated MdPGIP1 was calculated as 36.615 kDa and the theoretical isoelectric point as 6.98. Furthermore, the secondary and tertiary structure of MdPGIP1 was modelled, and revealed that MdPGIP1 is a curved and elongated molecule that contains sheet B1, sheet B2 and 310-helices on its LRR domain. The overall properties of the MdPGIP1 protein is similar to that of the prototypical Phaseolus vulgaris PGIP 2 (PvPGIP2), and the detected differences supported its use in biotechnological applications as an inhibitor of targeted fungal polygalacturonases (PGs).

Past major depression and smoking cessation outcome: a systematic review and meta-analysis update

PubMed Central

Hitsman, Brian; Papandonatos, George D.; McChargue, Dennis E.; DeMott, Andrew; Herrera, María José; Spring, Bonnie; Borrelli, Belinda; Niaura, Raymond

2012-01-01

Aims To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome [Hitsman et al. J Consult Clin Psychol 2003; 71:657–63]. Methods Eligible trials included 14 from our original review and 28 identified through an updated systematic review (2000–2009). We coded for assessment of past MD, exclusion for recent MD episode (MDE; ≤6 months versus no exclusion), duration/modality of cognitive behavioral treatment (CBT; face-to-face versus self-help), and other factors. To minimize influence of experimental treatments that may selectively benefit MD+ smokers, we analyzed placebo/lowest intensity control arms only. Study-specific odds ratios (ORs) for the effect of past MD on short-term (≤3 months) and long-term (≥6 months) abstinence were estimated and combined using random effects. Two-way interaction models of past MD with study methodology and treatment factors were used to evaluate hypothesized moderators of the past MD-abstinence association. Results MD+ smokers had 17% lower odds of short-term abstinence (n=35, OR=0.83, 95% CI=0.72–0.95, p=0.009) and 19% lower odds of long-term abstinence (n=38, OR=0.81, 95% CI=0.67–0.97, p=0.023) than MD− smokers after excluding the sole study of varenicline because of its antidepressant properties. The association between past MD and abstinence was affected by methodological (recent MDE exclusion, type of MD assessment) and treatment (CBT modality) factors. Conclusions Past major depression has a modest adverse effect on abstinence during and after smoking cessation treatment. An increased focus on the identification of effective treatments or treatment adaptations that eliminate this disparity in smoking cessation for MD+ smokers is needed. PMID:23072580

Mediterranean diet as the diet of choice for patients with chronic kidney disease.

PubMed

Chauveau, Philippe; Aparicio, Michel; Bellizzi, Vincenzo; Campbell, Katrina; Hong, Xu; Johansson, Lina; Kolko, Anne; Molina, Pablo; Sezer, Siren; Wanner, Christoph; Ter Wee, Pieter M; Teta, Daniel; Fouque, Denis; Carrero, Juan J

2018-05-01

Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.

Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation.

PubMed

Bromberger, Joyce T; Schott, Laura L; Matthews, Karen A; Kravitz, Howard M; Randolph, John F; Harlow, Sioban; Crawford, Sybil; Green, Robin; Joffe, Hadine

2012-09-01

The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Midlife women with a history of MD are more likely to report heavy bleeding.

Continuum-atomistic simulation of picosecond laser heating of copper with electron heat capacity from ab initio calculation

NASA Astrophysics Data System (ADS)

Ji, Pengfei; Zhang, Yuwen

2016-03-01

On the basis of ab initio quantum mechanics (QM) calculation, the obtained electron heat capacity is implemented into energy equation of electron subsystem in two temperature model (TTM). Upon laser irradiation on the copper film, energy transfer from the electron subsystem to the lattice subsystem is modeled by including the electron-phonon coupling factor in molecular dynamics (MD) and TTM coupled simulation. The results show temperature and thermal melting difference between the QM-MD-TTM integrated simulation and pure MD-TTM coupled simulation. The successful construction of the QM-MD-TTM integrated simulation provides a general way that is accessible to other metals in laser heating.

Clinical features of and risk factors for major depression with history of postpartum episodes in Han Chinese women: A retrospective study.

PubMed

Yang, Fuzhong; Gardner, Charles O; Bigdeli, Tim; Gao, Jingfang; Zhang, Zhen; Tao, Ming; Liu, Ying; Li, Youhui; Wang, Gang; Shi, Jianguo; Gao, Chengge; Zhang, Kerang; Li, Kan; Wang, Xumei; Liu, Lanfen; Sun, Jing; Du, Bo; Shi, Shenxun; Zhang, Jingbei; Wu, Wenyuan; Wang, Xueyi; Shen, Jianhua; Liu, Tiebang; Gu, Danhua; Liang, Wei; Deng, Hong; Pan, Jiyang; Yang, Lijun; Jian, Hu; Jiang, Guoqin; Meng, Huaqing; Miao, Guodong; Li, Yi; Hu, Chunmei; Huang, Guoping; Zhang, Yutang; Chen, Yunchun; Ha, Baowei; Gao, Shu; Fang, Xiang; Mei, Qiyi; Hong, Xiaohong; Yang, Donglin; Liu, Tieqiao; Fengyu, Yu; Zhong, Hui; Sang, Hong; Chen, Guibing; Cai, Min; Song, Yan; Dong, Jicheng; Shen, Zhenmin; Zhang, Wei; Wang, Xiaoping; Pan, Runde; Liu, Xiaojuan; Li, Yi; Liu, Zhengrong; Zhang, Qiwen; Li, Gongying; Flint, Jonathan; Kendler, Kenneth S

2015-09-01

We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2-2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1-1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5-0.8), but more childbirths (OR 1.2). Data were obtained retrospectively through interview and recall bias may have affected the results. MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive. Copyright © 2015. Published by Elsevier B.V.

A novel gene, MdSSK1, as a component of the SCF complex rather than MdSBP1 can mediate the ubiquitination of S-RNase in apple.

PubMed

Yuan, Hui; Meng, Dong; Gu, Zhaoyu; Li, Wei; Wang, Aide; Yang, Qing; Zhu, Yuandi; Li, Tianzhong

2014-07-01

As a core factor in S-RNase-based gametophytic self-incompatibility (GSI), the SCF (SKP1-Cullin1-F-box-Rbx1) complex (including pollen determinant SLF, S-locus-F-box) functions as an E3 ubiquitin ligase on non-self S-RNase. The SCF complex is formed by SKP1 bridging between SLF, CUL1, and Rbx1; however, it is not known whether an SCF complex lacking SKP1 can mediate the ubiquitination of S-RNase. Three SKP1-like genes from pollen were cloned based on the structural features of the SLF-interacting-SKP1-like (SSK) gene and the 'Golden Delicious' apple genome. These genes have a motif of five amino acids following the standard 'WAFE' at the C terminal and, in addition, contain eight sheets and two helices. All three genes were expressed exclusively in pollen. In the yeast two-hybrid and pull-down assays only one was found to interact with MdSFBB and MdCUL1, suggesting it is the SLF-interacting SKP1-like gene in apple which was named MdSSK1. In vitro experiments using MdSSK1, S2-MdSFBB1 (S2-Malus domestica S-locus-F-box brother) and MdCUL1 proteins incubated with S 2-RNase and ubiquitin revealed that the SCF complex ubiquitinylates S-RNase in vitro, while MdSBP1 (Malus domestica S-RNase binding protein 1) could not functionally replace MdSSK1 in the SCF complex in ubiquitinylating S-RNase. According to the above experiments, MdSBP1 is probably the only factor responsible for recognition with S-RNase, while not a component of the SCF complex, and an SCF complex containing MdSSK1 is required for mediating the ubiquitination of S-RNase. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

The CEOS International Directory Network: Progress and Plans, Spring, 1999

NASA Technical Reports Server (NTRS)

Olsen, Lola M.

1999-01-01

The Global Change Master Directory (GCMD) serves as the software development hub for the Committee on Earth observation Satellites' (CEOS) International Directory Network (IDN). The GCMD has upgraded the software for the IDN nodes as Version 7 of the GCMD: MD7-Oracle and MD7-Isite, as well as three other MD7 experimental interfaces. The contribution by DLR representatives (Germany) of the DLR Thesaurus will be demonstrated as an educational tool for use with MD7-Isite. The software will be installed at twelve nodes around the world: Brazil, Argentina, the Netherlands, Canada, France, Germany, Italy, Japan, Australia, New Zealand, Switzerland, and several sites in the United States. Representing NASA for the International Directory Network and the CEOS Data Access Subgroup, NASA's contribution to this international interoperability effort will be updated. Discussion will include interoperability with the CEOS Interoperability Protocol (CIP), features of the latest version of the software, including upgraded capabilities for distributed input by the IDN nodes, installation logistics, "mirroring", population objectives, and future plans.

The CEOS International Directory Network Progress and Plans: Spring, 1999

NASA Technical Reports Server (NTRS)

Olsen, Lola M.

1999-01-01

The Global Change Master Directory (GCMD) serves as the software development hub for the Committee on Earth Observation Satellites' (CEOS) International Directory Network (IDN). The GCMD has upgraded the software for the IDN nodes as Version 7 of the GCMD: MD7-Oracle and MD7-Isite, as well as three other MD7 experimental interfaces. The contribution by DLR representatives (Germany) of the DLR Thesaurus will be demonstrated as an educational tool for use with MD7-Isite. The software will be installed at twelve nodes around the world: Brazil, Argentina, the Netherlands, Canada, France, Germany, Italy, Japan, Australia, New Zealand, Switzerland, and several sites in the United States. Representing NASA for the International Directory Network and the CEOS Data Access Subgroup, NASA's contribution to this international interoperability effort will be updated. Discussion will include interoperability with the CEOS Interoperability Protocol (CIP), features of the latest version of the software, including upgraded capabilities for distributed input by the IDN nodes, installation logistics, "mirroring', population objectives, and future plans.

Sensory trick phenomenon improves motor control in pianists with dystonia: prognostic value of glove-effect

PubMed Central

Paulig, Jakobine; Jabusch, Hans-Christian; Großbach, Michael; Boullet, Laurent; Altenmüller, Eckart

2014-01-01

Musician’s dystonia (MD) is a task-specific movement disorder that causes loss of voluntary motor control while playing the instrument. A subgroup of patients displays the so-called sensory trick: alteration of somatosensory input, e.g., by wearing a latex glove, may result in short-term improvement of motor control. In this study, the glove-effect in pianists with MD was quantified and its potential association with MD-severity and outcome after treatment was investigated. Thirty affected pianists were included in the study. Music instrument digital interface-based scale analysis was used for assessment of fine motor control. Therapeutic options included botulinum toxin, pedagogical retraining and anticholinergic medication (trihexyphenidyl). 19% of patients showed significant improvement of fine motor control through wearing a glove. After treatment, outcome was significantly better in patients with a significant pre-treatment sensory trick. We conclude that the sensory trick may have a prognostic value for the outcome after treatment in pianists with MD. PMID:25295014

Cargo Movement Operations System (CMOS). Final Software Design Document. Increment III. (PC Unix - Air Force Configuration)

DTIC Science & Technology

1991-07-03

required changes to this matrix. CMOS PMO ACCEPTS COMMENT: YES [ ] NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN...this appendix should be updated to include all necessary changes. CMOS PMO ACCEPTS COMMENT: YES [ ] NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION...ERCI ACCEPTS COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ ] CLOSED [ ] ORIGINATOR CONTROL NUMBER: SDD3-0004 PROGRAM OFFICE

76 FR 4719 - Draft Comprehensive Conservation Plan and Environmental Assessment, Selawik National Wildlife...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... public through open houses, meetings, written comments, and personal interviews with community members... Comments Before including your address, phone number, e-mail address, or other personal identifying information in your comment, you should be aware that your entire comment--including your personal identifying...

75 FR 65026 - Draft Comprehensive Conservation Plan and Environmental Assessment, Selawik National Wildlife...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-21

... public through open houses, meetings, written comments, and personal interviews with community members... Comments Before including your address, phone number, e-mail address, or other personal identifying information in your comment, you should be aware that your entire comment--including your personal identifying...

European National Society Cardiovascular Journals

PubMed Central

Alfonso, F.; Ambrosio, G.; Pinto, F.J.; van der Wall, E.E.

2008-01-01

Anesti Kondili MD, Djamaleddine Nibouche MD, Karlen Adamyan MD, Kurt Huber MD, Hugo Ector MD, Izet Masic MD, Rumiana Tarnovska MD, Mario Ivanusa MD, Vladimír Stane˘k MD, Jørgen Videbæk MD, Mohamed Hamed MD, Alexandras Laucevicius MD, Pirjo Mustonen MD, Jean-Yves Artigou MD, Ariel Cohen MD, Mamanti Rogava MD, Michael Böhm MD, Eckart Fleck MD, Gerd Heusch MD, Rainer Klawki MD, Panos Vardas MD, Christodoulos Stefanadis MD, József Tenczer MD, Massimo Chiariello MD, Aleksandras Laucevicius MD, Joseph Elias MD, Halima Benjelloun MD, Olaf Rødevand MD, Piotr Kul/akowski MD, Edvard Apetrei MD, Victor A. Lusov MD, Rafael G. Oganov MD, Velibor Obradovic MD, Gabriel Kamensky MD, Miran F. Kenda MD, Christer Höglund MD, Thomas F. Lüscher MD, René Lerch MD, Moufid Jokhadar MD, Habib Haouala MD, Vedat Sansoy MD, Valentin Shumakov MD, Adam Timmis MD. (European National Society Cardiovascular Journals Editors, see Appendix for complete affiliations) PMID:18665206

Weight Rich-Club Analysis in the White Matter Network of Late-Life Depression with Memory Deficits

PubMed Central

Mai, Naikeng; Zhong, Xiaomei; Chen, Ben; Peng, Qi; Wu, Zhangying; Zhang, Weiru; Ouyang, Cong; Ning, Yuping

2017-01-01

Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients. PMID:28878666

Living with myotonic dystrophy; what can be learned from couples? a qualitative study

PubMed Central

2011-01-01

Background Myotonic dystrophy type 1 (MD1) is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is important to understand their perspective of living with this hereditary, systemic disease. Methods A qualitative study was carried out with a purposive sample of five middle-aged couples, including three men and two women with MD1 and their partners. Fifteen in-depth interviews with persons with MD1, with their partners and with both of them as a couple took place in the homes of the couples in two cities and three villages in the Netherlands in 2009. Results People with MD1 associate this progressive, neuromuscular condition with decreasing abilities, describing physical, cognitive and psychosocial barriers to everyday activities and social participation. Partners highlighted the increasing care giving burden, giving directions and using reminders to compensate for the lack of initiative and avoidant behaviour due to MD1. Couples portrayed the dilemmas and frustrations of renegotiating roles and responsibilities; stressing the importance of achieving a balance between individual and shared activities. All participants experienced a lack of understanding from relatives, friends, and society, including health care, leading to withdrawal and isolation. Health care was perceived as fragmentary, with specialists focusing on specific aspects of the disease rather than seeking to understand the implications of the systemic disorder on daily life. Conclusions Learning from these couples has resulted in recommendations that challenge the tendency to treat MD1 as a condition with primarily physical impairments. It is vital to listen to couples, to elicit the impact of MD1, as a multisystem disorder that influences every aspect of their life together. Couple management, supporting the self-management skills of both partners is proposed as a way of reducing the mismatch between health services and health needs. PMID:21752270

Weight Rich-Club Analysis in the White Matter Network of Late-Life Depression with Memory Deficits.

PubMed

Mai, Naikeng; Zhong, Xiaomei; Chen, Ben; Peng, Qi; Wu, Zhangying; Zhang, Weiru; Ouyang, Cong; Ning, Yuping

2017-01-01

Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients.

Convergence and reproducibility in molecular dynamics simulations of the DNA duplex d(GCACGAACGAACGAACGC)

PubMed Central

Galindo-Murillo, Rodrigo; Roe, Daniel R.; Cheatham, Thomas E.

2014-01-01

Background The structure and dynamics of DNA are critically related to its function. Molecular dynamics (MD) simulations augment experiment by providing detailed information about the atomic motions. However, to date the simulations have not been long enough for convergence of the dynamics and structural properties of DNA. Methods MD simulations performed with AMBER using the ff99SB force field with the parmbsc0 modifications, including ensembles of independent simulations, were compared to long timescale MD performed with the specialized Anton MD engine on the B-DNA structure d(GCACGAACGAACGAACGC). To assess convergence, the decay of the average RMSD values over longer and longer time intervals was evaluated in addition to assessing convergence of the dynamics via the Kullback-Leibler divergence of principal component projection histograms. Results These MD simulations —including one of the longest simulations of DNA published to date at ~44 μs—surprisingly suggest that the structure and dynamics of the DNA helix, neglecting the terminal base pairs, are essentially fully converged on the ~1–5 μs timescale. Conclusions We can now reproducibly converge the structure and dynamics of B-DNA helices, omitting the terminal base pairs, on the μs time scale with both the AMBER and CHARMM C36 nucleic acid force fields. Results from independent ensembles of simulations starting from different initial conditions, when aggregated, match the results from long timescale simulations on the specialized Anton MD engine. General Significance With access to large-scale GPU resources or the specialized MD engine “Anton” it is possibly for a variety of molecular systems to reproducibly and reliably converge the conformational ensemble of sampled structures. PMID:25219455

[Health and socio-economic condition of certified Minamata disease patients, 1999].

PubMed

Ushijima, Kayo; Kitano, Takao; Futatsuka, Makoto

2003-09-01

To clarify the needs and to consider establishing a social support system for patients with Minamata disease (MD), or methylmercury poisoning, by investigating their health and socioeconomic conditions. The total number of people certified as having MD in May 1999 by the Kumamoto and Kagoshima Prefecture Government Committees on MD was 2265. We sent two questionnaires to 917 individuals who were surviving at that time, which corresponded to 40.5% of the total number of MD patients. The first survey sought information on the individual's health-seeking behavior, and the second survey was about their socio-economic conditions and requirements for welfare and medical care in the future. The average age among male patients was 68.0 +/- 13.2 yrs (n = 477) and that among female patients was 71.2 +/- 13.0 yrs (n = 440). The response rates were 45.7% (n = 416) for the first questionnaire and 38.6% (n = 354) for the second questionnaire. Among the MD patients, 71.7% judged their health condition to be 'bad' or 'very bad', and 97.4% received medical treatments that included acupuncture or moxacautery and massage. Regarding the activity of daily living (ADL), which includes 'communicating', 'walking', 'eating', 'use of toilet', 'dressing' and 'taking a bath', the rates of 'independent' were relatively low among those under 49 yrs and those over 75 yrs compared with the other age groups. Many individuals emphasized that they had anxiety about their health and health care in the future. We concluded that the quality of life (QOL) of MD patients was low. It is important to consider developing a social support system for MD patients.

Does the addition of two exercise-focussed home visits to usual care improve outcomes for patients with balance impairments? A randomized controlled trial.

PubMed

Whitbourne, Craig; Shields, Nora; Tacey, Mark; Koh, Kenneth Wz; Lawler, Katherine; Hill, Keith D

2018-03-01

To investigate whether two additional home visits improve outcomes for rehabilitation outpatients with balance impairments compared to usual care. Randomized controlled trial. Outpatient rehabilitation. Fifty with balance impairments. Both groups received usual care including weekly group exercise over eight weeks. The intervention group received two home visits to individualize home exercises. Primary outcome measure was the Balance Outcome Measure for Elder Rehabilitation (BOOMER) score, and secondary outcomes included force platform measures using the NeuroCom Balance Master ® , assessed at baseline, after intervention and three-month follow-up. There was no between-group difference for BOOMER score. There were significant between-group differences in favour of the intervention group for limits of stability reaction time at week 9 (mean difference (MD) -0.27, 95% confidence interval (CI) -0.44 to -0.09) and week 22 (MD -0.28, 95% CI -0.45 to -0.10) and for limits of stability maximal excursion at week 9 (MD 8.66, 95% CI 1.67 to 15.65) and week 22 (MD 14.58, 95% CI 7.59 to 21.57). Significant between-group differences favoured the control group for Clinical Test of Sensory Interaction of Balance at week 9 (MD 0.40, 95% CI 0.13 to 0.66) and week 22 (MD 0.45, 95% CI 0.18 to 0.72) and step quick turn time at week 9 (MD 0.56, 95% CI 0.02 to 1.10). Two exercise-focussed home visits improved some dynamic balance outcomes in older patients with balance impairments. Some outcomes showed significant improvements with small effect sizes in favour of the control group which may be chance findings or because they completed a standard home exercise programme.

Back Schools for chronic non-specific low back pain.

PubMed

Parreira, Patrícia; Heymans, Martijn W; van Tulder, Maurits W; Esmail, Rosmin; Koes, Bart W; Poquet, Nolwenn; Lin, Chung-Wei Christine; Maher, Christopher G

2017-08-03

Many people with low back pain (LBP) become frequent users of healthcare services in their attempt to find treatments that minimise the severity of their symptoms. Back School consists of a therapeutic programme given to groups of people that includes both education and exercise. However, the content of Back School has changed over time and appears to vary widely today. This review is an update of a Cochrane review of randomised controlled trials (RCTs) evaluating the effectiveness of Back School. We split the Cochrane review into two reviews, one focusing on acute and subacute LBP, and one on chronic LBP. The objective of this systematic review was to determine the effect of Back School on pain and disability for adults with chronic non-specific LBP; we included adverse events as a secondary outcome. In trials that solely recruited workers, we also examined the effect on work status. We searched for trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, two other databases and two trials registers to 15 November 2016. We also searched the reference lists of eligible papers and consulted experts in the field of LBP management to identify any potentially relevant studies we may have missed. We placed no limitations on language or date of publication. We included only RCTs and quasi-RCTs evaluating pain, disability, and/or work status as outcomes. The primary outcomes for this update were pain and disability, and the secondary outcomes were work status and adverse events. Two review authors independently performed the 'Risk of bias' assessment of the included studies using the 'Risk of bias' assessment tool recommended by The Cochrane Collaboration. We summarised the results for the short-, intermediate-, and long-term follow-ups. We evaluated the overall quality of evidence using the GRADE approach. For the outcome pain, at short-term follow-up, we found very low-quality evidence that Back School is more effective than no treatment (mean difference (MD) -6.10, 95% confidence interval (CI) -10.18 to -2.01). However, we found very low-quality evidence that there is no significant difference between Back School and no treatment at intermediate-term (MD -4.34, 95% CI -14.37 to 5.68) or long-term follow-up (MD -12.16, 95% CI -29.14 to 4.83). There was very low-quality evidence that Back School reduces pain at short-term follow-up compared to medical care (MD -10.16, 95% CI -19.11 to -1.22). Very low-quality evidence showed there to be no significant difference between Back School and medical care at intermediate-term (MD -9.65, 95% CI -22.46 to 3.15) or long-term follow-up (MD -5.71, 95% CI -20.27 to 8.84). We found very low-quality evidence that Back School is no more effective than passive physiotherapy at short-term (MD 1.96, 95% CI -9.51 to 13.43), intermediate-term (MD -16.89, 95% CI -66.56 to 32.79), or long-term follow-up (MD -12.86, 95% CI -61.22 to 35.50). There was very low-quality evidence that Back School is no better than exercise at short- term follow-up (MD -2.06, 95% CI -14.58 to 10.45). There was low-quality evidence that Back School is no better than exercise at intermediate-term (MD -4.46, 95% CI -19.44 to 10.52) and long-term follow-up (MD 4.58, 95% CI -0.20 to 9.36).For the outcome disability, we found very low-quality evidence that Back School is no more effective than no treatment at intermediate-term (MD -5.92, 95% CI -12.08 to 0.23) and long-term follow-up (MD -7.36, 95% CI -22.05 to 7.34); medical care at short-term (MD -1.19, 95% CI -7.02 to 4.64) and long-term follow-up (MD -0.40, 95% CI -7.33 to 6.53); passive physiotherapy at short-term (MD 2.57, 95% CI -15.88 to 21.01) and intermediate-term follow-up (MD 6.88, 95% CI -4.86 to 18.63); and exercise at short-term (MD -1.65, 95% CI -8.66 to 5.37), intermediate-term (MD 1.57, 95% CI -3.86 to 7.00), and long-term follow-up (MD 4.54, 95% CI -4.44 to 13.52). We found very low-quality evidence of a small difference between Back School and no treatment at short-term follow-up (MD -3.38, 95% CI -6.70 to -0.05) and medical care at intermediate-term follow-up (MD -6.34, 95% CI -10.89 to -1.79). Still, at long-term follow-up there was very low-quality evidence that passive physiotherapy is better than Back School (MD 9.60, 95% CI 3.65 to 15.54).Few studies measured adverse effects. The results were reported as means without standard deviations or group size was not reported. Due to this lack of information, we were unable to statistically pool the adverse events data. Work status was not reported. Due to the low- to very low-quality of the evidence for all treatment comparisons, outcomes, and follow-up periods investigated, it is uncertain if Back School is effective for chronic low back pain. Although the quality of the evidence was mostly very low, the results showed no difference or a trivial effect in favour of Back School. There are myriad potential variants on the Back School approach regarding the employment of different exercises and educational methods. While current evidence does not warrant their use, future variants on Back School may have different effects and will need to be studied in future RCTs and reviews.

Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.

PubMed

Fang, Qilu; Wang, Jingying; Zhang, Yali; Wang, Lintao; Li, Weixin; Han, Jibo; Huang, Weijian; Liang, Guang; Wang, Yi

2018-01-01

Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling. Copyright © 2017. Published by Elsevier B.V.

Childhood trauma and neighborhood-level crime interact in predicting adult posttraumatic stress and major depression symptoms.

PubMed

Lowe, Sarah R; Quinn, James W; Richards, Catherine A; Pothen, John; Rundle, Andrew; Galea, Sandro; Ressler, Kerry J; Koenen, Karestan C; Bradley, Bekh

2016-01-01

Previous research has identified several individual-level factors that modify the risk of childhood trauma on adult psychiatric symptoms, including symptoms of major depression (MD) and posttraumatic stress (PTS). Neighborhood-level factors also influence the impact of individual-level exposures on adult psychopathology. However, no prior studies to our knowledge have explored cross-level interactions between childhood trauma and neighborhood-level factors on MD and PTS symptoms. The purpose of this study was therefore to explore cross-level interactions between a neighborhood-level factor - neighborhood-level crime - and childhood trauma on MD and PTS symptoms. Participants in this study (N=3192) were recruited from a large public hospital, and completed self-report inventories of childhood trauma and MD and PTS symptoms. Participant addresses were mapped onto 2010 census tracts, and data on crime within each tract were collected. Multilevel models found a significant cross-level interaction between childhood trauma and neighborhood crime on MD symptoms, such that the influence of high levels of childhood trauma on MD symptoms was enhanced for participants living in high-crime neighborhoods. Supplementary analyses found variation in the strength of cross-level interaction terms by types of childhood trauma and crime, with the strongest associations including emotional neglect paired with personal and property crime. The results provide preliminary support for interventions that help childhood trauma survivors find housing in less vulnerable neighborhoods and build skills to cope with neighborhood crime. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experience-dependent central vision deficits: Neurobiology and visual acuity.

PubMed

Williams, Kate; Balsor, Justin L; Beshara, Simon; Beston, Brett R; Jones, David G; Murphy, Kathryn M

2015-09-01

Abnormal visual experience during childhood often leads to amblyopia, with strong links to binocular dysfunction that can include poor acuity in both eyes, especially in central vision. In animal models of amblyopia, the non-deprived eye is often considered normal and what limits binocular acuity. This leaves open the question whether monocular deprivation (MD) induces binocular dysfunction similar to what is found in amblyopia. In previous studies of MD cats, we found a loss of excitatory receptors restricted to the central visual field representation in visual cortex (V1), including both eyes' columns. This led us to ask two questions about the effects of MD: how quickly are receptors lost in V1? and is there an impact on binocular acuity? We found that just a few hours of MD caused a rapid loss of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor proteins across all of V1. But after a few days of MD, there was recovery in the visual periphery, leaving a loss of AMPA receptors only in the central region of V1. We reared animals with early MD followed by a long period of binocular vision and found binocular acuity deficits that were greatest in the central visual field. Our results suggest that the greater binocular acuity deficits in the central visual field are driven in part by the long-term loss of AMPA receptors in the central region of V1. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Effects of Music on Pain: A Meta-Analysis.

PubMed

Lee, Jin Hyung

2016-01-01

Numerous meta-analyses have been conducted on the topic of music and pain, with the latest comprehensive study published in 2006. Since that time, more than 70 randomized controlled trials (RCTs) have been published, necessitating a new and comprehensive review. The aim of this meta-analysis was to examine published RCT studies investigating the effect of music on pain. The present study included RCTs published between 1995 and 2014. Studies were obtained by searching 12 databases and hand-searching related journals and reference lists. Main outcomes were pain intensity, emotional distress from pain, vital signs, and amount of analgesic intake. Study quality was evaluated according to the Cochrane Collaboration guidelines. Analysis of the 97 included studies revealed that music interventions had statistically significant effects in decreasing pain on 0-10 pain scales (MD = -1.13), other pain scales (SMD = -0.39), emotional distress from pain (MD = -10.83), anesthetic use (SMD = -0.56), opioid intake (SMD = -0.24), non-opioid intake (SMD = -0.54), heart rate (MD = -4.25), systolic blood pressure (MD = -3.34), diastolic blood pressure (MD = -1.18), and respiration rate (MD = -1.46). Subgroup and moderator analyses yielded additional clinically informative outcomes. Considering all the possible benefits, music interventions may provide an effective complementary approach for the relief of acute, procedural, and cancer/chronic pain in the medical setting. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Childhood Trauma and Neighborhood-Level Crime Interact in Predicting Adult Posttraumatic Stress and Major Depression Symptoms

PubMed Central

Lowe, Sarah R.; Quinn, James W.; Richards, Catherine A.; Pothen, John; Rundle, Andrew; Galea, Sandro; Ressler, Kerry J.; Koenen, Karestan C.; Bradley, Bekh

2015-01-01

Previous research has identified several individual-level factors that modify the risk of childhood trauma on adult psychiatric symptoms, including symptoms of major depression (MD) and posttraumatic stress (PTS). Neighborhood-level factors also influence the impact of individual-level exposures on adult psychopathology. However, no prior studies to our knowledge have explored cross-level interactions between childhood trauma and neighborhood-level factors on MD and PTS symptoms. The purpose of this study was therefore to explore cross-level interactions between a neighborhood-level factor – neighborhood-level crime – and childhood trauma on MD and PTS symptoms. Participants in this study (N = 3,192) were recruited from a large public hospital, and completed self-report inventories of childhood trauma and MD and PTS symptoms. Participant addresses were mapped onto 2010 census tracts, and data on crime within each tract was collected. Multilevel models found a significant cross-level interaction between childhood trauma and neighborhood crime on MD symptoms, such that the influence of high levels of childhood trauma on MD symptoms was enhanced for participants living in high-crime neighborhoods. Supplementary analyses found variation in the strength of cross-level interaction terms by types of childhood trauma and crime, with the strongest associations including emotional neglect paired with personal and property crime. The results provide preliminary support for interventions that help childhood trauma survivors find housing in less vulnerable neighborhoods and build skills to cope with neighborhood crime. PMID:26499372

Chronic methadone use, poor bowel visualization and failed colonoscopy: A preliminary study

PubMed Central

Verma, Siddharth; Fogel, Joshua; Beyda, David J; Bernstein, Brett; Notar-Francesco, Vincent; Mohanty, Smruti R

2012-01-01

AIM: To examine effects of chronic methadone usage on bowel visualization, preparation, and repeat colonoscopy. METHODS: In-patient colonoscopy reports from October, 2004 to May, 2009 for methadone dependent (MD) patients were retrospectively evaluated and compared to matched opioid naive controls (C). Strict criteria were applied to exclude patients with risk factors known to cause constipation or gastric dysmotility. Colonoscopy reports of all eligible patients were analyzed for degree of bowel visualization, assessment of bowel preparation (good, fair, or poor), and whether a repeat colonoscopy was required. Bowel visualization was scored on a 4 point scale based on multiple prior studies: excellent = 1, good = 2, fair = 3, or poor = 4. Analysis of variance (ANOVA) and Pearson χ2 test were used for data analyses. Subgroup analysis included correlation between methadone dose and colonoscopy outcomes. All variables significantly differing between MD and C groups were included in both univariate and multivariate logistic regression analyses. P values were two sided, and < 0.05 were considered statistically significant. RESULTS: After applying exclusionary criteria, a total of 178 MD patients and 115 C patients underwent a colonoscopy during the designated study period. A total of 67 colonoscopy reports for MD patients and 72 for C were included for data analysis. Age and gender matched controls were randomly selected from this population to serve as controls in a numerically comparable group. The average age for MD patients was 52.2 ± 9.2 years (range: 32-72 years) years compared to 54.6 ± 15.5 years (range: 20-81 years) for C (P = 0.27). Sixty nine percent of patients in MD and 65% in C group were males (P = 0.67). When evaluating colonoscopy reports for bowel visualization, MD patients had significantly greater percentage of solid stool (i.e., poor visualization) compared to C (40.3% vs 6.9%, P < 0.001). Poor bowel preparation (35.8% vs 9.7%, P < 0.001) and need for repeat colonoscopy (32.8% vs 12.5%, P = 0.004) were significantly higher in MD group compared to C, respectively. Under univariate analysis, factors significantly associated with MD group were presence of fecal particulate [odds ratio (OR), 3.89, 95% CI: 1.33-11.36, P = 0.01] and solid stool (OR, 13.5, 95% CI: 4.21-43.31, P < 0.001). Fair (OR, 3.82, 95% CI: 1.63-8.96, P = 0.002) and poor (OR, 8.10, 95% CI: 3.05-21.56, P < 0.001) assessment of bowel preparation were more likely to be associated with MD patients. Requirement for repeat colonoscopy was also significant higher in MD group (OR, 3.42, 95% CI: 1.44-8.13, P = 0.01). In the multivariate analyses, the only variable independently associated with MD group was presence of solid stool (OR, 7.77, 95% CI: 1.66-36.47, P = 0.01). Subgroup analysis demonstrated a general trend towards poorer bowel visualization with higher methadone dosage. ANOVA analysis demonstrated that mean methadone dose associated with presence of solid stool (poor visualization) was significantly higher compared to mean dosage for clean colon (excellent visualization, P = 0.02) or for those with liquid stool only (good visualization, P = 0.01). CONCLUSION: Methadone dependence is a risk factor for poor bowel visualization and leads to more repeat colonoscopies. More aggressive bowel preparation may be needed in MD patients. PMID:22969198

Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

PubMed

Rubini, Alessandro; Bosco, Gerardo; Lodi, Alessandra; Cenci, Lorenzo; Parmagnani, Andrea; Grimaldi, Keith; Zhongjin, Yang; Paoli, Antonio

2015-12-01

The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p < 0.05) in RER was observed after 20 and 40 days in the KD group, but not in the MD group. In the KD group, significant reductions were observed for both carbon dioxide output and PETCO2, however, there was no significant change in VO2, VCO2, and REE. While both diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

Marek’s disease virus induces transient atrophy of cecal tonsils

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens caused by an immunosupperessive alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include bursal/thymic atrophy and neurological disorders. The cecal tonsils (CT) are the largest lymphoid aggregates of avia...

Observer Comments Provided at the Peer Consultation Workshop (Appendix E)

EPA Pesticide Factsheets

The peer consultation workshop included three observer comment periods, one on the first day of the workshop and two on the second day of the workshop. This appendix includes verbatim transcripts (to the extent that specific remarks were audible from recordings) of the observer comments, in the order the comments were given.

Cross-sectional-derived determinants of satisfaction with physician-scientist training among Canadian MD/PhD graduates.

PubMed

Twa, David D W; Skinnider, Michael A; Squair, Jordan W; Lukac, Christine D

2017-01-01

Although MD/PhD programs require considerable commitment on behalf of students and learning institutions, they serve as an integral means of training future physician-scientists; individuals who engage in translational medicine. As attrition from these programs has longstanding effects on the community of translational medicine and comes at substantial cost to MD/PhD programs, we aimed to identify determinants that were associated with satisfaction among MD/PhD graduates, a feature that might inform on limiting program attrition. Anonymized data from a national survey of 139 Canadian MD/PhD alumni was analyzed. Factor analysis was conducted to evaluate the reliability of three questions that measured satisfaction and logistic regression was used to assess the association of outcomes with 17 independent determinants. Eighty-one percent of graduates were satisfied with MD/PhD training. Factor analysis confirmed the reliability of the questions measuring satisfaction. Determinants of self-reported satisfaction with physician-scientist training included co-authorship of more than six manuscripts during MD/PhD training. Additionally, protected research time at the place of current appointment was strongly associated with agreement that MD/PhD training had helped career progression. Demographic variables were not associated with any satisfaction indicator. Taken together, the majority of Canadian MD/PhD graduates are satisfied with their physician-scientist training. Project collaboration leading to co-authorships and protected research time were strongly associated with training satisfaction among graduates. If the value of collaboration can be realized among current and future physician-scientist trainees who are dissatisfied with their training, this might ultimately reduce program attrition.

Frequency of a natural truncated allele of MdMLO19 in the germplasm of Malus domestica.

PubMed

Pessina, Stefano; Palmieri, Luisa; Bianco, Luca; Gassmann, Jennifer; van de Weg, Eric; Visser, Richard G F; Magnago, Pierluigi; Schouten, Henk J; Bai, Yuling; Riccardo Velasco, R; Malnoy, Mickael

2017-01-01

Podosphaera leucotricha is the causal agent of powdery mildew (PM) in apple. To reduce the amount of fungicides required to control this pathogen, the development of resistant apple cultivars should become a priority. Resistance to PM was achieved in various crops by knocking out specific members of the MLO gene family that are responsible for PM susceptibility (S-genes). In apple, the knockdown of MdMLO19 resulted in PM resistance. However, since gene silencing technologies such as RNAi are perceived unfavorably in Europe, a different approach that exploits this type of resistance is needed. This work evaluates the presence of non-functional naturally occurring alleles of MdMLO19 in apple germplasm. The screening of the re-sequencing data of 63 apple individuals led to the identification of 627 single nucleotide polymorphisms (SNPs) in five MLO genes ( MdMLO5, MdMLO7, MdMLO11, MdMLO18 , and MdMLO19 ), 127 of which were located in exons. The T-1201 insertion of a single nucleotide in MdMLO19 caused the formation of an early stop codon, resulting in a truncated protein lacking 185 amino acids, including the calmodulin-binding domain. The presence of the insertion was evaluated in 115 individuals. It was heterozygous in 64 and homozygous in 25. Twelve of the 25 individuals carrying the insertion in homozygosity were susceptible to PM. After barley, pea, cucumber, and tomato, apple would be the fifth species for which a natural non-functional mlo allele has been found.

Exciting Normal Distribution

ERIC Educational Resources Information Center

Fuchs, Karl Josef; Simonovits, Reinhard; Thaller, Bernd

2008-01-01

This paper describes a high school project where the mathematics teaching and learning software M@th Desktop (MD) based on the Computer Algebra System Mathematica was used for symbolical and numerical calculations and for visualisation. The mathematics teaching and learning software M@th Desktop 2.0 (MD) contains the modules Basics including tools…

Immune responses in cecal tonsils of MDV-infected chickens

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic '-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. Clinical signs of MD include dep...

A Mediterranean Diet Model in Australia: Strategies for Translating the Traditional Mediterranean Diet into a Multicultural Setting

PubMed Central

Kucianski, Teagan; Moschonis, George; Tierney, Audrey C.; Itsiopoulos, Catherine

2018-01-01

Substantial evidence supports the effect of the Mediterranean Diet (MD) for managing chronic diseases, although trials have been primarily conducted in Mediterranean populations. The efficacy and feasibility of the Mediterranean dietary pattern for the management of chronic diseases has not been extensively evaluated in non-Mediterranean settings. This paper aims to describe the development of a MD model that complies with principles of the traditional MD applied in a multiethnic context. Optimal macronutrient and food-based composition was defined, and a two-week menu was devised incorporating traditional ingredients with evidence based on improvements in chronic disease management. Strategies were developed for the implementation of the diet model in a multiethnic population. Consistent with the principles of a traditional MD, the MD model was plant-based and high in dietary fat, predominantly monounsaturated fatty acids from extra virgin olive oil. Fruits, vegetables and wholegrains were a mainstay, and moderate amounts of nuts and seeds, fish, dairy and red wine were recommended. The diet encompassed key features of the MD including cuisine, biodiversity and sustainability. The MD model preserved traditional dietary components likely to elicit health benefits for individuals with chronic diseases, even with the adaptation to an Australian multiethnic population. PMID:29642557

A Mediterranean Diet Model in Australia: Strategies for Translating the Traditional Mediterranean Diet into a Multicultural Setting.

PubMed

George, Elena S; Kucianski, Teagan; Mayr, Hannah L; Moschonis, George; Tierney, Audrey C; Itsiopoulos, Catherine

2018-04-09

Substantial evidence supports the effect of the Mediterranean Diet (MD) for managing chronic diseases, although trials have been primarily conducted in Mediterranean populations. The efficacy and feasibility of the Mediterranean dietary pattern for the management of chronic diseases has not been extensively evaluated in non-Mediterranean settings. This paper aims to describe the development of a MD model that complies with principles of the traditional MD applied in a multiethnic context. Optimal macronutrient and food-based composition was defined, and a two-week menu was devised incorporating traditional ingredients with evidence based on improvements in chronic disease management. Strategies were developed for the implementation of the diet model in a multiethnic population. Consistent with the principles of a traditional MD, the MD model was plant-based and high in dietary fat, predominantly monounsaturated fatty acids from extra virgin olive oil. Fruits, vegetables and wholegrains were a mainstay, and moderate amounts of nuts and seeds, fish, dairy and red wine were recommended. The diet encompassed key features of the MD including cuisine, biodiversity and sustainability. The MD model preserved traditional dietary components likely to elicit health benefits for individuals with chronic diseases, even with the adaptation to an Australian multiethnic population.

The relationship between anabolic androgenic steroids and muscle dysmorphia: a review.

PubMed

Rohman, Lebur

2009-01-01

This review explores the condition of muscle dysmorphia (MD) and its relationship with anabolic androgenic steroids (AAS). Particular emphasis is placed upon whether anabolic steroids are a predisposing, precipitating or perpetuating factor of MD. Furthermore, psychiatric complications of AAS abuse are examined. The current evidence from the literature suggests that AAS (ab)use is possibly a perpetuating factor in the evolution of MD. Psychiatric complications of AAS include mood and behavior changes, perceptual abnormalities, and withdrawal symptoms. In addition, there appears to be a credible dependence theory to AAS in fruition.

52 Loop-mediated isothermal amplification PCR (LAMP) for the rapid identification of invasive meningococcal disease in the emergency department.

PubMed

Waterfield, Thomas; Patenall, Bethany; McKenna, James; Fairley, Derek

2017-12-01

Despite successful vaccination programmes meningococcal disease (MD) remains the leading infectious cause of septicaemia and death in children in the UK and Ireland. 1,2 The early diagnosis of MD significantly improves outcomes with reduced morbidity and mortality. 1,2 The early stages of MD are often indistinguishable from a simple viral illness making an early positive diagnosis of MD difficult. 1 Hibergene have developed a commercially available bedside Loop-mediated isothermal AMPlification PCR (LAMP-MD) test that is a highly sensitive 0.89 (95%CI 0.72-0.96) and specific 1.0 (95%CI 0.97-1.0) for identifying children with invasive MD (4) (figure 1).emermed;34/12/A895-a/F1F1F1Figure 1 AIMS: The aims of this RCEM funded study were:Assess the ease of use and suitability for the EDDetermine the time taken to perform the testIndependently verify LAMP-MD performance against TaqMan quantitative PCR. The LAMP-MD was assessed for practicality and ease of use within the ED including an assessment of training needs, footprint and health and safety requirements.For verification of the Hibergene LAMP-MD analyser and assay we used dry nasopharyngeal swabs sent for viral screening. Additional verification was undertaken using N. meningitidis genomic DNA spiked over a range of concentrations. This included serotypes A, B, C, W, X and Y and a dilution series to determine the limit of detection. All samples were then analysed using real time TaqMan qPCR. The LAMP-MD analyser was easy to use and could be accommodated in the EDThe mean time for detection of Meningococcal DNA was 14.01 minDetection of meningococcal serogroups A, B, C, W, X and Z was confirmedThe detection limit for dry nasopharyngeal swabs was below 2 genomic copies per µlNo non-specific amplification was observed in 17 randomly selected negative clinical swabsThe LAMP-MD assay was 100% sensitive and specific relative to real-time TaqMAN PCR. LAMP-MD is a practical, rapid point of care test that can reliably detect all Meningococcal serotypes in less than 15 min.Funding has been secured to perform a PERUKI supported study to investigate the potential for LAMP-MD in the diagnosis of meningococcal disease in children. Meningitis Research Foundation. Meningococcal Meningitis and Septicaemia Guidance Notes 2014.Ó Maoldomhnaigh, et al. Invasive meningococcal disease in children in Ireland . PMID: 27566800.NICE. Management of petechial rash .Bourke TW, et al. Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children . PMID: 25728843. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A ‘modified de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer

PubMed Central

Cheeseman, S L; Joel, S P; Chester, J D; Wilson, G; Dent, J T; Richards, F J; Seymour, M T

2002-01-01

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified ‘Modified de Gramont’ (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m−2), then ambulatory 46-h fluorouracil infusion (2000–3600 mg m−2, cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m−2. Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m−2 bolus + 2800 mg m−2 46-h infusion. A lower dose of 400 mg m−2 bolus + 2400 mg m−2 infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC0–48 h) at this lower dose is equivalent to dG. With OxMdG, grade 3–4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial. British Journal of Cancer (2002) 87, 393–399. doi:10.1038/sj.bjc.6600467 www.bjcancer.com © 2002 Cancer Research UK PMID:12177775

75 FR 4133 - Generalized System of Preferences (GSP): Notice Regarding the Review of a Petition To Withdraw...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-26

.... Opportunities for Public Comment The GSP Subcommittee of the TPSC invites written comments in support of or in... that should be included in written comments. Submissions should comply with the GSP regulations, except... response to this notice (including written comments and all business confidential submissions), must be...

The health care response to pandemic influenza.

PubMed

Barnitz, Laura; Berkwits, Michael

2006-07-18

The threat of an H5N1 influenza virus (avian flu) pandemic is substantial. The success of the current U.S. influenza pandemic response plan depends on effective coordination among state and local public health authorities and individual health care providers. This article is a summary of a public policy paper developed by the American College of Physicians to address issues in the U.S. Department of Health and Human Services Pandemic Influenza Plan that involve physicians. The College's positions call for the following: 1) development of local public health task forces that include physicians representing all specialties and practice settings; 2) physician access to 2-way communication with public health authorities and to information technology tools for diagnosis and syndrome surveillance; 3) clear identification and authorization of agencies to process licensing and registration of volunteer physicians; 4) clear guidelines for overriding standard procedures for confidentiality and consent in the interest of the public's health; 5) clear and fair infection control measures that do not create barriers to care; 6) analysis of and solutions to current problems with seasonal influenza vaccination programs as a way of developing a maximally efficient pandemic flu vaccine program; 7) federal funding to provide pandemic flu vaccine for the entire U.S. population and antiviral drugs for 25% of the population; and 8) planning for health care in alternative, nonhospital settings to prevent a surge in demand for hospital care that exceeds supply. *This paper is an abridged version of a full-text position paper (available at http://www.acponline.org/college/pressroom/as06/pandemic_policy.pdf) written by Laura Barnitz, BJ, MA, and updated and adapted for publication in Annals of Internal Medicine by Michael Berkwits, MD, MSCE. The original position paper was developed for the Health and Public Policy Committee of the American College of Physicians: Jeffrey P. Harris, MD (Chair); David L. Bronson, MD (Vice Chair); CPT Julie Ake, MD; Patricia P. Barry, MD; Molly Cooke, MD; Herbert S. Diamond, MD; Joel S. Levine, MD; Mark E. Mayer, MD; Thomas McGinn, MD; Robert M. McLean, MD; Ashley E. Starkweather; and Frederick E. Turton, MD. It was approved by the Board of Regents on 3 April 2006.

Alcohol acyl transferase 1 links two distinct volatile pathways that produce esters and phenylpropenes in apple fruit.

PubMed

Yauk, Yar-Khing; Souleyre, Edwige J F; Matich, Adam J; Chen, Xiuyin; Wang, Mindy Y; Plunkett, Blue; Dare, Andrew P; Espley, Richard V; Tomes, Sumathi; Chagné, David; Atkinson, Ross G

2017-07-01

Fruit accumulate a diverse set of volatiles including esters and phenylpropenes. Volatile esters are synthesised via fatty acid degradation or from amino acid precursors, with the final step being catalysed by alcohol acyl transferases (AATs). Phenylpropenes are produced as a side branch of the general phenylpropanoid pathway. Major quantitative trait loci (QTLs) on apple (Malus × domestica) linkage group (LG)2 for production of the phenylpropene estragole and volatile esters (including 2-methylbutyl acetate and hexyl acetate) both co-located with the MdAAT1 gene. MdAAT1 has previously been shown to be required for volatile ester production in apple (Plant J., 2014, https://doi.org/10.1111/tpj.12518), and here we show it is also required to produce p-hydroxycinnamyl acetates that serve as substrates for a bifunctional chavicol/eugenol synthase (MdoPhR5) in ripe apple fruit. Fruit from transgenic 'Royal Gala' MdAAT1 knockdown lines produced significantly reduced phenylpropene levels, whilst manipulation of the phenylpropanoid pathway using MdCHS (chalcone synthase) knockout and MdMYB10 over-expression lines increased phenylpropene production. Transient expression of MdAAT1, MdoPhR5 and MdoOMT1 (O-methyltransferase) genes reconstituted the apple pathway to estragole production in tobacco. AATs from ripe strawberry (SAAT1) and tomato (SlAAT1) fruit can also utilise p-coumaryl and coniferyl alcohols, indicating that ripening-related AATs are likely to link volatile ester and phenylpropene production in many different fruit. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Atmospheric Pressure and Onset of Episodes of Menière's Disease - A Repeated Measures Study.

PubMed

Gürkov, Robert; Strobl, Ralf; Heinlin, Nina; Krause, Eike; Olzowy, Bernhard; Koppe, Christina; Grill, Eva

2016-01-01

External changes of air pressure are transmitted to the middle and inner ear and may be used therapeutically in Menière's disease, one of the most common vertigo disorders. We analyzed the possible relationship of atmospheric pressure and other meteorological parameters with the onset of MD vertigo episodes in order to determine whether atmospheric pressure changes play a role in the occurrence of MD episodes. Patients of a tertiary outpatient dizziness clinic diagnosed with MD were asked to keep a daily vertigo diary to document MD episodes (2004-2009). Local air pressure, absolute temperature and dew point temperature were acquired on an hourly basis. Change in meteorological parameters was conceptualized as the maximum difference in a 24 hour time frame preceding each day. Effects were estimated using additive mixed models with a random participant effect. We included lagged air parameters, age, sex, weekday and season in the model. A total of 56 persons (59% female) with mean age 54 years were included. Mean follow-up time was 267 days. Persons experienced on average 10.3 episodes during the observation period (median 8). Age and change in air pressure were significantly associated with vertigo onset risk (Odds Ratio = 0.979 and 1.010). We could not show an effect of sex, weekday, season, air temperature, and dew point temperature. Change in air pressure was significantly associated with onset of MD episodes, suggesting a potential triggering mechanism in the inner ear. MD patients may possibly use air pressure changes as an early warning system for vertigo attacks in the future.

Mediterranean Diet and Prevention of Chronic Diseases

PubMed Central

Romagnolo, Donato F.; Selmin, Ornella I.

2017-01-01

A large body of research data suggests that traditional dietary habits and lifestyle unique to the Mediterranean region (Mediterranean diet, MD) lower the incidence of chronic diseases and improve longevity. These data contrast with troubling statistics in the United States and other high income countries pointing to an increase in the incidence of chronic diseases and the projected explosion in cost of medical care associated with an aging population. In 2013, the MD was inscribed by UNESCO in the “Representative List of the Intangible Cultural Heritage of Humanity.” The 2015–2020 Dietary Guidelines for Americans included the MD as a healthy dietary pattern. Therefore, specific objectives of this article are to provide an overview of the nutritional basis of this healthful diet, its metabolic benefits, and its role in multiple aspects of disease prevention and healthy aging. Whereas recommendations about the MD often focus on specific foods or bioactive compounds, we suggest that the eating pattern as a whole likely contributes to the health promoting effects of the MD. PMID:29051674

Delayed Immunomodulatory Effect of Cow Milk-Free Diet in Ménière's Disease.

PubMed

Di Berardino, Federica; Zanetti, Diego

2018-02-01

Since 1930, dietary modification has been proposed as adjunct treatment in Ménière's disease (MD) with different and controversial results. We report the case of a 42-year-old female suffering from definite MD and intermittent seasonal allergic rhino-conjunctivitis because it highlights the importance of evaluating the different combinations of defined causative elements in an atopic patient with MD. An immunological and audiological evaluation was performed, including pure-tone, speech, and immittance audiometry; glycerol dehydration test; bithermal caloric testing; video head impulse test; cervical vestibular evoked myogenic potentials; static posturography; and Dizziness Handicap Inventory questionnaire. A milk-free diet was crucial to relief from MD symptoms and a cow's milk challenge test was able to evoke them but vestibukar symptoms persist. The effect of dietary modification was evident only after specific immunotherapies against other allergens. This highlights the importance of evaluating different combinations of defined causative elements in the allergic treatment of MD.

Comparison of Phase Field Crystal and Molecular Dynamics Simulations for a Shrinking Grain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radhakrishnan, Balasubramaniam; Gorti, Sarma B; Nicholson, Don M

2012-01-01

The Phase-Field Crystal (PFC) model represents the atomic density as a continuous function, whose spatial distribution evolves at diffusional, rather than vibrational time scales. PFC provides a tool to study defect interactions at the atomistic level but over longer time scales than in molecular dynamics (MD). We examine the behavior of the PFC model with the goal of relating the PFC parameters to physical parameters of real systems, derived from MD simulations. For this purpose we model the phenomenon of the shrinking of a spherical grain situated in a matrix. By comparing the rate of shrinking of the central grainmore » using MD and PFC we obtain a relationship between PFC and MD time scales for processes driven by grain boundary diffusion. The morphological changes in the central grain including grain shape and grain rotation are also examined in order to assess the accuracy of the PFC in capturing the evolution path predicted by MD.« less

76 FR 57727 - Notice of Competing Preliminary Permit Applications Accepted for Filing and Soliciting Comments...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... maximum of 725 cfs, at 4.6 feet of net head; (4) a tailrace, which would include a submerged dike to.../docs-filing/efiling.asp . Commenters can submit brief comments up to 6,000 characters, without prior registration, using the eComment system at http://www.ferc.gov/docs-filing/ecomment.asp . You must include your...

76 FR 53942 - Richard A. Herbert, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 09-33] Richard A. Herbert, M.D.; Decision and Order On June 15, 2010, Administrative Law Judge (ALJ) Mary Ellen Bittner issued the attached recommended decision. Thereafter, Respondent filed Exceptions to the ALJ's decision. Having reviewed the entire record including Respondent's...

Isolation and characterization of a novel glycosyltransferase that converts phloretin to phlorizin, a potent antioxidant in apple.

PubMed

Jugdé, Hélène; Nguy, Danny; Moller, Isabel; Cooney, Janine M; Atkinson, Ross G

2008-08-01

The dihydrochalcone phlorizin (phloretin 2'-glucoside) contributes to the flavor, color and health benefits of apple fruit and processed products. A genomics approach was used to identify the gene MdPGT1 in apple (Malus x domestica) with homology to the UDP-glycosyltransferase 88 family of uridine diphosphate glycosyltransferases that show specificity towards flavonoid substrates. Expressed sequence tags for MdPGT1 were found in all tissues known to produce phlorizin including leaf, flower and fruit. However, the highest expression was measured by quantitative PCR in apple root tissue. The recombinant MdPGT1 enzyme expressed in Escherichia coli glycosylated phloretin in the presence of [(3)H]-UDP-glucose, but not other apple antioxidants, including quercetin, naringenin and cyanidin. The product of phloretin and UDP-glucose co-migrated with an authentic phlorizin standard. LC/MS indicated that MdPGT1 could glycosylate phloretin in the presence of three sugar donors: UDP-glucose, UDP-xylose and UDP-galactose. This is the first report of functional characterization of a UDP-glycosyltransferase that utilizes a dihydrochalcone as its primary substrate.

Variations in Patterns of Utilization and Charges for the Care of Low Back Pain in North Carolina, 2000 to 2009: A Statewide Claims' Data Analysis.

PubMed

Hurwitz, Eric L; Li, Dongmei; Guillen, Jenni; Schneider, Michael J; Stevans, Joel M; Phillips, Reed B; Phelan, Shawn P; Lewis, Eugene A; Armstrong, Richard C; Vassilaki, Maria

2016-05-01

The purpose of the study was to compare utilization and charges generated by medical doctors (MD), doctors of chiropractic (DC) and physical therapists (PT) by patterns of care for the treatment of low back pain in North Carolina. This was an analysis of low-back-pain-related closed claim data from the North Carolina State Health Plan for Teachers and State Employees from 2000 to 2009. Data were extracted from Blue Cross Blue Shield of North Carolina for the North Carolina State Health Plan using International Classification of Diseases, 9th Revision diagnostic codes for uncomplicated low back pain (ULBP) and complicated low back pain (CLBP). Care patterns with single-provider types and no referrals incurred the least charges on average for both ULBP and CLBP. When care did not include referral providers or services, for ULBP, MD and DC care was on average $465 less than MD and PT care. For CLBP, MD and DC care averaged $965 more than MD and PT care. However, when care involved referral providers or services, MD and DC care was on average $1600 less when compared to MD and PT care for ULBP and $1885 less for CLBP. Risk-adjusted charges (available 2006-2009) for patients in the middle quintile of risk were significantly less for DC care patterns. Chiropractic care alone or DC with MD care incurred appreciably fewer charges for ULBP than MD care with or without PT care. This finding was reversed for CLBP. Adjusted charges for both ULBP and CLBP patients were significantly lower for DC patients. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Wnt4 coordinates directional cell migration and extension of the Müllerian duct essential for ontogenesis of the female reproductive tract

PubMed Central

Prunskaite-Hyyryläinen, Renata; Skovorodkin, Ilya; Xu, Qi; Miinalainen, Ilkka; Shan, Jingdong; Vainio, Seppo J.

2016-01-01

The Müllerian duct (MD) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. Several wingless-type mouse mammary tumor virus (MMTV) integration site family member (Wnt) genes, including Wnt4, Wnt5a and Wnt7a, are involved in the development of MD and its derivatives, with Wnt4 particularly critical, since the MD fails to develop in its absence. We use, here, Wnt4EGFPCre-based fate mapping to demonstrate that the MD tip cells and the subsequent MD cells are derived from Wnt4+ lineage cells. Moreover, Wnt4 is required for the initiation of MD-forming cell migration. Application of anti-Wnt4 function-blocking antibodies after the initiation of MD elongation indicated that Wnt4 is necessary for the elongation as well, and consistent with this, cell culture wound-healing assays with NIH3T3 cells overexpressing Wnt4 promoted cell migration by comparison with controls. In contrast to the Wnt4 null embryos, some Wnt4monomeric cherry/monomeric cherry (Wnt4mCh/mCh) hypomorphic mice survived to adulthood and formed MD in ∼45% of cases. Nevertheless, the MD of the Wnt4mCh/mCh females had altered cell polarization and basement membrane deposition relative to the controls. Examination of the reproductive tract of the Wnt4mCh/mCh females indicated a poorly coiled oviduct, absence of the endometrial glands and an undifferentiated myometrium, and these mice were prone to develop a hydro-uterus. In conclusion, the results suggest that the Wnt4 gene encodes signals that are important for various aspects of female reproductive tract development. PMID:26721931

Herpes virus and Ménière's disease.

PubMed

Gartner, M; Bossart, W; Linder, T

2008-01-01

The main goal of this study was to examine the vestibular ganglia from patients with intractable classic Ménière's disease (MD) for the presence or absence of DNA from three neurotropic viruses herpes simplex virus 1 and 2 (HSV1, HSV2) and varicella zoster virus (VZV) and to investigate the hypothesis that MD is associated with virus reactivation within Scarpa's ganglion. Polymerase chain reaction (PCR) was performed with nested primer sets specific for viral genomic DNA of HSV1, HSV2 and VZV in biopsies of the ganglion scarpae of patients with MD who underwent vestibular neurectomy. Included were patients with MD classified as definite MD according to American Academy of Otolaryngology/Head and Neck Surgery criteria. The ganglion scarpae and ganglion geniculi harvested at autopsy from patients without history of MD or facial palsy served as control specimens. No viral DNA was detected in the vestibular ganglion of 7 patients with definite MD. In 34% of the vestibular ganglia of the control group we detected either HSV1 or VZV. Only one Scarpa's ganglion had both viruses present at the same time. Thirty-two out of 34 ganglia from the geniculate segment of the facial nerve contained either HSV1 and/or VZV genomic DNA. Eight specimens contained both viruses simultaneously. Altogether viral DNA was found in 94% of ganglia. Viral genomic DNA of HSV2 was not detected. Although HSV and VZV appear to be present in many ganglion cells throughout the human body, we were unable to find genomic DNA of these viruses in patients with definite MD and disabling vertigo, who underwent vestibular neurectomy. Based on these results, reactivation of HSV1 and VZV in the vestibular ganglion does not seem to play a role in the pathogenesis of MD. (c) 2008 S. Karger AG, Basel

Does psychosis increase the risk of suicide in patients with major depression? A systematic review.

PubMed

Zalpuri, Isheeta; Rothschild, Anthony J

2016-07-01

Over the years studies have shown conflicting results about the risk of suicide in psychotic depression (MD-psych). To understand this association, we undertook a comprehensive review of the literature to ascertain whether individuals with MD-psych have higher rates of completed suicides, suicide attempts or suicidal ideation compared to those with non-psychotic depression (MD-nonpsych). We searched Pubmed, PsycINFO and Ovid in English language, from 1946-October 2015. Studies were included if suicidal ideation, attempts or completed suicides were assessed. During the acute episode of depression, patients with MD-psych have higher rates of suicide, suicide attempts, and suicidal ideation than patients with MD-nonpsych, especially when the patient is hospitalized on an inpatient psychiatric unit. Studies done after the acute episode has resolved are less likely to show this difference, likely due to patients having received treatment. Diagnostic interviews were not conducted in all studies. Many studies did not report whether psychotic symptoms in MD-psych patients were mood-congruent or mood-incongruent; hence it is unclear whether the type of delusion increases suicide risk. Studies did not describe whether MD-psych patients experienced command hallucinations encouraging them to engage in suicidal behavior. Only 24 studies met inclusion criteria; several of them had small sample size and a quality score of zero, hence impacting validity. This review indicates that the seemingly conflicting data in suicide risk between MD-psych and MD-nonpsych in previous studies appears to be related to whether one looks at differences during the acute episode or over the long-term. Copyright © 2016 Elsevier B.V. All rights reserved.

Accelerated molecular dynamics simulations of ligand binding to a muscarinic G-protein-coupled receptor.

PubMed

Kappel, Kalli; Miao, Yinglong; McCammon, J Andrew

2015-11-01

Elucidating the detailed process of ligand binding to a receptor is pharmaceutically important for identifying druggable binding sites. With the ability to provide atomistic detail, computational methods are well poised to study these processes. Here, accelerated molecular dynamics (aMD) is proposed to simulate processes of ligand binding to a G-protein-coupled receptor (GPCR), in this case the M3 muscarinic receptor, which is a target for treating many human diseases, including cancer, diabetes and obesity. Long-timescale aMD simulations were performed to observe the binding of three chemically diverse ligand molecules: antagonist tiotropium (TTP), partial agonist arecoline (ARc) and full agonist acetylcholine (ACh). In comparison with earlier microsecond-timescale conventional MD simulations, aMD greatly accelerated the binding of ACh to the receptor orthosteric ligand-binding site and the binding of TTP to an extracellular vestibule. Further aMD simulations also captured binding of ARc to the receptor orthosteric site. Additionally, all three ligands were observed to bind in the extracellular vestibule during their binding pathways, suggesting that it is a metastable binding site. This study demonstrates the applicability of aMD to protein-ligand binding, especially the drug recognition of GPCRs.

Molecular cloning and functional characterization of the apple sucrose transporter gene MdSUT2.

PubMed

Ma, Qi-Jun; Sun, Mei-Hong; Liu, Ya-Jing; Lu, Jing; Hu, Da-Gang; Hao, Yu-Jin

2016-12-01

Sucrose is not only the primary photosynthetic product but also the major component translocated in the phloem of economically important plant species. Sucrose transporters or carriers (SUTs or SUCs), function as sucrose/H + symporters and play a crucial role in determining the cell-to-cell distribution of sucrose throughout the entire plant. However, whether such genes are involved in responses to abiotic stress and other biological processes is largely unknown. Here, we report that MdSUT2 in apple is a homolog of the Arabidopsis vacuolar sucrose transporter AtSUT2. Ectopic expression of MdSUT2 in Arabidopsis decreased sucrose sensitivity in germination and seeding stage and increased sucrose transport activity. In addition, our results showed that MdSUT2 impacted on plant growth by accelerating vegetative growth and promoting early flowering in Arabidopsis. Overexpression of MdSUT2 significantly improved abiotic stress tolerance including NaCl, ABA, and mannitol in apple calli and Arabidopsis. Together, these findings provide evidence that the apple sucrose transporter MdSUT2 is involved in abiotic stress resistance and the regulation of plant growth and development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

An apple MYB transcription factor, MdMYB3, is involved in regulation of anthocyanin biosynthesis and flower development

PubMed Central

2013-01-01

Background Red coloration of fruit is an important trait in apple, and it is mainly attributed to the accumulation of anthocyanins, a class of plant flavonoid metabolites. Anthocyanin biosynthesis is genetically determined by structural and regulatory genes. Plant tissue pigmentation patterns are mainly controlled by expression profiles of regulatory genes. Among these regulatory genes are MYB transcription factors (TFs), wherein the class of two-repeats (R2R3) is deemed the largest, and these are associated with the anthocyanin biosynthesis pathway. Although three MdMYB genes, almost identical in nucleotide sequences, have been identified in apple, it is likely that there are other R2R3 MYB TFs that are present in the apple genome that are also involved in the regulation of coloration of red color pigmentation of the skin of apple fruits. Results In this study, a novel R2R3 MYB gene has been isolated and characterized in apple. This MYB gene is closely related to the Arabidopsis thaliana AtMYB3, and has been designated as MdMYB3. This TF belongs to the subgroup 4 R2R3 family of plant MYB transcription factors. This apple MdMYB3 gene is mapped onto linkage group 15 of the integrated apple genetic map. Transcripts of MdMYB3 are detected in all analyzed tissues including leaves, flowers, and fruits. However, transcripts of MdMYB3 are higher in excocarp of red-skinned apple cultivars than that in yellowish-green skinned apple cultivars. When this gene is ectopically expressed in Nicotiana tabacum cv. Petite Havana SR1, flowers of transgenic tobacco lines carrying MdMYB3 have exhibited increased pigmentation and accumulate higher levels of anthocyanins and flavonols than wild-type flowers. Overexpression of MdMYB3 has resulted in transcriptional activation of several flavonoid pathway genes, including CHS, CHI, UFGT, and FLS. Moreover, peduncles of flowers and styles of pistils of transgenic plants overexpressing MdMYB3 are longer than those of wild-type plants, thus suggesting that this TF is involved in regulation of flower development. Conclusions This study has identified a novel MYB transcription factor in the apple genome. This TF, designated as MdMYB3, is involved in transcriptional activation of several flavonoid pathway genes. Moreover, this TF not only regulates the accumulation of anthocyanin in the skin of apple fruits, but it is also involved in the regulation of flower development, particularly that of pistil development. PMID:24199943

An apple MYB transcription factor, MdMYB3, is involved in regulation of anthocyanin biosynthesis and flower development.

PubMed

Vimolmangkang, Sornkanok; Han, Yuepeng; Wei, Guochao; Korban, Schuyler S

2013-11-07

Red coloration of fruit is an important trait in apple, and it is mainly attributed to the accumulation of anthocyanins, a class of plant flavonoid metabolites. Anthocyanin biosynthesis is genetically determined by structural and regulatory genes. Plant tissue pigmentation patterns are mainly controlled by expression profiles of regulatory genes. Among these regulatory genes are MYB transcription factors (TFs), wherein the class of two-repeats (R2R3) is deemed the largest, and these are associated with the anthocyanin biosynthesis pathway. Although three MdMYB genes, almost identical in nucleotide sequences, have been identified in apple, it is likely that there are other R2R3 MYB TFs that are present in the apple genome that are also involved in the regulation of coloration of red color pigmentation of the skin of apple fruits. In this study, a novel R2R3 MYB gene has been isolated and characterized in apple. This MYB gene is closely related to the Arabidopsis thaliana AtMYB3, and has been designated as MdMYB3. This TF belongs to the subgroup 4 R2R3 family of plant MYB transcription factors. This apple MdMYB3 gene is mapped onto linkage group 15 of the integrated apple genetic map. Transcripts of MdMYB3 are detected in all analyzed tissues including leaves, flowers, and fruits. However, transcripts of MdMYB3 are higher in excocarp of red-skinned apple cultivars than that in yellowish-green skinned apple cultivars. When this gene is ectopically expressed in Nicotiana tabacum cv. Petite Havana SR1, flowers of transgenic tobacco lines carrying MdMYB3 have exhibited increased pigmentation and accumulate higher levels of anthocyanins and flavonols than wild-type flowers. Overexpression of MdMYB3 has resulted in transcriptional activation of several flavonoid pathway genes, including CHS, CHI, UFGT, and FLS. Moreover, peduncles of flowers and styles of pistils of transgenic plants overexpressing MdMYB3 are longer than those of wild-type plants, thus suggesting that this TF is involved in regulation of flower development. This study has identified a novel MYB transcription factor in the apple genome. This TF, designated as MdMYB3, is involved in transcriptional activation of several flavonoid pathway genes. Moreover, this TF not only regulates the accumulation of anthocyanin in the skin of apple fruits, but it is also involved in the regulation of flower development, particularly that of pistil development.

76 FR 30878 - Lowering Miners' Exposure to Respirable Coal Mine Dust, Including Continuous Personal Dust Monitors

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... Eastern Daylight Saving Time on June 20, 2011. ADDRESSES: Comments must be identified with ``RIN 1219-AB64... commenters additional time to review and comment on the proposed rule. DATES: The comment period for the... providing additional time for interested parties to submit comments. MSHA is extending the comment period...

The relationship of deiodinase 1 genotype and thyroid function to lifetime history of major depression in three independent populations.

PubMed

Philibert, Robert A; Beach, Steven R H; Gunter, Tracy D; Todorov, Alexandre A; Brody, Gene H; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-07-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1,555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime MD and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone, free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3'UTR of DIO1 (rs11206244), were associated with altered FT4 levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. Copyright © 2011 Wiley-Liss, Inc.

Spin-diffusions and diffusive molecular dynamics

NASA Astrophysics Data System (ADS)

Farmer, Brittan; Luskin, Mitchell; Plecháč, Petr; Simpson, Gideon

2017-12-01

Metastable configurations in condensed matter typically fluctuate about local energy minima at the femtosecond time scale before transitioning between local minima after nanoseconds or microseconds. This vast scale separation limits the applicability of classical molecular dynamics (MD) methods and has spurned the development of a host of approximate algorithms. One recently proposed method is diffusive MD which aims at integrating a system of ordinary differential equations describing the likelihood of occupancy by one of two species, in the case of a binary alloy, while quasistatically evolving the locations of the atoms. While diffusive MD has shown itself to be efficient and provide agreement with observations, it is fundamentally a model, with unclear connections to classical MD. In this work, we formulate a spin-diffusion stochastic process and show how it can be connected to diffusive MD. The spin-diffusion model couples a classical overdamped Langevin equation to a kinetic Monte Carlo model for exchange amongst the species of a binary alloy. Under suitable assumptions and approximations, spin-diffusion can be shown to lead to diffusive MD type models. The key assumptions and approximations include a well-defined time scale separation, a choice of spin-exchange rates, a low temperature approximation, and a mean field type approximation. We derive several models from different assumptions and show their relationship to diffusive MD. Differences and similarities amongst the models are explored in a simple test problem.

Common genetic variation and novel loci associated with volumetric mammographic density.

PubMed

Brand, Judith S; Humphreys, Keith; Li, Jingmei; Karlsson, Robert; Hall, Per; Czene, Kamila

2018-04-17

Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h 2 SNP ]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P < 5 × 10 - 8 ): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h 2 SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h 2 SNP to previously observed narrow-sense h 2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h 2 SNP /h 2 ratios varying between dense and nondense MD components.

Failure to launch: the self-regulating Md-MYB10 R6 gene from apple is active in flowers but not leaves of Petunia.

PubMed

Boase, Murray R; Brendolise, Cyril; Wang, Lei; Ngo, Hahn; Espley, Richard V; Hellens, Roger P; Schwinn, Kathy E; Davies, Kevin M; Albert, Nick W

2015-10-01

The Md - MYB10 R6 gene from apple is capable of self-regulating in heterologous host species and enhancing anthocyanin pigmentation, but the activity of MYB10 is dependent on endogenous protein partners. Coloured foliage due to anthocyanin pigments (bronze/red/black) is an attractive trait that is often lacking in many bedding, ornamental and horticultural plants. Apples (Malus × domestica) containing an allelic variant of the anthocyanin regulator, Md-MYB10 R6 , are highly pigmented throughout the plant, due to autoregulation by MYB10 upon its own promoter. We investigated whether Md-MYB10 R6 from apple is capable of functioning within the heterologous host Petunia hybrida to generate plants with novel pigmentation patterns. The Md-MYB10 R6 transgene (MYB10-R6 pro :MYB10:MYB10 term ) activated anthocyanin synthesis when transiently expressed in Antirrhinum rosea (dorsea) petals and petunia leaf discs. Stable transgenic petunias containing Md-MYB10 R6 lacked foliar pigmentation but had coloured flowers, complementing the an2 phenotype of 'Mitchell' petunia. The absence of foliar pigmentation was due to the failure of the Md-MYB10 R6 gene to self-activate in vegetative tissues, suggesting that additional protein partners are required for Md-MYB10 to activate target genes in this heterologous system. In petunia flowers, where endogenous components including MYB-bHLH-WDR (MBW) proteins were present, expression of the Md-MYB10 R6 promoter was initiated, allowing auto-regulation to occur and activating anthocyanin production. Md-MYB10 is capable of operating within the petunia MBW gene regulation network that controls the expression of the anthocyanin biosynthesis genes, AN1 (bHLH) and MYBx (R3-MYB repressor) in petals.

Comparison of outpatient and home-based exercise training programmes for COPD: A systematic review and meta-analysis.

PubMed

Wuytack, Francesca; Devane, Declan; Stovold, Elizabeth; McDonnell, Melissa; Casey, Michelle; McDonnell, Timothy J; Gillespie, Paddy; Raymakers, Adam; Lacasse, Yves; McCarthy, Bernard

2018-03-01

Chronic obstructive pulmonary disease is a common, preventable and treatable disease. Exercise training programmes (ETPs) improve symptoms, health-related quality of life (HRQoL) and exercise capacity, but the optimal setting is unknown. In this review, we compared the effects of ETPs in different settings on HRQoL and exercise capacity. We searched (5 July 2016) the Cochrane Airways Group Specialised Register, ClinicalTrials.gov and World Health Organization trials portal. We selected studies, extracted data and assessed risk of bias with two independent reviewers. We calculated mean differences (MD) with 95% CI. We assessed the quality of evidence using Grades of Recommendation, Assessment, Development and Evaluation. Ten trials (934 participants) were included. Hospital (outpatient) and home-based ETPs (seven trials) were equally effective at improving HRQoL on the Chronic Respiratory Questionnaire (CRQ) (dyspnoea: MD -0.09, 95% CI: -0.28 to 0.10; fatigue: MD -0.00, 95% CI: -0.18 to 0.17; emotional: MD 0.10, 95% CI: -0.24 to 0.45; and mastery: MD -0.02, 95% CI: -0.28 to 0.25; moderate quality) and on the St George's Respiratory Questionnaire (SGRQ) (MD -0.82, 95% CI: -7.47 to 5.83, low quality). Hospital (outpatient) and community-based ETPs (three trials) were equally effective at improving HRQoL (CRQ dyspnoea: MD 0.29, 95% CI: -0.05 to 0.62, moderate quality; fatigue: MD -0.02, 95% CI: -1.09 to 1.05, low quality; emotional: MD 0.10, 95% CI: -0.40 to 0.59, moderate quality; and mastery: MD -0.08, 95% CI: -0.45 to 0.28, moderate quality). There was no difference in exercise capacity. There was low to moderate evidence that outpatient and home-based ETPs are equally effective. See related Editorial. © 2017 Asian Pacific Society of Respirology.

Molecular cloning and functional analysis of a UV-B photoreceptor gene, MdUVR8 (UV Resistance Locus 8), from apple.

PubMed

Zhao, Cheng; Mao, Ke; You, Chun-Xiang; Zhao, Xian-Yan; Wang, Shu-Hui; Li, Yuan-Yuan; Hao, Yu-Jin

2016-06-01

UVR8 (UV Resistance Locus 8) is an ultraviolet-B (UV-B; 280-315nm) light receptor that is involved in regulating many aspects of plant growth and development. UV-B irradiation can increase the development of flower and fruit coloration in many fruit trees, such as grape, pear and apple. Previous investigations of the structure and functions of UVR8 in plants have largely focused on Arabidopsis. Here, we isolated the UVR8 gene from apple (Malus domestica) and analyzed its function in transgenic Arabidopsis. Genomic and protein sequence analysis showed that MdUVR8 shares high similarity with the AtUVR8 protein from Arabidopsis, including the conserved seven-bladed β-propeller, the C27 region, the 3 "GWRHT" motifs and crucial amino-acid residues (14 Trps, 2 Args). A point mutation prediction and three-dimensional structural analysis of MdUVR8 indicated that it has a similar structure to AtUVR8 and that the crucial residues are also important in MdUVR8. In terms of transcript levels, MdUVR8 expression was up-regulated by UV-B light, which suggests that its expression follows a 24-h circadian rhythm. Using heterologous expression of MdUVR8 in both uvr8-1 mutant and wild-type (WT) Arabidopsis, we found that MdUVR8 regulates hypocotyl elongation and gene expression under UV-B light. These data provide functional evidence for a role of MdUVR8 in controlling photomorphogenesis under UV-B light and indicate that the function of UVR8 is conserved between Arabidopsis and apple. Furthermore, we examined the interaction between MdUVR8 and MdCOP1 (constitutive photomorphogenic1) using a yeast two-hybrid assay and a co-immunoprecipitation assay. This interaction provides a direction for investigating the regulatory mechanisms of the UV-B-light pathway in apple. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Summary of the 2016 Partners Against Mortality in Epilepsy (PAME) Conference.

PubMed

2016-01-01

Authors: Kevin D Graber, MD, Jeffrey Buchhalter, MD, PhD, Elson So, MD, Rainer Surges, MD, Detlev Boison, PhD, Franck Kalume, PhD, Cyndi Wright, Brian Gehlbach, MD, Jeff Noebels, MD, PhD, Vicky Whittemore, PhD, Elizabeth J. Donner, MD, MSc, Tom Stanton, MPP, Henry Smithson, MD, Jane Hanna, Masud Seyal, MD, PhD, Philippe Ryvlin, MD, PhD The third biannual Partners Against Mortality in Epilepsy (PAME) conference was held in Alexandria, VA from June 23-26, 2016. This was an intimate meeting of clinical and basic scientists, clinicians, people affected by Sudden Unexpected Death in Epilepsy Patients (SUDEP) in a loved one, people living with epilepsy and patient advocate organizations. Plenary sessions have been summarized by moderators, including: 1) Mortality in people with epilepsy: epidemiology and surveillance. 2) Mortality in children. 3) What do we know about the factors that predispose certain people to die from a seizure? 4) What are the events that occur during and after a seizure that cause a death in SUDEP? 5) What are the options for prevention now and in the future? 6) Advocacy perspectives: how can we speed up awareness and prevention? 7) Updates and discussion on select programs in mortality research. Breakout sessions allowed for a more focused audience. Those summarized here are: Frequent non-SUDEP causes of mortality in people with epilepsy; Mechanisms of SUDEP; Lessons learned in grief and how to better support families; Future directions for research to impact prevention; and How do we improve SUDEP risk disclosure? While significant progress has been made with review of human mortality in epilepsy and study of animal models, this meeting emphasized the need for: better understandings of the epidemiology of SUDEP, advances in the understandings of mechanisms, continued search for biomarkers and preventative measures, patient education, increased awareness, continued advocacy for patient and family support and research funding.

77 FR 4054 - Extension of Agency Information Collection Activity Under OMB Review: TSA Customer Comment Card

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-26

... Information Collection Activity Under OMB Review: TSA Customer Comment Card AGENCY: Transportation Security...). TSA uses a customer comment card to collect passenger comments at airports, including complaints... other forms of information technology. Information Collection Requirement Title: TSA Customer Comment...

Joint analyses of open comments and quantitative data: Added value in a job satisfaction survey of hospital professionals.

PubMed

Gilles, Ingrid; Mayer, Mauro; Courvoisier, Nelly; Peytremann-Bridevaux, Isabelle

2017-01-01

To obtain a comprehensive understanding of the job opinions of hospital professionals by conducting qualitative analyses of the open comments included in a job satisfaction survey and combining these results with the quantitative results. A cross-sectional survey targeting all Lausanne University Hospital professionals was performed in the fall of 2013. The survey considered ten job satisfaction dimensions (e.g. self-fulfilment, workload, management, work-related burnout, organisational commitment, intent to stay) and included an open comment section. Computer-assisted qualitative analyses were conducted on these comments. Satisfaction rates on the included dimensions and professional groups were entered as predictive variables in the qualitative analyses. Of 10 838 hospital professionals, 4978 participated in the survey and 1067 provided open comments. Data from 1045 respondents with usable comments constituted the analytic sample (133 physicians, 393 nurses, 135 laboratory technicians, 247 administrative staff, including researchers, 67 logistic staff, 44 psycho-social workers, and 26 unspecified). Almost a third of the comments addressed scheduling issues, mostly related to problems and exhaustion linked to shifts, work-life balance, and difficulties with colleagues' absences and the consequences for quality of care and patient safety. The other two-thirds related to classic themes included in job satisfaction surveys. Although some comments were provided equally by all professional groups, others were group specific: work and hierarchy pressures for physicians, healthcare quality and patient safety for nurses, skill recognition for administrative staff. Overall, respondents' comments were consistent with their job satisfaction ratings. Open comment analysis provides a comprehensive understanding of hospital professionals' job experiences, allowing better consideration of quality initiatives that match the needs of professionals with reality.

Joint analyses of open comments and quantitative data: Added value in a job satisfaction survey of hospital professionals

PubMed Central

Gilles, Ingrid; Mayer, Mauro; Courvoisier, Nelly; Peytremann-Bridevaux, Isabelle

2017-01-01

Objective To obtain a comprehensive understanding of the job opinions of hospital professionals by conducting qualitative analyses of the open comments included in a job satisfaction survey and combining these results with the quantitative results. Design A cross-sectional survey targeting all Lausanne University Hospital professionals was performed in the fall of 2013. Material and methods The survey considered ten job satisfaction dimensions (e.g. self-fulfilment, workload, management, work-related burnout, organisational commitment, intent to stay) and included an open comment section. Computer-assisted qualitative analyses were conducted on these comments. Satisfaction rates on the included dimensions and professional groups were entered as predictive variables in the qualitative analyses. Participants Of 10 838 hospital professionals, 4978 participated in the survey and 1067 provided open comments. Data from 1045 respondents with usable comments constituted the analytic sample (133 physicians, 393 nurses, 135 laboratory technicians, 247 administrative staff, including researchers, 67 logistic staff, 44 psycho-social workers, and 26 unspecified). Results Almost a third of the comments addressed scheduling issues, mostly related to problems and exhaustion linked to shifts, work-life balance, and difficulties with colleagues’ absences and the consequences for quality of care and patient safety. The other two-thirds related to classic themes included in job satisfaction surveys. Although some comments were provided equally by all professional groups, others were group specific: work and hierarchy pressures for physicians, healthcare quality and patient safety for nurses, skill recognition for administrative staff. Overall, respondents’ comments were consistent with their job satisfaction ratings. Conclusion Open comment analysis provides a comprehensive understanding of hospital professionals’ job experiences, allowing better consideration of quality initiatives that match the needs of professionals with reality. PMID:28296974

EIS No. 20100312 EIS Comanche Peak Nuclear Power Plant Units 3 and 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bjornstad, David J

2010-08-01

In accordance with Section 309(a) of the Clean Air Act, EPA is required to make its comments on EISs issued by other Federal agencies public. Historically, EPA has met this mandate by publishing weekly notices of availability of EPA comments, which includes a brief summary of EPA's comment letters, in the Federal Register. Since February 2008, EPA has been including its comment letters on EISs on its Web site at: http://www.epa.gov/compliance/nepa/eisdata.html. Including the entire EIS comment letters on the Web site satisfies the Section 309(a) requirement to make EPA's comments on EISs available to the public. Accordingly, on March 31,more » 2010, EPA discontinued the publication of the notice of availability of EPA comments in the Federal Register. EIS No. 20100312, Draft EIS, NRC, TX, Comanche Peak Nuclear Power Plant Units 3 and 4, Application for Combined Licenses (COLs) for Construction Permits and Operating Licenses, (NUREG-1943), Hood and Somervell Counties, TX, Comment Period Ends: 10/26/2010.« less

The Maastricht-Duke bridge: An era of mentoring in clinical research - A model for mentoring in clinical research - A tribute to Dr. Galen Wagner.

PubMed

Meijs, Loek; Zusterzeel, Robbert; Wellens, Hein Jj; Gorgels, Anton Pm

With the passing of Dr. Galen Wagner, an exceptional collaboration between Maastricht University Medical Center, The Netherlands, and Duke Clinical Research Institute, USA, has come to an end. This article focuses on the background of what Galen coined the Maastricht-Duke bridge (MD-bridge), its merits, limitations and development throughout the years, and his special role. Between 2004 and 2015, 23 Maastricht University medical students and post-graduate students were enrolled in the 4-month research elective, mentored by Galen and the Maastricht co-mentor. They were asked to complete a survey about their MD-bridge experience. Sixteen out of the 23 students responded. None but 1 participant had prior research experience. Following their MD bridge-program most participants published 1 or more manuscripts and/or presented their research in an international setting. They felt they had full responsibility as a leader of their project with all participants developing meaningful skills useful in their current job. Fourteen out of 16 would recommend the MD-bridge experience to others. Participants considered the program of great value for their personal growth and independence, giving a feeling of achievement. In addition, for some participants it led to careers in foreign countries including medical practice and research, or obtaining PhDs. With Galen's impressive career of mentoring students, including the 23 MD-bridge participants, he has left behind an amazing concept of self-development in research and personal life. The successes of the MD-bridge prove that it is possible for students to be young investigators during or just after medical school with the potential to contribute to developing meaningful skills and noteworthy careers. Collaborations between international universities, such as the MD-bridge, are feasible and should be embraced by other institutions. Published by Elsevier Inc.

Sex-dependent effects of neonatal maternal deprivation on endocannabinoid levels in the adipose tissue: influence of diet.

PubMed

Mela, Virginia; Piscitelli, Fabiana; Berzal, Alvaro Llorente; Chowen, Julie; Silvestri, Cristoforo; Viveros, Maria Paz; Di Marzo, Vincenzo

2016-08-01

Maternal deprivation (MD) during neonatal life has diverse long-term effects, including modification of metabolism. We have previously reported that MD modifies the metabolic response to high-fat diet (HFD) intake, with this response being different between males and females, while previous studies indicate that in mice with HFD-induced obesity, endocannabinoid (EC) levels are markedly altered in various brown and white adipose tissue depots. Here, we analyzed the effects of MD (24 h at postnatal day 9), alone or in combination with a HFD from weaning until the end of the experiment in Wistar rats of both sexes. Brown and white perirenal and subcutaneous adipose tissues were collected and the levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) were determined. In males, MD increased the content of OEA in brown and 2-AG in subcutaneous adipose tissues, while in females the content of 2-AG was increased in perirenal fat. Moreover, in females, MD decreased AEA and OEA levels in perirenal and subcutaneous adipose tissues, respectively. HFD decreased the content of 2-AG in brown fat of both sexes and OEA in brown and subcutaneous adipose tissue of control females. In contrast, in subcutaneous fat, HFD increased AEA levels in MD males and OEA levels in control and MD males. The present results show for the first time that MD and HFD induce sex-dependent effects on the main ECs, AEA, and 2-AG, and of AEA-related mediators, OEA and PEA, in the rat brown and white (visceral and subcutaneous) adipose tissues.

Fast recovery of free energy landscapes via diffusion-map-directed molecular dynamics.

PubMed

Preto, Jordane; Clementi, Cecilia

2014-09-28

The reaction pathways characterizing macromolecular systems of biological interest are associated with high free energy barriers. Resorting to the standard all-atom molecular dynamics (MD) to explore such critical regions may be inappropriate as the time needed to observe the relevant transitions can be remarkably long. In this paper, we present a new method called Extended Diffusion-Map-directed Molecular Dynamics (extended DM-d-MD) used to enhance the sampling of MD trajectories in such a way as to rapidly cover all important regions of the free energy landscape including deep metastable states and critical transition paths. Moreover, extended DM-d-MD was combined with a reweighting scheme enabling to save on-the-fly information about the Boltzmann distribution. Our algorithm was successfully applied to two systems, alanine dipeptide and alanine-12. Due to the enhanced sampling, the Boltzmann distribution is recovered much faster than in plain MD simulations. For alanine dipeptide, we report a speedup of one order of magnitude with respect to plain MD simulations. For alanine-12, our algorithm allows us to highlight all important unfolded basins in several days of computation when one single misfolded event is barely observable within the same amount of computational time by plain MD simulations. Our method is reaction coordinate free, shows little dependence on the a priori knowledge of the system, and can be implemented in such a way that the biased steps are not computationally expensive with respect to MD simulations thus making our approach well adapted for larger complex systems from which little information is known.

Lipid droplet-associated gene expression and chromatin remodelling in LIPASE 5'-upstream region from beginning- to mid-endodormant bud in 'Fuji' apple.

PubMed

Saito, Takanori; Wang, Shanshan; Ohkawa, Katsuya; Ohara, Hitoshi; Ikeura, Hiromi; Ogawa, Yukiharu; Kondo, Satoru

2017-11-01

We found that lipid accumulation in the meristem region and the expression of MdLIP2A, which appears to be regulated by chromatin remodeling, coincided with endodormancy induction in the 'Fuji' apple. In deciduous trees, including apples (Malus × domestica Borkh.), lipid accumulation in the meristem region towards endodormancy induction has been thought to be an important process for the acquisition of cold tolerance. In this study, we conducted histological staining of crude lipids in the meristem region of 'Fuji' apples and found that lipid accumulation coincided with endodormancy induction. Since a major component of lipid bodies (triacylglycerol) is esterified fatty acids, we analysed fatty acid-derived volatile compounds and genes encoding fatty acid-modifying enzymes (MdLOX1A and MdHPL2A); the reduction of lipid breakdown also coincided with endodormancy induction. We then characterised the expression patterns of lipid body-regulatory genes MdOLE1 and MdLIP2A during endodormancy induction and found that the expression of MdLIP2A correlated well with lipid accumulation towards endodormancy induction. Based on these results, we conducted chromatin remodelling studies and localized the cis-element in the 5'-upstream region of MdLIP2A to clarify its regulatory mechanism. Finally, we revealed that chromatin was concentrated - 764 to - 862 bp of the 5'-upstream region of MdLIP2A, which harbours the GARE [gibberellin responsive MYB transcription factor binding site] and CArG [MADS-box transcription factor binding site] motifs-meristem development-related protein-binding sites.

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

PubMed

Bower, Joseph; Fast, Douglas; Garofolo, Fabio; Gouty, Dominique; Hayes, Roger; Lowes, Steve; Nicholson, Robert; LeLacheur, Richard; Bravo, Jennifer; Shoup, Ronald; Dumont, Isabelle; Carbone, Mary; Zimmer, Jennifer; Ortuno, Jordi; Caturla, Maria Cruz; Datin, Jim; Lansing, Tim; Fatmi, Saadya; Struwe, Petra; Sheldon, Curtis; Islam, Rafiqul; Yu, Mathilde; Hulse, Jim; Kamerud, John; Lin, John; Doughty, John; Kurylak, Kai; Tang, Daniel; Buonarati, Mike; Blanchette, Alexandre; Levesque, Ann; Gagnon-Carignan, Sofi; Lin, Jenny; Ray, Gene; Liu, Yanseng; Khan, Masood; Xu, Allan; El-Sulayman, Gibran; DiMarco, Chantal; Bouhajib, Mohammed; Tacey, Dick; Jenkins, Rand; der Strate, Barry van; Briscoe, Chad; Karnik, Shane; Rhyne, Paul; Garofolo, Wei; Schultz, Gary; Roberts, Andrew; Redrup, Mike; DuBey, Ira; Conliffe, Phyllis; Pekol, Teri; Hantash, Jamil; Cojocaru, Laura; Allen, Mike; Reuschel, Scott; Watson, Andrea; Farrell, Colin; Groeber, Elizabeth; Malone, Michele; Nowatzke, William; Fang, Xinping

2014-01-01

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.

Very virulent plus strains of MDV induce acute form of transient paralysis in both susceptible and resistant chicken lines

USDA-ARS?s Scientific Manuscript database

Marek’s Disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, crippling, weight loss, and transient paralysis (TP). TP is a disease of the central nervous system...

Medical Device Plug-and-Play Interoperability Standards and Technology Leadership

DTIC Science & Technology

2012-10-01

External Network Pump Adapter PulseOx Adapter • MD MP3 cart is a platform for the development of smart pump control algorithms • It includes...delivery with bounded latency Medical Device Mobile PnP Prototype Platform (MD MP3 ) • Got MDCF code to run on the BeagleBoard development boards we are

Mathematics Difficulty with and without Reading Difficulty: Findings and Implications from a Four-Year Longitudinal Study

ERIC Educational Resources Information Center

Vukovic, Rose K.

2012-01-01

An overarching question guided this study:What is mathematics difficulty (MD) independent of reading difficulty (RD)? The sample included 203 children whom the researchers followed from kindergarten to third grade. The researchers used latent growth modeling to investigate the relationship between MD and measures of working memory, short-term…

78 FR 56222 - Agency Information Collection Activities; Comment Request; Highly Qualified Teachers Clearance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-12

..., commercial delivery, or hand delivery. Please note that comments submitted by fax or email and those submitted after the comment period will not be accepted. Written requests for information or comments... respondents, including through the use of information technology. Please note that written comments received...

78 FR 18576 - Agency Information Collection Activities; Comment Request; Experimental Sites Data Collection...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... delivery, or hand delivery. Please note that comments submitted by fax or email and those submitted after the comment period will not be accepted. Written requests for information or comments submitted by... respondents, including through the use of information technology. Please note that written comments received...

Screening probiotic candidates for a mixture of probiotics to enhance the growth performance, immunity, and disease resistance of Asian seabass, Lates calcarifer (Bloch), against Aeromonas hydrophila.

PubMed

Lin, Hsueh-Li; Shiu, Ya-Li; Chiu, Chiu-Shia; Huang, Shih-Ling; Liu, Chun-Hung

2017-01-01

Six bacteria, including, Lactobacillus casei M15, Lac. plantarum D8, Lac. pentosus BD6, Lac. fermentum LW2, Enterococcus faecium 10-10, and Bacillus subtilis E20, and one yeast, Saccharomyces cerevisiae P13 were selected as probiotics for Asian seabass, Lates calcarifer, by tracking the growth performance and disease resistance of fish against Aeromonas hydrophila in the first trial. The probiotic efficiency screening results showed that B. subtilis E20 and Lac. pentosus BD6, and S. cerevisiae P13 and Lac. fermentum LW2 respectively improved either the growth performance or disease resistance. Therefore, these four probiotics were then selected to prepare a probiotics mixture, and this was incorporated in equal proportions into diets for Asian seabass at levels of 0 (control), and 10 6 (MD6), 10 7 (MD7), 10 8 (MD8), and 10 9 (MD9) colony-forming units (cfu) (kg diet) -1 . A synergistic effect of the combined probiotics was investigated in this study, and the probiotics mixture was able to improve both the growth performance and health status of fish. After 56 days of feeding, fish fed the MD9 diet had a higher final weight and percentage of weight gain. In addition, protein contents in the dorsal muscle of fish fed the MD8 and MD9 diets were significantly higher compared to the control. For the pathogen challenge test, fish fed the MD7, MD8, and MD9 diets had significantly lower cumulative mortalities after A. hydrophila infection compared to those of fish fed the control and MD6 diets, which might have been due to increased respiratory bursts, decreased superoxide dismutase activity in leucocytes, and increased phagocytic activity. Therefore, we considered that the probiotics mixture could adequately provide probiotic efficiency for Asian seabass, and the diet containing 10 9  cfu (kg diet) -1 probiotic mixture is recommended to improve the growth and health status of Asian seabass. Copyright © 2016. Published by Elsevier Ltd.

High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM.

PubMed

Pedraza-Flechas, Ana María; Lope, Virginia; Sánchez-Contador, Carmen; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Moreo, Pilar; Ederra, María; Miranda-García, Josefa; Vidal, Carmen; Llobet, Rafael; Aragonés, Nuria; Salas-Trejo, Dolores; Pollán, Marina; Pérez-Gómez, Beatriz

2017-06-01

Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women. Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables. Results: Having ever worked in NSW was not associated with MD [Formula: see text]:0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD >15 years :20.7% vs. MD never :16.5%;[Formula: see text]:1.25; 95% CI,1.01-1.54). This association was mainly observed in postmenopausal participants ([Formula: see text]:1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with ≤2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week ([Formula: see text]:1.42; 95% CI, 1.10-1.84). Conclusions: Performing NSW was associated with higher MD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies. Impact: Our findings suggest that MD could play a role in the pathway between long-term NSW and breast cancer. Cancer Epidemiol Biomarkers Prev; 26(6); 905-13. ©2017 AACR . ©2017 American Association for Cancer Research.

Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal Cortex and Mediodorsal Thalamus

PubMed Central

Ouhaz, Zakaria; Fleming, Hugo; Mitchell, Anna S.

2018-01-01

The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move), the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction and cognitive functioning) that are associated with many different neuropsychiatric disorders. In particular, we will focus here on the cognitive symptoms of schizophrenia and suggest testable hypotheses about how changes to MD-frontal cortex interactions may affect cognitive processes in this disorder. PMID:29467603

78 FR 34708 - Proposed Information Collection (Foot (Including Flatfeet (pes planus)) Conditions Disability...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-10

... (Including Flatfeet (pes planus)) Conditions Disability Benefits Questionnaire) Activity: Comment Request...)) Conditions Disability Benefits Questionnaire)'' in any correspondence. During the comment period, comments...)) Conditions Disability Benefits Questionnaire), VA Form 21-0960M-6. OMB Control Number: 2900--NEW (Foot...

Adherence to the Mediterranean diet and risk of lung cancer in the Netherlands Cohort Study.

PubMed

Schulpen, Maya; van den Brandt, Piet A

2018-03-01

The evidence on a cancer-protective effect of the Mediterranean diet (MD) is still limited. Therefore, we investigated the association between MD adherence and lung cancer risk. Data were used from 120 852 participants of the Netherlands Cohort Study (NLCS), aged 55-69 years. Dietary habits were assessed at baseline (1986) using a validated FFQ and alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol, were calculated. After 20·3 years of follow-up, 2861 lung cancer cases and 3720 subcohort members (case-cohort design) could be included in multivariable Cox regression analyses. High (6-8) v. low (0-3) aMED excluding alcohol was associated with non-significantly reduced lung cancer risks in men and women with hazard ratios of 0·91 (95 % CI 0·72, 1·15) and 0·73 (95 % CI 0·49, 1·09), respectively. aMED-containing models generally fitted better than mMED-containing models. In never smokers, a borderline significant decreasing trend in lung cancer risk was observed with increasing aMED excluding alcohol. Analyses stratified by the histological lung cancer subtypes did not identify subtypes with a particularly strong inverse relation with MD adherence. Generally, the performance of aMED and World Cancer Research Fund/American Institute for Cancer Research dietary score variants without alcohol was comparable. In conclusion, MD adherence was non-significantly inversely associated with lung cancer risk in the NLCS. Future studies should focus on differences in associations across the sexes and histological subtypes. Furthermore, exclusion of alcohol from MD scores should be investigated more extensively, primarily with respect to a potential role of the MD in cancer prevention.

The Malus domestica sugar transporter gene family: identifications based on genome and expression profiling related to the accumulation of fruit sugars

PubMed Central

Wei, Xiaoyu; Liu, Fengli; Chen, Cheng; Ma, Fengwang; Li, Mingjun

2014-01-01

In plants, sugar transporters are involved not only in long-distance transport, but also in sugar accumulations in sink cells. To identify members of sugar transporter gene families and to analyze their function in fruit sugar accumulation, we conducted a phylogenetic analysis of the Malus domestica genome. Expression profiling was performed with shoot tips, mature leaves, and developed fruit of “Gala” apple. Genes for sugar alcohol [including 17 sorbitol transporters (SOTs)], sucrose, and monosaccharide transporters, plus SWEET genes, were selected as candidates in 31, 9, 50, and 27 loci, respectively, of the genome. The monosaccharide transporter family appears to include five subfamilies (30 MdHTs, 8 MdEDR6s, 5 MdTMTs, 3 MdvGTs, and 4 MdpGLTs). Phylogenetic analysis of the protein sequences indicated that orthologs exist among Malus, Vitis, and Arabidopsis. Investigations of transcripts revealed that 68 candidate transporters are expressed in apple, albeit to different extents. Here, we discuss their possible roles based on the relationship between their levels of expression and sugar concentrations. The high accumulation of fructose in apple fruit is possibly linked to the coordination and cooperation between MdTMT1/2 and MdEDR6. By contrast, these fruits show low MdSWEET4.1 expression and a high flux of fructose produced from sorbitol. Our study provides an exhaustive survey of sugar transporter genes and demonstrates that sugar transporter gene families in M. domestica are comparable to those in other species. Expression profiling of these transporters will likely contribute to improving our understanding of their physiological functions in fruit formation and the development of sweetness properties. PMID:25414708

The Malus domestica sugar transporter gene family: identifications based on genome and expression profiling related to the accumulation of fruit sugars.

PubMed

Wei, Xiaoyu; Liu, Fengli; Chen, Cheng; Ma, Fengwang; Li, Mingjun

2014-01-01

In plants, sugar transporters are involved not only in long-distance transport, but also in sugar accumulations in sink cells. To identify members of sugar transporter gene families and to analyze their function in fruit sugar accumulation, we conducted a phylogenetic analysis of the Malus domestica genome. Expression profiling was performed with shoot tips, mature leaves, and developed fruit of "Gala" apple. Genes for sugar alcohol [including 17 sorbitol transporters (SOTs)], sucrose, and monosaccharide transporters, plus SWEET genes, were selected as candidates in 31, 9, 50, and 27 loci, respectively, of the genome. The monosaccharide transporter family appears to include five subfamilies (30 MdHTs, 8 MdEDR6s, 5 MdTMTs, 3 MdvGTs, and 4 MdpGLTs). Phylogenetic analysis of the protein sequences indicated that orthologs exist among Malus, Vitis, and Arabidopsis. Investigations of transcripts revealed that 68 candidate transporters are expressed in apple, albeit to different extents. Here, we discuss their possible roles based on the relationship between their levels of expression and sugar concentrations. The high accumulation of fructose in apple fruit is possibly linked to the coordination and cooperation between MdTMT1/2 and MdEDR6. By contrast, these fruits show low MdSWEET4.1 expression and a high flux of fructose produced from sorbitol. Our study provides an exhaustive survey of sugar transporter genes and demonstrates that sugar transporter gene families in M. domestica are comparable to those in other species. Expression profiling of these transporters will likely contribute to improving our understanding of their physiological functions in fruit formation and the development of sweetness properties.

Solution NMR Refinement of a Metal Ion Bound Protein Using Metal Ion Inclusive Restrained Molecular Dynamics Methods

PubMed Central

Chakravorty, Dhruva K.; Wang, Bing; Lee, Chul Won; Guerra, Alfredo J.; Giedroc, David P.; Merz, Kenneth M.

2013-01-01

Correctly calculating the structure of metal coordination sites in a protein during the process of nuclear magnetic resonance (NMR) structure determination and refinement continues to be a challenging task. In this study, we present an accurate and convenient means by which to include metal ions in the NMR structure determination process using molecular dynamics (MD) constrained by NMR-derived data to obtain a realistic and physically viable description of the metal binding site(s). This method provides the framework to accurately portray the metal ions and its binding residues in a pseudo-bond or dummy-cation like approach, and is validated by quantum mechanical/molecular mechanical (QM/MM) MD calculations constrained by NMR-derived data. To illustrate this approach, we refine the zinc coordination complex structure of the zinc sensing transcriptional repressor protein Staphylococcus aureus CzrA, generating over 130 ns of MD and QM/MM MD NMR-data compliant sampling. In addition to refining the first coordination shell structure of the Zn(II) ion, this protocol benefits from being performed in a periodically replicated solvation environment including long-range electrostatics. We determine that unrestrained (not based on NMR data) MD simulations correlated to the NMR data in a time-averaged ensemble. The accurate solution structure ensemble of the metal-bound protein accurately describes the role of conformational dynamics in allosteric regulation of DNA binding by zinc and serves to validate our previous unrestrained MD simulations of CzrA. This methodology has potentially broad applicability in the structure determination of metal ion bound proteins, protein folding and metal template protein-design studies. PMID:23609042

Atmospheric Pressure and Onset of Episodes of Menière’s Disease - A Repeated Measures Study

PubMed Central

Strobl, Ralf; Heinlin, Nina; Krause, Eike; Olzowy, Bernhard; Koppe, Christina; Grill, Eva

2016-01-01

Background External changes of air pressure are transmitted to the middle and inner ear and may be used therapeutically in Menière’s disease, one of the most common vertigo disorders. We analyzed the possible relationship of atmospheric pressure and other meteorological parameters with the onset of MD vertigo episodes in order to determine whether atmospheric pressure changes play a role in the occurrence of MD episodes. Methods Patients of a tertiary outpatient dizziness clinic diagnosed with MD were asked to keep a daily vertigo diary to document MD episodes (2004–2009). Local air pressure, absolute temperature and dew point temperature were acquired on an hourly basis. Change in meteorological parameters was conceptualized as the maximum difference in a 24 hour time frame preceding each day. Effects were estimated using additive mixed models with a random participant effect. We included lagged air parameters, age, sex, weekday and season in the model. Results A total of 56 persons (59% female) with mean age 54 years were included. Mean follow-up time was 267 days. Persons experienced on average 10.3 episodes during the observation period (median 8). Age and change in air pressure were significantly associated with vertigo onset risk (Odds Ratio = 0.979 and 1.010). We could not show an effect of sex, weekday, season, air temperature, and dew point temperature. Conclusions Change in air pressure was significantly associated with onset of MD episodes, suggesting a potential triggering mechanism in the inner ear. MD patients may possibly use air pressure changes as an early warning system for vertigo attacks in the future. PMID:27096752

78 FR 26345 - Brookfield Renewable Power, Inc.; Notice of Application Accepted for Filing, Soliciting Comments...

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Evaluation of self-reported work ability and usefulness of interventions among sick-listed patients.

PubMed

Wåhlin, Charlotte; Ekberg, Kerstin; Persson, Jan; Bernfort, Lars; Öberg, Birgitta

2013-03-01

To describe the types of intervention offered, to investigate the relationship between the type of intervention given, patient-reported usefulness of interventions and the effect on self-reported work ability in a cohort of sick-listed patients with musculoskeletal disorders (MSD) or mental disorders (MD). A prospective cohort study was performed including 810 newly sick-listed patients (MSD 62 % and MD 38 %). The baseline questionnaire included sociodemographic characteristics and measures of work ability. The 3-month follow-up questionnaire included measures of work ability, type of intervention received, and judgment of usefulness. Twenty-five percent received medical intervention modalities (MI) only, 45 % received a combination of medical and rehabilitative intervention modalities (CRI) and 31 % received work-related interventions combined with medical or rehabilitative intervention modalities (WI). Behavioural treatments were more common for patients with MD compared with MSD and exercise therapy were more common for patients with MSD. The most prevalent workplace interventions were adjustment of work tasks or the work environment. Among patients with MD, WI was found to be useful and improved work ability significantly more compared with only MI or CRI. For patients with MSD, no significant differences in improved work ability were found between interventions. Patients with MD who received a combination of work-related and clinical interventions reported best usefulness and best improvement in work ability. There was no difference in improvements in work ability between rehabilitation methods in the MSD group. There seems to be a gap between scientific evidence and praxis behaviour in the rehabilitation process. Unimodal rehabilitation was widely applied in the early rehabilitation process, a multimodal treatment approach was rare and only one-third received work-related interventions. It remains a challenge to understand who needs what type of intervention.

Tackling the conformational sampling of larger flexible compounds and macrocycles in pharmacology and drug discovery.

PubMed

Chen, I-Jen; Foloppe, Nicolas

2013-12-15

Computational conformational sampling underpins much of molecular modeling and design in pharmaceutical work. The sampling of smaller drug-like compounds has been an active area of research. However, few studies have tested in details the sampling of larger more flexible compounds, which are also relevant to drug discovery, including therapeutic peptides, macrocycles, and inhibitors of protein-protein interactions. Here, we investigate extensively mainstream conformational sampling methods on three carefully curated compound sets, namely the 'Drug-like', larger 'Flexible', and 'Macrocycle' compounds. These test molecules are chemically diverse with reliable X-ray protein-bound bioactive structures. The compared sampling methods include Stochastic Search and the recent LowModeMD from MOE, all the low-mode based approaches from MacroModel, and MD/LLMOD recently developed for macrocycles. In addition to default settings, key parameters of the sampling protocols were explored. The performance of the computational protocols was assessed via (i) the reproduction of the X-ray bioactive structures, (ii) the size, coverage and diversity of the output conformational ensembles, (iii) the compactness/extendedness of the conformers, and (iv) the ability to locate the global energy minimum. The influence of the stochastic nature of the searches on the results was also examined. Much better results were obtained by adopting search parameters enhanced over the default settings, while maintaining computational tractability. In MOE, the recent LowModeMD emerged as the method of choice. Mixed torsional/low-mode from MacroModel performed as well as LowModeMD, and MD/LLMOD performed well for macrocycles. The low-mode based approaches yielded very encouraging results with the flexible and macrocycle sets. Thus, one can productively tackle the computational conformational search of larger flexible compounds for drug discovery, including macrocycles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Complexity analysis of spontaneous brain activity in mood disorders: A magnetoencephalography study of bipolar disorder and major depression.

PubMed

Fernández, Alberto; Al-Timemy, Ali H; Ferre, Francisco; Rubio, Gabriel; Escudero, Javier

2018-04-26

The lack of a biomarker for Bipolar Disorder (BD) causes problems in the differential diagnosis with other mood disorders such as major depression (MD), and misdiagnosis frequently occurs. Bearing this in mind, we investigated non-linear magnetoencephalography (MEG) patterns in BD and MD. Lempel-Ziv Complexity (LZC) was used to evaluate the resting-state MEG activity in a cross-sectional sample of 60 subjects, including 20 patients with MD, 16 patients with BD type-I, and 24 control (CON) subjects. Particular attention was paid to the role of age. The results were aggregated by scalp region. Overall, MD patients showed significantly higher LZC scores than BD patients and CONs. Linear regression analyses demonstrated distinct tendencies of complexity progression as a function of age, with BD patients showing a divergent tendency as compared with MD and CON groups. Logistic regressions confirmed such distinct relationship with age, which allowed the classification of diagnostic groups. The patterns of neural complexity in BD and MD showed not only quantitative differences in their non-linear MEG characteristics but also divergent trajectories of progression as a function of age. Moreover, neural complexity patterns in BD patients resembled those previously observed in schizophrenia, thus supporting preceding evidence of common neuropathological processes. Copyright © 2018 Elsevier Inc. All rights reserved.

The mediating effect of Mediterranean diet on the relation between smoking and colorectal cancer: a case-control study.

PubMed

Kontou, Niki; Psaltopoulou, Theodora; Soupos, Nick; Polychronopoulos, Evangelos; Xinopoulos, Dimitrios; Linos, Athena; Panagiotakos, Demosthenes B

2013-10-01

The protective role of Mediterranean diet (MD) and the detrimental effect of smoking on colorectal cancer (CRC) have already been shown. The aim of this work was to evaluate the potential mediating effect of MD on the association between the aforementioned factor (smoking) and CRC. It is a case-control study. Two hundred fifty consecutive patients with CRC (63 ± 12 years, 59% males) and 250 age-sex group-matched controls, both from the area of Attica, were studied. Various socio-demographic, clinical, lifestyle (including detailed smoking habits) and dietary characteristics were measured. Adherence to the MD was evaluated using the MedDietScore (theoretical range 0-55). Each unit increase in the MedDietScore was associated with 13% lower likelihood of CRC (P < 0.001). Smoking habits were associated with 2.9-fold the likelihood of CRC among participants who were away from the MD (i.e. MedDietScore < 29) and with 2.1-fold the likelihood of CRC among those who were close to the MD (P < 0.05). Adherence to the MD was associated with a less detrimental association of smoking habits with CRC, suggesting indirect benefits of adherence to this dietary pattern with regards to CRC morbidity and mortality.

Comparison of Video Head Impulse Test and Caloric Reflex Test in advanced unilateral definite Menière's disease.

PubMed

Rubin, F; Simon, F; Verillaud, B; Herman, P; Kania, R; Hautefort, C

2018-06-01

There have been very few studies of the Video Head Impulse Test (VHIT) in patients with Menière's Disease (MD). Some reported 100% normal VHIT results, others not. These discrepancies may be due to differences in severity. The present study compared VHIT and caloric reflex test results in advanced unilateral definite MD. A prospective study included 37 consecutive patients, with a mean age of 56±12 years. Mean hearing loss was 59±18dB HL; 12 patients were subject to Tumarkin's otolithic crises. Abnormal caloric reflex was defined as ≥20% deficit, and abnormal VHIT as presence of saccades or <0.64 gain in vertical semicircular canals and <0.78 in horizontal canals. All patients had normal VHIT results, and 3 had normal caloric reflex; mean caloric reflex deficit was 45%. The present study is the only one to use the August 2015 updated definition of MD. The results showed that, outside of episodes of crisis, VHIT was normal during advanced unilateral definite MD, in contrast to abnormal caloric reflex. This feature could help distinguish MD from other inner ear diseases, and it would be interesting to try to confirm this hypothesis by studying MD patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Contribution of Equal-Sign Instruction beyond Word-Problem Tutoring for Third-Grade Students with Mathematics Difficulty.

PubMed

Powell, Sarah R; Fuchs, Lynn S

2010-05-01

Elementary school students often misinterpret the equal sign (=) as an operational rather than a relational symbol. Such misunderstanding is problematic because solving equations with missing numbers may be important for higher-order mathematics skills including word problems. Research indicates equal-sign instruction can alter how typically-developing students use the equal sign, but no study has examined effects for students with mathematics difficulty (MD) or how equal-sign instruction contributes to word-problem skill for students with or without MD. The present study assessed the efficacy of equal-sign instruction within word-problem tutoring. Third-grade students with MD (n = 80) were assigned to word-problem tutoring, word-problem tutoring plus equal-sign instruction (combined) tutoring, or no-tutoring control. Combined tutoring produced better improvement on equal sign tasks and open equations compared to the other 2 conditions. On certain forms of word problems, combined tutoring but not word-problem tutoring alone produced better improvement than control. When compared at posttest to 3(rd)-grade students without MD on equal sign tasks and open equations, only combined tutoring students with MD performed comparably.

Molecular dynamics simulations and novel drug discovery.

PubMed

Liu, Xuewei; Shi, Danfeng; Zhou, Shuangyan; Liu, Hongli; Liu, Huanxiang; Yao, Xiaojun

2018-01-01

Molecular dynamics (MD) simulations can provide not only plentiful dynamical structural information on biomacromolecules but also a wealth of energetic information about protein and ligand interactions. Such information is very important to understanding the structure-function relationship of the target and the essence of protein-ligand interactions and to guiding the drug discovery and design process. Thus, MD simulations have been applied widely and successfully in each step of modern drug discovery. Areas covered: In this review, the authors review the applications of MD simulations in novel drug discovery, including the pathogenic mechanisms of amyloidosis diseases, virtual screening and the interaction mechanisms between drugs and targets. Expert opinion: MD simulations have been used widely in investigating the pathogenic mechanisms of diseases caused by protein misfolding, in virtual screening, and in investigating drug resistance mechanisms caused by mutations of the target. These issues are very difficult to solve by experimental methods alone. Thus, in the future, MD simulations will have wider application with the further improvement of computational capacity and the development of better sampling methods and more accurate force fields together with more efficient analysis methods.

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis

PubMed Central

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4–15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: −18.05, 95% CI (−25.51, −10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (−32.80, −14.18), P < 0.00001], 7day [MD: −33.01, 95% CI (−37.31, −28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: −1.91, 95% CI (−2.06, −1.75), P < 0.00001], as well as the duration of phototherapy [MD: −0.64, 95% CI (−0.84, −0.44), P < 0.00001] and hospitalization [MD: −2.68, 95% CI (−3.18, −2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported. Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice. PMID:28713275

Probiotics Supplementation Therapy for Pathological Neonatal Jaundice: A Systematic Review and Meta-Analysis.

PubMed

Chen, Zhe; Zhang, Lingli; Zeng, Linan; Yang, Xiaoyan; Jiang, Lucan; Gui, Ge; Zhang, Zuojie

2017-01-01

Background: Neonatal jaundice is a relatively prevalent disease and affects approximately 2.4-15% newborns. Probiotics supplementation therapy could assist to improve the recovery of neonatal jaundice, through enhancing immunity mainly by regulating bacterial colonies. However, there is limited evidence regarding the effect of probiotics on bilirubin level in neonates. Therefore, this study aims at systematically evaluating the efficacy and safety of probiotics supplement therapy for pathological neonatal jaundice. Methods: Databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) were searched and the deadline is December 2016. Randomized controlled trials (RCTs) of probiotics supplementation for pathological neonatal jaundice in publications were extracted by two reviewers. The cochrane tool was applied to assessing the risk of bias of the trials. The extracted information of RCTs should include efficacy rate, serum total bilirubin level, time of jaundice fading, duration of phototherapy, duration of hospitalization, adverse reactions. The main outcomes of the trials were analyzed by Review Manager 5.3 software. The relative risks (RR) or mean difference (MD) with a 95% confidence interval (CI) was used to measure the effect. Results: 13 RCTs involving 1067 neonatal with jaundice were included in the meta-analysis. Probiotics supplementation treatment showed efficacy [RR: 1.19, 95% CI (1.12, 1.26), P < 0.00001] in neonatal jaundice. It not only decreased the total serum bilirubin level after 3day [MD: -18.05, 95% CI (-25.51, -10.58), P < 0.00001], 5day [MD: -23.49, 95% CI (-32.80, -14.18), P < 0.00001], 7day [MD: -33.01, 95% CI (-37.31, -28.70), P < 0.00001] treatment, but also decreased time of jaundice fading [MD: -1.91, 95% CI (-2.06, -1.75), P < 0.00001], as well as the duration of phototherapy [MD: -0.64, 95% CI (-0.84, -0.44), P < 0.00001] and hospitalization [MD: -2.68, 95% CI (-3.18, -2.17), P < 0.00001], when compared with the control group. Additionally, no serious adverse reaction was reported. Conclusion: This meta-analysis shows that probiotics supplementation therapy is an effective and safe treatment for pathological neonatal jaundice.

Concurrent aerobic plus resistance exercise versus aerobic exercise alone to improve health outcomes in paediatric obesity: a systematic review and meta-analysis.

PubMed

García-Hermoso, Antonio; Ramírez-Vélez, Robinson; Ramírez-Campillo, Rodrigo; Peterson, Mark D; Martínez-Vizcaíno, Vicente

2018-02-01

To determine if the combination of aerobic and resistance exercise is superior to aerobic exercise alone for the health of obese children and adolescents. Systematic review with meta-analysis. Computerised search of 3 databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry). Studies that compared the effect of supervised concurrent exercise versus aerobic exercise interventions, with anthropometric and metabolic outcomes in paediatric obesity (6-18 years old). The mean differences (MD) of the parameters from preintervention to postintervention between groups were pooled using a random-effects model. 12 trials with 555 youths were included in the meta-analysis. Compared with aerobic exercise alone, concurrent exercise resulted in greater reductions in body mass (MD=-2.28 kg), fat mass (MD=-3.49%; and MD=-4.34 kg) and low-density lipoprotein cholesterol (MD=-10.20 mg/dL); as well as greater increases in lean body mass (MD=2.20 kg) and adiponectin level (MD=2.59 μg/mL). Differences were larger for longer term programmes (>24 weeks). Concurrent aerobic plus resistance exercise improves body composition, metabolic profiles, and inflammatory state in the obese paediatric population. CRD42016039807. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Associative learning and regional white matter deficits in mild cognitive impairment.

PubMed

Boespflug, Erin L; Eliassen, James; Welge, Jeffrey; Krikorian, Robert

2014-01-01

While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration. Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements. DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks. Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI, TS MD and DA were inversely associated with associative learning but not list learning. In addition to supporting prior evidence implicating the fornix in early AD pathology, these data implicate a profile of neurodegeneration associated with early MCI. Further, they suggest that associative learning tasks are more sensitive to early neurodegeneration and may be useful in identifying individuals at risk for AD.

Application of Polychromatic µCT for Mineral Density Determination

PubMed Central

Zou, W.; Hunter, N.; Swain, M.V.

2011-01-01

Accurate assessment of mineral density (MD) provides information critical to the understanding of mineralization processes of calcified tissues, including bones and teeth. High-resolution three-dimensional assessment of the MD of teeth has been demonstrated by relatively inaccessible synchrotron radiation microcomputed tomography (SRµCT). While conventional desktop µCT (CµCT) technology is widely available, polychromatic source and cone-shaped beam geometry confound MD assessment. Recently, considerable attention has been given to optimizing quantitative data from CµCT systems with polychromatic x-ray sources. In this review, we focus on the approaches that minimize inaccuracies arising from beam hardening, in particular, beam filtration during the scan, beam-hardening correction during reconstruction, and mineral density calibration. Filtration along with lowest possible source voltage results in a narrow and near-single-peak spectrum, favoring high contrast and minimal beam-hardening artifacts. More effective beam monochromatization approaches are described. We also examine the significance of beam-hardening correction in determining the accuracy of mineral density estimation. In addition, standards for the calibration of reconstructed grey-scale attenuation values against MD, including K2PHO4 liquid phantom, and polymer-hydroxyapatite (HA) and solid hydroxyapatite (HA) phantoms, are discussed. PMID:20858779

Shorter sleep duration and better sleep quality are associated with greater tissue density in the brain.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Shinada, Takamitsu; Sakaki, Kohei; Nozawa, Takayuki; Ikeda, Shigeyuki; Yokota, Susumu; Daniele, Magistro; Sassa, Yuko; Kawashima, Ryuta

2018-04-11

Poor sleep quality is associated with unfavorable psychological measurements, whereas sleep duration has complex relationships with such measurements. The aim of this study was to identify the associations between microstructural properties of the brain and sleep duration/sleep quality in a young adult. The associations between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and sleep duration/sleep quality were investigated in a study cohort of 1201 normal young adults. Positive correlations between sleep duration and MD of widespread areas of the brain, including the prefrontal cortex (PFC) and the dopaminergic systems, were identified. Negative correlations between sleep quality and MD of the widespread areas of the brain, including the PFC and the right hippocampus, were also detected. Lower MD has been previously associated with more neural tissues in the brain. Further, shorter sleep duration was associated with greater persistence and executive functioning (lower Stroop interference), whereas good sleep quality was associated with states and traits relevant to positive affects. These results suggest that bad sleep quality and longer sleep duration were associated with aberrant neurocognitive measurements in the brain in healthy young adults.

David Kasner, MD, and the Road to Pars Plana Vitrectomy

PubMed Central

Blodi, Christopher F.

2016-01-01

David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.

PubMed

Mallik, Atul K; Drzezga, Alexander; Minoshima, Satoshi

2017-01-01

Precision medicine (PM) has been defined as "prevention and treatment strategies that take individual variability into account." Molecular imaging (MI) is an ideally suited tool for PM approaches to neurodegenerative dementia and movement disorders (MD). Here we review PM approaches and discuss how they may be applied to other associated neurodegenerative dementia and MD. With ongoing major therapeutic research initiatives that include the use of molecular imaging, we look forward to established interventions targeted to specific molecular pathophysiology and expect the potential benefit of MI PM approaches in neurodegenerative dementia and MD will only increase. Copyright © 2016 Elsevier Inc. All rights reserved.

Li-Doped Ionic Liquid Electrolytes: From Bulk Phase to Interfacial Behavior

NASA Technical Reports Server (NTRS)

Haskins, Justin B.; Lawson, John W.

2016-01-01

Ionic liquids have been proposed as candidate electrolytes for high-energy density, rechargeable batteries. We present an extensive computational analysis supported by experimental comparisons of the bulk and interfacial properties of a representative set of these electrolytes as a function of Li-salt doping. We begin by investigating the bulk electrolyte using quantum chemistry and ab initio molecular dynamics to elucidate the solvation structure of Li(+). MD simulations using the polarizable force field of Borodin and coworkers were then performed, from which we obtain an array of thermodynamic and transport properties. Excellent agreement is found with experiments for diffusion, ionic conductivity, and viscosity. Combining MD simulations with electronic structure computations, we computed the electrochemical window of the electrolytes across a range of Li(+)-doping levels and comment on the role of the liquid environment. Finally, we performed a suite of simulations of these Li-doped electrolytes at ideal electrified interfaces to evaluate the differential capacitance and the equilibrium Li(+) distribution in the double layer. The magnitude of differential capacitance is in good agreement with our experiments and exhibits the characteristic camel-shaped profile. In addition, the simulations reveal Li(+) to be highly localized to the second molecular layer of the double layer, which is supported by additional computations that find this layer to be a free energy minimum with respect to Li(+) translation.

Variations in Patterns of Utilization and Charges for the Care of Headache in North Carolina, 2000-2009: A Statewide Claims' Data Analysis.

PubMed

Hurwitz, Eric L; Vassilaki, Maria; Li, Dongmei; Schneider, Michael J; Stevans, Joel M; Phillips, Reed B; Phelan, Shawn P; Lewis, Eugene A; Armstrong, Richard C

2016-05-01

The purpose of the study was to compare patterns of utilization and charges generated by medical doctors (MDs), doctors of chiropractic (DCs), and physical therapists (PTs) for the treatment of headache in North Carolina. Retrospective analysis of claims data from the North Carolina State Health Plan for Teachers and State Employees from 2000 to 2009. Data were extracted from Blue Cross Blue Shield of North Carolina for the North Carolina State Health Plan using International Classification of Diseases, Ninth Revision, diagnostic codes for headache. The claims were separated by individual provider type, combination of provider types, and referral patterns. The majority of patients and claims were in the MD-only or MD plus referral patterns. Chiropractic patterns represented less than 10% of patients. Care patterns with single-provider types and no referrals incurred the least charges on average for headache. When care did not include referral providers or services, MD with DC care was generally less expensive than MD care with PT. However, when combined with referral care, MD care with PT was generally less expensive. Compared with MD-only care, risk-adjusted charges (available 2006-2009) for patients in the middle risk quintile were significantly less for DC-only care. Utilization and expenditures for headache treatment increased from 2000 to 2009 across all provider groups. MD care represented the majority of total allowed charges in this study. MD care and DC care, alone or in combination, were overall the least expensive patterns of headache care. Risk-adjusted charges were significantly less for DC-only care. Copyright © 2016 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

Identification of two metallothionein genes and their roles in stress responses of Musca domestica toward hyperthermy and cadmium tolerance.

PubMed

Tang, Ting; Huang, Da-wei; Zhang, Di; Wu, Yin-jian; Murphy, Robert W; Liu, Feng-song

2011-10-01

Stress proteins such as metallothioneins (MTs) play a key role in cellular protection against environmental stressors. In nature, insects such as houseflies (Musca domestica) are commonly exposed to multiple stressors including heavy metals (e.g. Cadmium, Cd) and high temperatures. In this paper, we identify two novel MT genes from the cDNAs of M. domestica, MdMT1 and MdMT2, which putatively encode 40 and 42 amino acid residues respectively. Expression of the two MTs' mRNAs, which are examined in the fat body, gut, hemocyte, and the epidermis. From our study, we saw that the expression of MdMT1 and MdMT2 are enhanced by Cd and thermal stress. Levels of expression are highest at 10 mM Cd(2+) within a 24-h period, and expressions increase significantly with exposure to 10 mM Cd for 12h. Levels of the mRNAs are up-regulated after heat shock and that of MdMT2 reaches its maximum peak faster than MdMT1. Both of the MT genes might be involved in a transient systemic tolerance response to stressors and they may play important roles in heavy metal and high temperature tolerance in the housefly. To detect whether or not the MTs bind heavy metals, the target genes are cloned into the prokaryotic expression vector pET-DsbA to obtain fusion protein expressed in Escherichia coli BL21 (DE3). Recombinant DsbA-MdMT1 significantly increases tolerance of the host bacteria to Cd(2+), but DsbA-MdMT2 is absent. These differential characteristics will facilitate future investigations into the physiological functions of MTs. Copyright © 2011 Elsevier Inc. All rights reserved.

A Pilot Study: Dietary Energy Density is Similar between Active Women with and without Exercise-Associated Menstrual Dysfunction

PubMed Central

Hand, Taryn M.; Howe, Stephanie; Cialdella-Kam, Lynn; Hoffman, Charlotte P. Guebels; Manore, Melinda

2016-01-01

Low energy availability (EA) (e.g., insufficient energy intake (EI) to match energy needs, including exercise energy expenditure) has been identified as a primary contributor to exercise-associated menstrual dysfunction (ExMD) in active women. For health reasons, active women may self-select diets lower in energy density (ED, kcal/g), which can inadvertently contribute to inadequate EI. Using data from two studies, we compared the ED of active women with ExMD (n = 9; 24 ± 6 years) to eumenorrheic (EU) active controls (EU: n = 18, 27 ± 6 years). ED was calculated from 6 to 7 days weighted food records using two methods: with/without beverages. ANOVA and Wilcoxon Rank-Sum were used to test group differences. ED was not different between groups, but there was a trend toward a lower median ED (10%) (p = 0.049 unadjusted; p = 0.098 adjusted) in the ExMD-group (Method 1—all beverages: ExMD = 1.01 kcal/g (range = 0.52–1.41), EU = 1.22 kcal/g (range = 0.72–1.72); Method 2—without beverages: ExMD = 1.51 kcal/g (range = 1.26–2.06), EU = 1.69 kcal/g (range = 1.42–2.54)). This lower ED represents a 9% decrease (~219 kcal/day) in EI (ExMD = 2237 ± 378 kcal/day; EU = 2456 ± 470 kcal/day; p > 0.05). EI and macro/micronutrient intakes were similar for groups. In the ExMD-group, low ED could contribute to lower EI and EA. Future research should examine the interaction of ED and exercise on appetite, EI, and EA in active women, especially those with ExMD. PMID:27104560

Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

NASA Technical Reports Server (NTRS)

Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

Decreased serum L-arginine and L-citrulline levels in major depression.

PubMed

Hess, S; Baker, G; Gyenes, G; Tsuyuki, R; Newman, S; Le Melledo, Jean-Michel

2017-11-01

It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 μmol/L and 84.89 + 25.16, p = 0.04 μmol/L and L-citrulline 31.58 + 6.05 μmol/L and 35.19 + 6.85 μmol/L, p = 0.03, respectively). The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

A 24-week randomised controlled trial comparing usual care and metabolic-based diet plans in obese adults.

PubMed

McDoniel, S O; Hammond, R S

2010-10-01

Usual care (UC) practice for weight management often includes providing standardised, ad libitum, low-calorie nutrition plans. However, weight loss using such plans appears comparable with metabolic-based diet (MD) plans that are closer to resting energy expenditure (REE) level. In addition, MD plans are approximately 250-750 kcal/day higher in caloric values compared with UC plans. Therefore, the purpose of this study was to compare weight loss and eating behaviour differences between UC and MD plans. Seventy-four obese (30.0-51.7 kg/m(2) ) adults (21-67 years) voluntarily participated in a 24-week randomised study. UC men and women received a fixed, ad libitum, 1600 and 1200 kcal/day nutrient plan, respectively. MD participants received an individualised treatment plan based from measured REE. Bodyweight and eating behaviours (i.e. intake, restraint and uncontrolled eating) were assessed over time. Intent-to-treat analysis indicated no significant difference in weight loss (UC: -5.7 ± 6.3% vs. MD: -5.3 ± 7.1% p = 0.67) between groups over time. There was no difference in daily energy intake (UC: 2490 ± 576 kcal/day vs. MD: 2525 ± 475 kcal/day) at 24 weeks between groups. Both groups experienced a significant improvement (p < 0.05) in eating dietary restraint and uncontrolled eating yet there was no difference between groups. From this study, UC calorie plans do not generate more weight loss or improve eating behaviours in comparison with MD calorie plans. As treatment effects are comparable, clinicians can select UC or MD plan options based on clinician and patient preference. © 2010 Blackwell Publishing Ltd.

Different Preclimacteric Events in Apple Cultivars with Modified Ripening Physiology

PubMed Central

Singh, Vikram; Weksler, Asya; Friedman, Haya

2017-01-01

“Anna” is an early season apple cultivar exhibiting a fast softening and juiciness loss during storage, in comparison to two mid-late season cultivars “Galaxy” and “GD.” The poor storage capacity of “Anna” was correlated with high lipid oxidation-related autoluminescence, high respiration and ethylene production rates, associated with high expression of MdACO1, 2, 4, 7, and MdACS1. All cultivars at harvest responded to exogenous ethylene by enhancing ethylene production, typical of system-II. The contribution of pre-climacteric events to the poor storage capacity of “Anna” was examined by comparing respiration and ethylene production rates, response to exogenous ethylene, expression of genes responsible for ethylene biosynthesis and response, and developmental regulators in the three cultivars throughout fruit development. In contrast to the “Galaxy” and “GD,” “Anna” showed higher ethylene production and respiration rates during fruit development, and exhibited auto-stimulatory (system II-like) effect in response to exogenous ethylene. The higher ethylene production rate in “Anna” was correlated with higher expression of ethylene biosynthesis genes, MdACS3a MdACO2, 4, and 7 during early fruit development. The expression of negative regulators of ripening (AP2/ERF) and ethylene response pathway, (MdETR1,2 and MdCTR1) was lower in “Anna” in comparison to the other two cultivars throughout development and ripening. Similar pattern of gene expression was found for SQUAMOSA promoter binding protein (SBP)-box genes, including MdCNR and for MdFUL. Taken together, this study provides new understanding on pre-climacteric events in “Anna” that might affect its ripening behavior and physiology following storage. PMID:28928755

Biochemical characterisation of MdCXE1, a carboxylesterase from apple that is expressed during fruit ripening.

PubMed

Souleyre, Edwige J F; Marshall, Sean D G; Oakeshott, John G; Russell, Robyn J; Plummer, Kim M; Newcomb, Richard D

2011-05-01

Esters are an important component of apple (Malus×domestica) flavour. Their biosynthesis increases in response to the ripening hormone ethylene, but their metabolism by carboxylesterases (CXEs) is poorly understood. We have identified 16 members of the CXE multigene family from the commercial apple cultivar, 'Royal Gala', that contain all the conserved features associated with CXE members of the α/β hydrolase fold superfamily. The expression of two genes, MdCXE1 and MdCXE16 was characterised in an apple fruit development series and in a transgenic line of 'Royal Gala' (AO3) that is unable to synthesise ethylene in fruit. In wild-type MdCXE1 is expressed at low levels during early stages of fruit development, rising to a peak of expression in apple fruit at harvest maturity. It is not significantly up-regulated by ethylene in the skin of AO3 fruit. MdCXE16 is expressed constitutively in wild-type throughout fruit development, and is up-regulated by ethylene in skin of AO3 fruit. Semi-purified recombinant MdCXE1 was able to hydrolyse a range of 4-methyl umbelliferyl ester substrates that included those containing acyl moieties that are found in esters produced by apple fruit. Kinetic characterisation of MdCXE1 revealed that the enzyme could be inhibited by organophosphates and that its ability to hydrolyse esters showed increasing affinity (K(m)) but decreasing turnover (k(cat)) as substrate acyl carbon length increases from C2 to C16. Our results suggest that MdCXE1 may have an impact on apple flavour through its ability to hydrolyse relevant flavour esters in ripe apple fruit. Copyright © 2011 Elsevier Ltd. All rights reserved.

Muscular Dystrophy (MD)

MedlinePlus

... may include physical therapy, respiratory therapy, speech therapy, orthopedic appliances used for support, and corrective orthopedic surgery. Drug therapy includes corticosteroids to slow muscle ...

A Molecular Dynamics Simulation of the Turbulent Couette Minimal Flow Unit

NASA Astrophysics Data System (ADS)

Smith, Edward

2016-11-01

What happens to turbulent motions below the Kolmogorov length scale? In order to explore this question, a 300 million molecule Molecular Dynamics (MD) simulation is presented for the minimal Couette channel in which turbulence can be sustained. The regeneration cycle and turbulent statistics show excellent agreement to continuum based computational fluid dynamics (CFD) at Re=400. As MD requires only Newton's laws and a form of inter-molecular potential, it captures a much greater range of phenomena without requiring the assumptions of Newton's law of viscosity, thermodynamic equilibrium, fluid isotropy or the limitation of grid resolution. The fundamental nature of MD means it is uniquely placed to explore the nature of turbulent transport. A number of unique insights from MD are presented, including energy budgets, sub-grid turbulent energy spectra, probability density functions, Lagrangian statistics and fluid wall interactions. EPSRC Post Doctoral Prize Fellowship.

Ab initio ONIOM-molecular dynamics (MD) study on the deamination reaction by cytidine deaminase.

PubMed

Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

2007-08-23

We applied the ONIOM-molecular dynamics (MD) method to the hydrolytic deamination of cytidine by cytidine deaminase, which is an essential step of the activation process of the anticancer drug inside the human body. The direct MD simulations were performed for the realistic model of cytidine deaminase by calculating the energy and its gradient by the ab initio ONIOM method on the fly. The ONIOM-MD calculations including the thermal motion show that the neighboring amino acid residue is an important factor of the environmental effects and significantly affects not only the geometry and energy of the substrate trapped in the pocket of the active site but also the elementary step of the catalytic reaction. We successfully simulate the second half of the catalytic cycle, which has been considered to involve the rate-determining step, and reveal that the rate-determining step is the release of the NH3 molecule.

Pyrite: A blender plugin for visualizing molecular dynamics simulations using industry-standard rendering techniques.

PubMed

Rajendiran, Nivedita; Durrant, Jacob D

2018-05-05

Molecular dynamics (MD) simulations provide critical insights into many biological mechanisms. Programs such as VMD, Chimera, and PyMOL can produce impressive simulation visualizations, but they lack many advanced rendering algorithms common in the film and video-game industries. In contrast, the modeling program Blender includes such algorithms but cannot import MD-simulation data. MD trajectories often require many gigabytes of memory/disk space, complicating Blender import. We present Pyrite, a Blender plugin that overcomes these limitations. Pyrite allows researchers to visualize MD simulations within Blender, with full access to Blender's cutting-edge rendering techniques. We expect Pyrite-generated images to appeal to students and non-specialists alike. A copy of the plugin is available at http://durrantlab.com/pyrite/, released under the terms of the GNU General Public License Version 3. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Role of Molecular Dynamics and Related Methods in Drug Discovery.

PubMed

De Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, Andrea

2016-05-12

Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.

Effects of Obesity and Leptin Deficiency on Morphine Pharmacokinetics in a Mouse Model.

PubMed

Dalesio, Nicholas M; Hendrix, Craig W; McMichael, Douglas Hale; Thompson, Carol B; Lee, Carlton K K; Pho, Huy; Arias, Rafael S; Lynn, Rachael Rzasa; Galinkin, Jeffrey; Yaster, Myron; Brown, Robert H; Schwartz, Alan R

2016-12-01

Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy. WT mice received several dosing regimens of morphine. Obese mice (30 g) received one 80 mg/kg bolus of morphine. Blood was collected at fixed times after morphine injection for quantification of plasma morphine and morphine 3-glucuronide (M3G) levels. PK parameters used to evaluate morphine metabolism included area-under the curve (AUC150), maximal morphine concentration (CMAX), and M3G-to-morphine ratio, and drug elimination was determined by clearance (Cl/F), volume of distribution, and half-life (T1/2). PK parameters were compared between mouse groups by the use of 1-way analysis of variance, with P values less than .05 considered significant. DIO compared with WT mice had significantly decreased morphine metabolism with lower M3G-to-morphine ratio (mean difference [MD]: -4.9; 95% confidence interval [CI]: -8.8 to -0.9) as well as a decreased Cl/F (MD: -4.0; 95% CI: -8.9 to -0.03) Ob/ob compared with WT mice had a large increase in morphine exposure with a greater AUC150 (MD: 980.4; 95% CI: 630.1-1330.6), CMAX (MD: 6.8; 95% CI: 2.7-10.9), and longer T1/2 (MD: 23.1; 95% CI: 10.5-35.6), as well as a decreased Cl/F (MD: -7.0; 95% CI: -11.6 to -2.7). Several PK parameters were significantly greater in ob/ob compared with DIO mice, including AUC150 (MD: 636.4; 95% CI: 207.4-1065.4), CMAX (MD: 5.3; 95% CI: 3.2-10.3), and T1/2 (MD: 18.3; 95% CI: 2.8-33.7). When leptin was replaced in ob/ob mice, PK parameters began to approach DIO and WT levels. LR compared with ob/ob mice had significant decreases in AUC150 (MD: -779.9; 95% CI: -1229.8 to -330), CMAX (MD: -6.1; 95% CI: -11.4 to -0.9), and T1/2 (MD: -19; 95% CI: -35.1 to -2.8). Metabolism increased with LR, with LR mice having a greater M3G-to-morphine ratio compared with DIO (MD: 5.3; 95% CI: 0.3-10.4). Systemic effects associated with obesity decrease morphine metabolism and excretion. A previous study from our laboratory demonstrated that obesity and leptin deficiency decrease the sensitivity of central respiratory control centers to carbon dioxide. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance, and replacing leptin attenuated the PK changes associated with leptin deficiency, suggesting leptin has a direct role in morphine metabolism.

Intraoperative and postoperative feasibility and safety of total tubeless, tubeless, small-bore tube, and standard percutaneous nephrolithotomy: a systematic review and network meta-analysis of 16 randomized controlled trials.

PubMed

Lee, Joo Yong; Jeh, Seong Uk; Kim, Man Deuk; Kang, Dong Hyuk; Kwon, Jong Kyou; Ham, Won Sik; Choi, Young Deuk; Cho, Kang Su

2017-06-27

Percutaneous nephrolithotomy (PCNL) is performed to treat relatively large renal stones. Recent publications indicate that tubeless and total tubeless (stentless) PCNL is safe in selected patients. We performed a systematic review and network meta-analysis to evaluate the feasibility and safety of different PCNL procedures, including total tubeless, tubeless with stent, small-bore tube, and large-bore tube PCNLs. PubMed, Cochrane Central Register of Controlled Trials, and EMBASE™ databases were searched to identify randomized controlled trials published before December 30, 2013. One researcher examined all titles and abstracts found by the searches. Two investigators independently evaluated the full-text articles to determine whether those met the inclusion criteria. Qualities of included studies were rated with Cochrane's risk-of-bias assessment tool. Sixteen studies were included in the final syntheses including pairwise and network meta-analyses. Operation time, pain scores, and transfusion rates were not significantly different between PCNL procedures. Network meta-analyses demonstrated that for hemoglobin changes, total tubeless PCNL may be superior to standard PCNL (mean difference [MD] 0.65, 95% CI 0.14-1.13) and tubeless PCNLs with stent (MD -1.14, 95% CI -1.65--0.62), and small-bore PCNL may be superior to tubeless PCNL with stent (MD 1.30, 95% CI 0.27-2.26). Network meta-analyses also showed that for length of hospital stay, total tubeless (MD 1.33, 95% CI 0.23-2.43) and tubeless PCNLs with stent (MD 0.99, 95% CI 0.19-1.79) may be superior to standard PCNL. In rank probability tests, small-bore tube and total tubeless PCNLs were superior for operation time, pain scores, and hemoglobin changes. For hemoglobin changes, total tubeless and small-bore PCNLs may be superior to other methods. For hospital stay, total tubeless and tubeless PCNLs with stent may be superior to other procedures.

77 FR 56874 - Extension of Comment Period: Remedies for Small Copyright Claims: Additional Comments

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77 FR 38043 - Great Lakes Hydro America, LLC; Notice of Application Accepted for Filing and Soliciting Comments...

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2012-06-26

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Federal Register 2010, 2011, 2012, 2013, 2014

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Growth hormone for intestinal adaptation in patients with short bowel syndrome: systematic review and meta-analysis of randomized controlled trials.

PubMed

Guo, Ming-Xiao; Li, You-Sheng; Fan, Lei; Li, Jie-Shou

2011-06-01

The purpose of this systematic review was to assess the efficacy of growth hormone (GH) treatment in patients with short bowel syndrome (SBS). Electronic searches were performed to identify all publications describing randomized controlled trials (RCTs) on the use of GH with or without glutamine for the treatment of patients with SBS. The outcomes of interest were body weight, lean body mass, and intestinal absorption function. Four trials involving 70 patients were included in the review. A meta-analysis of these trials suggested that GH had a positive effect in terms of increased weight (mean difference [MD] = 1.66; 95% CI, 0.69-2.63, P < 0.001), lean body mass (MD = 1.93; 95% CI, 0.97-2.90; P < 0.001), energy absorption (MD = 4.42; 95% CI, 0.26-8.58; P = 0.04), nitrogen absorption (MD = 4.85; 95% CI, 0.20-9.49; P = 0.04), and fat absorption (MD = 5.02; 95% CI, 0.21-9.82; P = 0.04) for patients with SBS. Adverse effects occurred during active treatment in all trials. Only 1 trial included a 12-week follow-up study. The results suggest a possible short-term benefit in terms of body weight, lean body mass, and absorptive capacities; however, no conclusion of long-term efficacy of GH could be obtained. Large-scale, long-term follow-up RCTs are needed to confirm the efficacy and tolerability of GH in the future.

Rating scales for musician's dystonia

PubMed Central

Berque, Patrice; Jabusch, Hans-Christian; Altenmüller, Eckart; Frucht, Steven J.

2013-01-01

Musician's dystonia (MD) is a focal adult-onset dystonia most commonly involving the hand. It has much greater relative prevalence than non-musician’s focal hand dystonias, exhibits task specificity at the level of specific musical passages, and is a particularly difficult form of dystonia to treat. For most MD patients, the diagnosis confirms the end of their music performance careers. Research on treatments and pathophysiology is contingent upon measures of motor function abnormalities. In this review, we comprehensively survey the literature to identify the rating scales used in MD and the distribution of their use. We also summarize the extent to which the scales have been evaluated for their clinical utility, including reliability, validity, sensitivity, specificity to MD, and practicality for a clinical setting. Out of 135 publications, almost half (62) included no quantitative measures of motor function. The remaining 73 studies used a variety of choices from among 10 major rating scales. Most used subjective scales involving either patient or clinician ratings. Only 25% (18) of the studies used objective scales. None of the scales has been completely and rigorously evaluated for clinical utility. Whether studies involved treatments or pathophysiologic assays, there was a heterogeneous choice of rating scales used with no clear standard. As a result, the collective interpretive value of those studies is limited because the results are confounded by measurement effects. We suggest that the development and widespread adoption of a new clinically useful rating scale is critical for accelerating basic and clinical research in MD. PMID:23884039

Pathways to rural family practice at Memorial University of Newfoundland

PubMed Central

Rourke, James; O’Keefe, Danielle; Ravalia, Mohamed; Moffatt, Scott; Parsons, Wanda; Duggan, Norah; Stringer, Katherine; Jong, Michael; Walsh, Kristin Harris; Hippe, Janelle

2018-01-01

Abstract Objective To assess Memorial University of Newfoundland’s (MUN’s) commitment to a comprehensive pathways approach to rural family practice, and to determine the national and provincial effects of applying this approach. Design Analysis of anonymized secondary data. Setting Canada. Participants Memorial’s medical degree (MD) graduates practising family medicine in Newfoundland and Labrador as of January 2015 (N = 305), MUN’s 2011 and 2012 MD graduates (N = 120), and physicians who completed family medicine training programs in Canada between 2004 and 2013 and who were practising in Canada 2 years after completion of their postgraduate training (N = 8091). Main outcome measures National effect was measured by the proportion of MUN’s family medicine program graduates practising in rural Canada compared with those from other Canadian family medicine training programs. Provincial effect was measured by the location of MUN’s MD graduates practising family medicine in Newfoundland and Labrador as of January 2015. Commitment to a comprehensive pathways approach to rural family practice was measured by anonymized geographic data on admissions, educational placements, and practice locations of MUN’s 2011 and 2012 MD graduates, including those who completed family medicine residencies at MUN. Results Memorial’s comprehensive pathways approach to training physicians for rural practice was successful on both national and provincial levels: 26.9% of MUN family medicine program graduates were in a rural practice location 2 years after exiting their post-MD training from 2004 to 2013 compared with the national rate of 13.3% (national effect); 305 of MUN’s MD graduates were practising family medicine in Newfoundland and Labrador as of 2015, with 36% practising in rural areas (provincial effect). Of 114 MD students with known background who graduated in 2011 and 2012, 32% had rural backgrounds. Memorial’s 2011 and 2012 MD graduates spent 20% of all clinical placement weeks in rural areas; of note, 90% of all first-year placements and 95% of third-year family medicine clerkship placements were rural. For the 25 MUN 2011 and 2012 MD graduates who also completed family medicine residencies at MUN, 38% of family medicine placement weeks were spent in rural communities or rural towns. Of the 30 MUN 2011 and 2012 MD graduates practising family medicine in Canada as of January 2015, 42% were practising in rural communities or rural towns; 73% were practising in Newfoundland and Labrador and half of those were in rural communities and rural towns. Conclusion A comprehensive rural pathways approach that includes recruiting rural students and exposing all medical students to extensive rural placements and all family medicine residents to rural family practice training has resulted in more rural generalist physicians in family practice in Newfoundland and Labrador and across Canada. PMID:29540400

Pathways to rural family practice at Memorial University of Newfoundland.

PubMed

Rourke, James; O'Keefe, Danielle; Ravalia, Mohamed; Moffatt, Scott; Parsons, Wanda; Duggan, Norah; Stringer, Katherine; Jong, Michael; Walsh, Kristin Harris; Hippe, Janelle

2018-03-01

To assess Memorial University of Newfoundland's (MUN's) commitment to a comprehensive pathways approach to rural family practice, and to determine the national and provincial effects of applying this approach. Analysis of anonymized secondary data. Canada. Memorial's medical degree (MD) graduates practising family medicine in Newfoundland and Labrador as of January 2015 (N = 305), MUN's 2011 and 2012 MD graduates (N = 120), and physicians who completed family medicine training programs in Canada between 2004 and 2013 and who were practising in Canada 2 years after completion of their postgraduate training (N = 8091). National effect was measured by the proportion of MUN's family medicine program graduates practising in rural Canada compared with those from other Canadian family medicine training programs. Provincial effect was measured by the location of MUN's MD graduates practising family medicine in Newfoundland and Labrador as of January 2015. Commitment to a comprehensive pathways approach to rural family practice was measured by anonymized geographic data on admissions, educational placements, and practice locations of MUN's 2011 and 2012 MD graduates, including those who completed family medicine residencies at MUN. Memorial's comprehensive pathways approach to training physicians for rural practice was successful on both national and provincial levels: 26.9% of MUN family medicine program graduates were in a rural practice location 2 years after exiting their post-MD training from 2004 to 2013 compared with the national rate of 13.3% (national effect); 305 of MUN's MD graduates were practising family medicine in Newfoundland and Labrador as of 2015, with 36% practising in rural areas (provincial effect). Of 114 MD students with known background who graduated in 2011 and 2012, 32% had rural backgrounds. Memorial's 2011 and 2012 MD graduates spent 20% of all clinical placement weeks in rural areas; of note, 90% of all first-year placements and 95% of third-year family medicine clerkship placements were rural. For the 25 MUN 2011 and 2012 MD graduates who also completed family medicine residencies at MUN, 38% of family medicine placement weeks were spent in rural communities or rural towns. Of the 30 MUN 2011 and 2012 MD graduates practising family medicine in Canada as of January 2015, 42% were practising in rural communities or rural towns; 73% were practising in Newfoundland and Labrador and half of those were in rural communities and rural towns. A comprehensive rural pathways approach that includes recruiting rural students and exposing all medical students to extensive rural placements and all family medicine residents to rural family practice training has resulted in more rural generalist physicians in family practice in Newfoundland and Labrador and across Canada. Copyright© the College of Family Physicians of Canada.

The brain and the biology of belief: An interview with Andrew Newberg, MD. Interview by Nancy Nachman-Hunt.

PubMed

Newberg, Andrew

2009-01-01

Andrew Newberg, MD, is an associate professor in the Department of Radiology, Division of Nuclear Medicine, at the Hospital of the University of Pennsylvania, Philadelphia, with secondary appointments in the Departments of Psychiatry and Religious Studies. He is actively involved in neuroimaging research projects, including the study of the neurophysiological correlates of meditation and other types of complementary therapies. Dr Newberg's research now largely focuses on how brain function is associated with various mental states, in particular, the relationship between brain function and mystical or religious experiences. He has authored several books, including Why God Won't Go Away: Brain Science and the Biology of Belief (Ballantine/Random House, 2001) and coauthor with Eugene G. d'Aquili, MD, of The Mystical Mind: Probing the Biology of Religious Experience (Fortress Press, 1999). His most recent book is How God Changes Your Brain, with coauthor Mark Waldman (Ballantine Books, 2009).

Oropharyngeal dysphagia in myotonic dystrophy type 1: a systematic review.

PubMed

Pilz, Walmari; Baijens, Laura W J; Kremer, Bernd

2014-06-01

A systematic review was conducted to investigate the pathophysiology of and diagnostic procedures for oropharyngeal dysphagia in myotonic dystrophy (MD). The electronic databases Embase, PubMed, and The Cochrane Library were used. The search was limited to English, Dutch, French, German, Spanish, and Portuguese publications. Sixteen studies met the inclusion criteria. Two independent reviewers assessed the methodological quality of the included articles. Swallowing assessment tools, the corresponding protocols, the studies' outcome measurements, and main findings are summarized and presented. The body of literature on pathophysiology of swallowing in dysphagic patients with MD type 1 remains scant. The included studies are heterogeneous with respect to design and outcome measures and hence are not directly comparable. More importantly, most studies had methodological problems. These are discussed in detail and recommendations for further research on diagnostic examinations for swallowing disorders in patients with MD type 1 are provided.

75 FR 6162 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-81 (MD-81), DC-9-82 (MD-82...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... Corporation Model DC- 9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes... Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 airplanes. This...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service...

75 FR 76482 - Notice of Web Availability and Opportunity for Public Comment on Updated Guidance for the Section...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-08

... activities after selection of Section 202 and Section 811 applications for fund reservations, including mixed.... There are two methods of submitting public comments: 1. Submission of Comments by Mail. Comments may be...

Muscle Dysmorphia Symptomatology and Associated Psychological Features in Bodybuilders and Non-Bodybuilder Resistance Trainers: A Systematic Review and Meta-Analysis.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Cobley, Stephen; Hackett, Daniel; Gifford, Janelle; Capling, Louise; O'Connor, Helen

2017-02-01

Muscle dysmorphia (MD) is associated with a self-perceived lack of size and muscularity, and is characterized by a preoccupation with and pursuit of a hyper-mesomorphic body. MD symptoms may hypothetically be more prevalent in bodybuilders (BBs) than in non-bodybuilder resistance trainers (NBBRTs). Our objective was to compare MD symptomatology in BBs versus NBBRTs and identify psychological and other characteristics associated with MD in these groups. We searched relevant databases from earliest record to February 2015 for studies examining MD symptoms in BBs and/or NBBRTs. Included studies needed to assess MD using a psychometrically validated assessment tool. Study quality was evaluated using an adapted version of the validated Downs and Black tool. We calculated between-group standardized mean difference (effect sizes [ESs]) and 95 % confidence intervals (CIs) for each MD subscale, and performed meta-analysis when five or more studies used the same MD tool. We also extracted data describing psychological or other characteristics associated with MD. Of the 2135 studies initially identified, 31 analyzing data on 5880 participants (BBs: n = 1895, NBBRTs: n = 3523, controls: n = 462) were eligible for inclusion, though study quality was generally poor-moderate (range 7-19/22). Most participants were male (90 %). Eight different MD assessment tools were used. Meta-analysis for five studies all using the Muscle Dysmorphia Inventory (MDI) revealed there was a medium to large pooled ES for greater MD symptomatology in BBs than in NBBRTs on all MDI subscales (ES 0.53-1.12; p ≤ 0.01). Competitive BBs scored higher than non-competitive BBs (ES 1.21, 95 % CI 0.82-1.60; p < 0.001). MD symptoms were associated with anxiety (r 0.32-0.42; p ≤ 0.01), social physique anxiety (r 0.26-0.75; p < 0.01), depression (r 0.23-0.53; p ≤ 0.01), neuroticism (r 0.38; p < 0.001), and perfectionism (r 0.35; p < 0.05) and were inversely associated with self-concept (r -0.32 to -0.36; p < 0.01) and self-esteem (r -0.42 to -0.47; p < 0.01). MD symptomatology was greater in BBs than in NBBRTs. Anxiety and social physique anxiety, depression, neuroticism, and perfectionism were positively associated with MD, while self-concept and self-esteem were negatively associated. It remains unclear whether these characteristics are exacerbated by bodybuilding, or whether individuals with these characteristics are attracted to the bodybuilding context.

A-MUPS score to differentiate patients with somatic symptom disorder from those with medical disease for complaints of non-acute pain

PubMed Central

Suzuki, Shingo; Ohira, Yoshiyuki; Noda, Kazutaka; Ikusaka, Masatomi

2017-01-01

Purpose To develop a clinical score to discriminate patients with somatic symptom disorder (SSD) from those with medical disease (MD) for complaints of non-acute pain. Methods We retrospectively examined the clinical records of consecutive patients with pain for a duration of ≥1 month in our department from April 2003 to March 2015. We divided the subjects according to the diagnoses of definite SSD (as diagnosed and tracked by psychiatrists in our hospital), probable SSD (without evaluation by psychiatrists in our hospital), matched MD (randomly matched two patients by age, sex, and pain location for each definite SSD patient), unmatched MD, other mental disease, or functional somatic syndrome (FSS). We investigated eight clinical factors for definite SSD and matched MD, and developed a diagnostic score to identify SSD. We subsequently validated the model with cases of probable SSD and unmatched MD. Results The number of patients with definite SSD, probable SSD, matched MD, unmatched MD, other mental disease, and FSS was 104 (3.5%), 214 (7.3%), 197 (6.7%), 742 (25%), 708 (24%), and 978 (33%), respectively. In a conditional logistic regression analysis, the following five factors were included as independent predictors of SSD: Analgesics ineffective, Mental disorder history, Unclear provocative/palliative factors, Persistence without cessation, and Stress feelings/episodes (A-MUPS). The area under the receiver operating characteristic curve (AUC) of the model was 0.900 (95% CI: 0.864–0.937, p<0.001), and the McFadden’s pseudo-R-squared was 0.709. For internal validation, the AUC between probable SSD and unmatched MD was 0.930 (95% CI: 0.910–0.950, p<0.001). The prevalence and the likelihood ratio of SSD increased as the score increased. Conclusion The A-MUPS score was useful for discriminating patients with SSD from those with MD for complaints of non-acute pain, although external validation and refinement should be needed. PMID:28652807

A-MUPS score to differentiate patients with somatic symptom disorder from those with medical disease for complaints of non-acute pain.

PubMed

Suzuki, Shingo; Ohira, Yoshiyuki; Noda, Kazutaka; Ikusaka, Masatomi

2017-01-01

To develop a clinical score to discriminate patients with somatic symptom disorder (SSD) from those with medical disease (MD) for complaints of non-acute pain. We retrospectively examined the clinical records of consecutive patients with pain for a duration of ≥1 month in our department from April 2003 to March 2015. We divided the subjects according to the diagnoses of definite SSD (as diagnosed and tracked by psychiatrists in our hospital), probable SSD (without evaluation by psychiatrists in our hospital), matched MD (randomly matched two patients by age, sex, and pain location for each definite SSD patient), unmatched MD, other mental disease, or functional somatic syndrome (FSS). We investigated eight clinical factors for definite SSD and matched MD, and developed a diagnostic score to identify SSD. We subsequently validated the model with cases of probable SSD and unmatched MD. The number of patients with definite SSD, probable SSD, matched MD, unmatched MD, other mental disease, and FSS was 104 (3.5%), 214 (7.3%), 197 (6.7%), 742 (25%), 708 (24%), and 978 (33%), respectively. In a conditional logistic regression analysis, the following five factors were included as independent predictors of SSD: Analgesics ineffective, Mental disorder history, Unclear provocative/palliative factors, Persistence without cessation, and Stress feelings/episodes (A-MUPS). The area under the receiver operating characteristic curve (AUC) of the model was 0.900 (95% CI: 0.864-0.937, p <0.001), and the McFadden's pseudo- R -squared was 0.709. For internal validation, the AUC between probable SSD and unmatched MD was 0.930 (95% CI: 0.910-0.950, p <0.001). The prevalence and the likelihood ratio of SSD increased as the score increased. The A-MUPS score was useful for discriminating patients with SSD from those with MD for complaints of non-acute pain, although external validation and refinement should be needed.

Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy

PubMed Central

Wu, Yuan; Yao, Xun; Vespasiani, Giacomo; Nicolucci, Antonio; Dong, Yajie; Kwong, Joey; Li, Ling; Sun, Xin

2017-01-01

Background Mobile health apps for diabetes self-management have different functions. However, the efficacy and safety of each function are not well studied, and no classification is available for these functions. Objective The aims of this study were to (1) develop and validate a taxonomy of apps for diabetes self-management, (2) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of randomized controlled trials (RCTs), and (3) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy. Methods We developed a 3-axis taxonomy with columns of clinical modules, rows of functional modules and cells of functions with risk assessments. This taxonomy was validated by reviewing and classifying commercially available diabetes apps. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database, and ClinicalTrials.gov from January 2007 to May 2016. We included RCTs of adult outpatients with diabetes that compared using mobile app-based interventions with usual care alone. The mean differences (MDs) in hemoglobin A1c (HbA1c) concentrations and risk ratios of adverse events were pooled using a random-effects meta-analysis. After taxonomic classification, we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions. Results Across 12 included trials involving 974 participants, using app-based interventions was associated with a clinically significant reduction of HbA1c (MD 0.48%, 95% CI 0.19%-0.78%) without excess adverse events. Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes (MD 0.67%, 95% CI 0.30%-1.03% vs MD 0.37%, 95% CI –0.12%-0.86%). Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction (with complication prevention: MD 1.31%, 95% CI 0.66%-1.96% vs without: MD 0.38%, 95% CI 0.09%-0.67%; intersubgroup P=.01), as was having a structured display (with structured display: MD 0.69%, 95% CI 0.32%-1.06% vs without: MD 0.69%, 95% CI –0.18%-0.53%; intersubgroup P=.03). However, having a clinical decision-making function was not associated with a larger HbA1c reduction (with clinical decision making: MD 0.19%, 95% CI –0.24%-0.63% vs without: MD 0.61%, 95% CI 0.27%-0.95%; intersubgroup P=.14). Conclusions The use of mobile app-based interventions yields a clinically significant HbA1c reduction among adult outpatients with diabetes, especially among those with type 2 diabetes. Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps. PMID:28292740

Substructured multibody molecular dynamics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James

2006-11-01

We have enhanced our parallel molecular dynamics (MD) simulation software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator, lammps.sandia.gov) to include many new features for accelerated simulation including articulated rigid body dynamics via coupling to the Rensselaer Polytechnic Institute code POEMS (Parallelizable Open-source Efficient Multibody Software). We use new features of the LAMMPS software package to investigate rhodopsin photoisomerization, and water model surface tension and capillary waves at the vapor-liquid interface. Finally, we motivate the recipes of MD for practitioners and researchers in numerical analysis and computational mechanics.

78 FR 20164 - Self-Regulatory Organizations; NYSE Arca, Inc.; Response to Comments Submitted After the Issuance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

... data, views, and arguments concerning the Approval Order, including whether Amendment No. 1 to the... commenter discussed the existing unloading queues for metals, including copper, at LME warehouses.\\18\\ The commenter asserted that queues to unload copper from LME warehouses appear to be lengthening because owners...

Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1

PubMed Central

Feng, Xinxin; An, Yuyan; Zheng, Jie; Sun, Miao; Wang, Liangju

2016-01-01

Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-free separation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related genes. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX, and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin-related verification in apple calli suggested that the regulation of MdMADS1 on anthocyanin biosynthesis was partially independent of fruit ripening process. Taken together, our findings provide insight into the mechanism how ALA regulates anthocyanin accumulation and add new information on transcriptase regulators of fruit coloration. PMID:27872628

Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and Combined Pharmacotherapy.

PubMed

Loreto, Aline Rodrigues; Carvalho, Carlos Felipe Cavalcanti; Frallonardo, Fernanda Piotto; Ismael, Flavia; Andrade, Arthur Guerra de; Castaldelli-Maia, João Maurício

2017-01-01

The aim of this study was to investigate smoking treatment effectiveness and retention in a population with and without mental disorders (MD). Participants received cognitive behavioral therapy (CBT) plus nicotine patch alone or in combination with other medications (i.e., gum, bupropion, or nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care Center unit (CAPS), taking into account sociodemographics and smoking profile covariates. The study involved comparison of treatment success (seven-day point prevalence abstinence at the end of the treatment) and retention (presence of the individual in all of the four medical consultations and six group sessions) in two subsamples of patients with MD (n = 267) and without MD (n = 397) who were included in a six-week treatment provided by a CAPS from 2007 to 2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine patches, nicotine gums, and bupropion and nortriptyline available, prescribed by psychiatrists). Within patients with MD, CBT plus nicotine patch plus bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI [0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80, 95% CI [0.65, 0.99], p = .048) were associated with treatment success. No variable was associated with dropout or retention within patients with or without MD. Our findings support the use of CBT plus nicotine patch plus bupropion as well as CBT plus nicotine patch plus gum in samples with high rates of medical, psychiatric, and addiction disorders. These findings support those of previous studies in the general population. Pharmacological treatment associated with group CBT based on cognitive-behavioral concepts and combined with ongoing MD treatment seems to be the best option for smoking cessation treatment among patients with MD. Units that deal with patients with MD, such as CAPS in Brazil, should be encouraged to treat smoking addiction in this population. Future studies should investigate retention rates in other samples of patients with MD.

From Skeptic to Vital Partner in Massage Therapy Research: an Interview with Mark Hyman Rapaport, MD.

PubMed

Kennedy, Ann Blair

2018-06-01

Mark Hyman Rapaport, MD is a highly accomplished researcher, academician, and clinician. Dr. Rapaport has more than 180 publications, and his main research interests include biologic genesis of anxiety disorders, as well as immunity abnormalities and depression in mood disorders. His research investigating massage therapy has included study of inflammatory biomarkers, cancer related fatigue, and generalized anxiety disorder. He has created a successful partnership with the Atlanta School of Massage for the implementation of his research inquiry. Dr. Rapaport discusses with us a wide range of topics on massage therapy, including from where his inspiration for research comes.

78 FR 72001 - Amendment of Class D and E Airspace, and Establishment of Class E Airspace; Salisbury, MD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-02

...'' W.) That airspace extending upward from the surface to and including 2,500 feet MSL [[Page 72002...] Salisbury-Ocean City Wicomico Regional Airport, MD (Lat. 38[deg]20'25'' N., long. 75[deg]30'34'' W.) That... (Lat. 38[deg]20'25'' N., long. 75[deg]30'34'' W.) That airspace extending upward from the surface...

Conceptual Regional Sediment Budget for USACE North Atlantic Division

DTIC Science & Technology

2015-03-01

sediment budget is the first phase in development of the working budget and is intended to provide a general framework based on existing transport ...existing literature and databases were reviewed and analyzed to characterize sediment transport pathways and magnitudes, and morphologic zones of...net sediment transport pathways for Region 1 (includes NACCS planning regions VA1 through VA6 and MD2 through MD5

A tribute to francis fontan, MD, and guillermo kreutzer, MD.

PubMed

Mavroudis, Constantine

2012-04-01

At the Third Scientific Meeting of the World Society for Pediatric and Congenital Heart Surgery in June 2011 in Istanbul, Turkey, Professor Francis Fontan and Dr Guillermo Kreutzer were honored for their contributions to the world of pediatric and congenital heart surgery. The presentation included a video of each physician being interviewed about their clinical and historical experiences. The presentation and videos are summarized herein.

Developing the MD Explorer

NASA Astrophysics Data System (ADS)

Howie, Philip V.

1993-04-01

The MD Explorer is an eight-seat twin-turbine engine helicopter which is being developed using integrated product definition (IPD) team methodology. New techniques include NOTAR antitorque system for directional control, a composite fuselage, an all-composite bearingless main rotor, and digital cockpit displays. Three-dimensional CAD models are the basis of the entire Explorer design. Solid models provide vendor with design clarification, removing much of the normal drawing interpretation errors.

Probiotics, prebiotics infant formula use in preterm or low birth weight infants: a systematic review

PubMed Central

2012-01-01

Background Previous reviews (2005 to 2009) on preterm infants given probiotics or prebiotics with breast milk or mixed feeds focused on prevention of Necrotizing Enterocolitis, sepsis and diarrhea. This review assessed if probiotics, prebiotics led to improved growth and clinical outcomes in formula fed preterm infants. Methods Cochrane methodology was followed using randomized controlled trials (RCTs) which compared preterm formula containing probiotic(s) or prebiotic(s) to conventional preterm formula in preterm infants. The mean difference (MD) and corresponding 95% confidence intervals (CI) were reported for continuous outcomes, risk ratio (RR) and corresponding 95% CI for dichotomous outcomes. Heterogeneity was assessed by visual inspection of forest plots and a chi2 test. An I2 test assessed inconsistencies across studies. I2> 50% represented substantial heterogeneity. Results Four probiotics studies (N=212), 4 prebiotics studies (N=126) were included. Probiotics: There were no significant differences in weight gain (MD 1.96, 95% CI: -2.64 to 6.56, 2 studies, n=34) or in maximal enteral feed (MD 35.20, 95% CI: -7.61 to 78.02, 2 studies, n=34), number of stools per day increased significantly in probiotic group (MD 1.60, 95% CI: 1.20 to 2.00, 1 study, n=20). Prebiotics: Galacto-oligosaccharide / Fructo-oligosaccharide (GOS/FOS) yielded no significant difference in weight gain (MD 0.04, 95% CI: -2.65 to 2.73, 2 studies, n=50), GOS/FOS yielded no significant differences in length gain (MD 0.01, 95% CI: -0.03 to 0.04, 2 studies, n=50). There were no significant differences in head growth (MD −0.01, 95% CI: -0.02 to 0.00, 2 studies, n=76) or age at full enteral feed (MD −0.79, 95% CI: -2.20 to 0.61, 2 studies, n=86). Stool frequency increased significantly in prebiotic group (MD 0.80, 95% CI: 0.48 to 1.1, 2 studies, n=86). GOS/FOS and FOS yielded higher bifidobacteria counts in prebiotics group (MD 2.10, 95% CI: 0.96 to 3.24, n=27) and (MD 0.48, 95% CI: 0.28 to 0.68, n=56). Conclusions There is not enough evidence to state that supplementation with probiotics or prebiotics results in improved growth and clinical outcomes in exclusively formula fed preterm infants. PMID:22928998

Summary of EPA’s Review of Comments on the National Electric Energy Data System (NEEDS) v.5.15

EPA Pesticide Factsheets

This document summarizes EPA’s review of comments on inputs to the IPM, including the National Electric Energy Data System (NEEDS) database. and highlights common comment types and how EPA generally reviewed and acted on those comments.

77 FR 4542 - Proposed Information Collection; Comment Request; Special Census Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

... information technology. Comments submitted in response to this notice will be summarized and/or included in... DEPARTMENT OF COMMERCE U.S. Census Bureau Proposed Information Collection; Comment Request... other Federal agencies to take this opportunity to comment on proposed and/or continuing information...

Md-miR156ab and Md-miR395 Target WRKY Transcription Factors to Influence Apple Resistance to Leaf Spot Disease.

PubMed

Zhang, Qiulei; Li, Yang; Zhang, Yi; Wu, Chuanbao; Wang, Shengnan; Hao, Li; Wang, Shengyuan; Li, Tianzhong

2017-01-01

MicroRNAs (miRNAs) are key regulators of gene expression that post-transcriptionally regulate transcription factors involved in plant physiological activities. Little is known about the effects of miRNAs in disease resistance in apple ( Malus × domestica ). We globally profiled miRNAs in the apple cultivar Golden Delicious (GD) infected or not with the apple leaf spot fungus Alternaria alternaria f. sp. mali (ALT1), and identified 58 miRNAs that exhibited more than a 2-fold upregulation upon ALT1 infection. We identified a pair of miRNAs that target protein-coding genes involved in the defense response against fungal pathogens; Md-miR156ab targets a novel WRKY transcription factor, MdWRKYN1, which harbors a TIR and a WRKY domain. Md-miR395 targets another transcription factor, MdWRKY26, which contains two WRKY domains. Real-time PCR analysis showed that Md-miR156ab and Md-miR395 levels increased, while MdWRKYN1 and MdWRKY26 expression decreased in ALT1-inoculated GD leaves; furthermore, the overexpression of Md-miR156ab and Md-miR395 resulted in a significant reduction in MdWRKYN1 and MdWRKY26 expression. To investigate whether these miRNAs and their targets play a crucial role in plant defense, we overexpressed MdWRKYN1 or knocked down Md-miR156ab activity, which in both cases enhanced the disease resistance of the plants by upregulating the expression of the WRKY-regulated pathogenesis-related (PR) protein-encoding genes MdPR3-1, MdPR3-2, MdPR4, MdPR5, MdPR10-1 , and MdPR10-2 . In a similar analysis, we overexpressed MdWRKY26 or suppressed Md-miR395 activity, and found that many PR protein-encoding genes were also regulated by MdWRKY26 . In GD, ALT-induced Md-miR156ab and Md-miR395 suppress MdWRKYN1 and MdWRKY26 expression, thereby decreasing the expression of some PR genes, and resulting in susceptibility to ALT1.

Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving Ethylene-Responsive Factor.

PubMed

Li, Tong; Tan, Dongmei; Liu, Zhi; Jiang, Zhongyu; Wei, Yun; Zhang, Lichao; Li, Xinyue; Yuan, Hui; Wang, Aide

2015-10-01

Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during fruit development is unclear. Here, we characterized another apple (Malus×domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not only in fruits but also in other tissues. During fruit development, MdACS6 was initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be expressed at 35 d before harvest and immediateley after harvest, respectively. Moreover, the enzyme activity of MdACS6 was significantly lower than that of MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits. Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in control fruits. In MdACS6 apple fruits silenced by the virus-induced gene silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a transcript was detectable. In order to explore the mechanism through which MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple ethylene-responsive factor (ERF) genes. The results showed that the expression of MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast one-hybrid assay showed that MdERF2 protein could bind to the promoter of MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was discussed. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Relationship between visual field progression and baseline refraction in primary open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Umeda, Yuzo; Shiraga, Fumio

2016-01-01

To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma. In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction. A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran-Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03-1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94-0.99) had a significant association with MD slope deterioration. In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.

The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane.

PubMed

Tanimura, Natsuko; Saitoh, Shin-Ichiroh; Ohto, Umeharu; Akashi-Takamura, Sachiko; Fujimoto, Yukari; Fukase, Koichi; Shimizu, Toshiyuki; Miyake, Kensuke

2014-06-01

TLR4/MD-2 senses lipid A, activating the MyD88-signaling pathway on the plasma membrane and the TRIF-signaling pathway after CD14-mediated TLR4/MD-2 internalization into endosomes. Monophosphoryl lipid A (MPL), a detoxified derivative of lipid A, is weaker than lipid A in activating the MyD88-dependent pathway. Little is known, however, about mechanisms underlying the attenuated activation of MyD88-dependent pathways. We here show that MPL was impaired in induction of CD14-dependent TLR4/MD-2 dimerization compared with lipid A. Impaired TLR4/MD-2 dimerization decreased CD14-mediated TNFα production. In contrast, MPL was comparable to lipid A in CD14-independent MyD88-dependent TNFα production and TRIF-dependent responses including cell surface CD86 up-regulation and IFNβ induction. Although CD86 up-regulation is dependent on TRIF signaling, it was induced by TLR4/MD-2 at the plasma membrane. These results revealed that the attenuated MPL responses were due to CD14-initiated responses at the plasma membrane, but not just to responses initiated by MyD88, that is, MPL was specifically unable to induce CD14-dependent TLR4/MD-2 dimerization that selectively enhances MyD88-mediated responses at the plasma membrane. © The Japanese Society for Immunology. 2013. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Phylogenetic analysis of IDD gene family and characterization of its expression in response to flower induction in Malus.

PubMed

Fan, Sheng; Zhang, Dong; Xing, Libo; Qi, Siyan; Du, Lisha; Wu, Haiqin; Shao, Hongxia; Li, Youmei; Ma, Juanjuan; Han, Mingyu

2017-08-01

Although INDETERMINATE DOMAIN (IDD) genes encoding specific plant transcription factors have important roles in plant growth and development, little is known about apple IDD (MdIDD) genes and their potential functions in the flower induction. In this study, we identified 20 putative IDD genes in apple and named them according to their chromosomal locations. All identified MdIDD genes shared a conserved IDD domain. A phylogenetic analysis separated MdIDDs and other plant IDD genes into four groups. Bioinformatic analysis of chemical characteristics, gene structure, and prediction of protein-protein interactions demonstrated the functional and structural diversity of MdIDD genes. To further uncover their potential functions, we performed analysis of tandem, synteny, and gene duplications, which indicated several paired homologs of IDD genes between apple and Arabidopsis. Additionally, genome duplications also promoted the expansion and evolution of the MdIDD genes. Quantitative real-time PCR revealed that all the MdIDD genes showed distinct expression levels in five different tissues (stems, leaves, buds, flowers, and fruits). Furthermore, the expression levels of candidate MdIDD genes were also investigated in response to various circumstances, including GA treatment (decreased the flowering rate), sugar treatment (increased the flowering rate), alternate-bearing conditions, and two varieties with different-flowering intensities. Parts of them were affected by exogenous treatments and showed different expression patterns. Additionally, changes in response to alternate-bearing and different-flowering varieties of apple trees indicated that they were also responsive to flower induction. Taken together, our comprehensive analysis provided valuable information for further analysis of IDD genes aiming at flower induction.

Targeting myeloid differentiation protein 2 by the new chalcone L2H21 protects LPS-induced acute lung injury.

PubMed

Zhang, Yali; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Pan, Zheer; Huang, Yi; Mei, Liqin; Dai, Yuanrong; Liu, Xing; Shan, Xiaoou; Liang, Guang

2017-04-01

Acute inflammatory diseases are the leading causes of mortality in intensive care units. Myeloid differentiation 2 (MD-2) is required for recognizing lipopolysaccharide (LPS) by toll-like receptor 4 (TLR4), and represents an attractive therapeutic target for LPS-induced inflammatory diseases. In this study, we report a chalcone derivative, L2H21, as a new MD2 inhibitor, which could inhibit LPS-induced inflammation both in vitro and in vivo. We identify that L2H21 as a direct inhibitor of MD-2 by binding to Arg 90 and Tyr 102 residues in MD-2 hydrophobic pocket using a series of biochemical experiments, including surface plasmon response, molecular docking and amino acid mutation. L2H21 dose dependently inhibited LPS-induced inflammatory cytokine expression in primary macrophages. In mice with LPS intratracheal instillation, L2H21 significantly decreased LPS-induced pulmonary oedema, pathological changes in lung tissue, protein concentration increase in bronchoalveolar lavage fluid, inflammatory cells infiltration and inflammatory gene expression, accompanied with the decrease in pulmonary TLR4/MD-2 complex. Meanwhile, administration with L2H21 protects mice from LPS-induced mortality at a degree of 100%. Taken together, this study identifies a new MD2 inhibitor L2H21 as a promising candidate for the treatment of acute lung injury (ALI) and sepsis, and validates that inhibition of MD-2 is a potential therapeutic strategy for ALI. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity‐related temperaments in young healthy adults

PubMed Central

Taki, Yasuyuki; Sekiguchi, Atsushi; Hashizume, Hiroshi; Nouchi, Rui; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

2015-01-01

Abstract Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right‐handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self‐directedness, and higher self‐transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking. Hum Brain Mapp 36:1808–1827, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:25627674

Reliability and validity of the anesthesiologist supervision instrument when certified registered nurse anesthetists provide scores.

PubMed

Dexter, Franklin; Masursky, Danielle; Hindman, Bradley J

2015-01-01

At many facilities in the United States, supervision of Certified Registered Nurse Anesthetists (CRNAs) is a major daily responsibility of anesthesiologists. We use the term "supervision" to include clinical oversight functions directed toward assuring the quality of clinical care whenever the anesthesiologist is not the sole anesthesia care provider. In our department, the supervision provided by each anesthesiologist working in operating rooms is evaluated each day by the CRNA(s) and anesthesiology resident(s) with whom they worked the previous day. The evaluations utilize the 9 questions developed by de Oliveira Filho for residents to assess anesthesiologist supervision. Each question is answered on a 4-point Likert scale (1 = never, 2 = rarely, 3 = frequently, and 4 = always). We evaluated the reliability and validity of the instrument when used in daily practice by CRNAs. The data set included all 7273 daily supervision scores and 1088 comments of 77 anesthesiologists provided by 49 CRNAs, as well as the 6246 scores and 681 comments provided by 62 residents, for dates of service between July 1, 2013, and June 30, 2014. Reliability of the instrument was assessed using its internal consistency. Content analysis was used to associate supervision scores (i.e., mean of the 9 answers) and presence of the verbs "see" or "saw" combined with negation in comments (e.g., "I did not see the anesthesiologist during the case(s) together"). Results are reported as the mean ± SE from among the 6 two-month periods. Supervision scores <2 were provided for 7.2% ± 0.4% of assessments and scores <3 were provided for 36.6% ± 1.1% of assessments, by 18.2 ± 0.9 and 34.0 ± 0.6 CRNAs, respectively (i.e., low scores were not attributable to just a few CRNAs or anesthesiologists). These frequencies were greater than for trainees (anesthesiology residents) (both P < 0.0001). No single question among the 9 questions in the supervision instrument explained CRNA supervision scores <2 (or <3) because of substantial (expected) interquestion correlation. Cronbach's alpha equaled 0.895 ± 0.003 among the 6 two-month periods. Among the CRNA evaluations that included a written comment, the Cronbach's alpha was 0.907 ± 0.003. Thus, like for anesthesiology residents, when used by CRNAs, the questions measured a one-dimensional attribute. The presence of a comment containing the action verb "see" or "saw," with the focus theme ("I did not see …"), increased the odds of a CRNA providing a supervision score <2 (odds ratio = 74.2, P = 0.0003) and supervision score <3 (odds ratio = 48.2, P < 0.0001). Limiting consideration to scores with comments, there too was an association between these words and a score <2 (odds ratio = 19.4, P = 0.0003) and a score <3 (odds ratio = 31.5, P < 0.0001). In Iowa, substantial anesthesiologist presence is not required for CRNA billing. More comments containing "see" or "saw" were made by CRNAs rather than residents (n = 75 [97.4%] versus n = 2 [2.6%], respectively, P < 0.0001), indicating face validity of the analysis. If some of the 9 questions were not perceived by the CRNAs as relevant to their interprofessional interactions, Cronbach's alpha would be low, not the 0.907 ± 0.003, above. Similarly, one or more of the individual questions would also not routinely be scored at its upper boundary of 4.0 ("always"). This was not so, being as the score was 4.0 for 24.9% ± 0.3% of the CRNA evaluations, and that score of 4.0 was more common than even the next most common combination of scores (P < 0.0001). The de Oliveira Filho supervision instrument was designed for use by residents. Our results show that the instrument also is reliable and valid when used by CRNAs. This is important given our previous finding that the CRNA:MD ratio had no correlation with the level of supervision provided.

Mediterranean Diet: Prevention of Colorectal Cancer

PubMed Central

Donovan, Micah G.; Selmin, Ornella I.; Doetschman, Tom C.; Romagnolo, Donato F.

2017-01-01

Colorectal cancer (CRC) is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma–carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD) is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern. PMID:29259973

Dynamics of the GB3 loop regions from MD simulation: how much of it is real?

PubMed

Li, Tong; Jing, Qingqing; Yao, Lishan

2011-04-07

A total of 1.1 μs of molecular dynamics (MD) simulations were performed to study the structure and dynamics of protein GB3. The simulation motional amplitude of the loop regions is generally overestimated in comparison with the experimental backbone N-H order parameters S(2). Two-state behavior is observed for several residues in these regions, with the minor state population in the range of 3-13%. Further inspection suggests that the (φ, ψ) dihedral angles of the minor states deviate from the GB3 experimental values, implying the existence of nonnative states. After fitting the MD trajectories of these residues to the NMR RDCs, the minor state populations are significantly reduced by at least 80%, suggesting that MD simulations are strongly biased toward the minor states, thus overestimating the dynamics of the loop regions. The optimized trajectories produce intra, sequential H(N)-H(α) RDCs and intra (3)J(HNHα) that are not included in the trajectories fitting for these residues that are closer to the experimental data. Unlike GB3, 0.55 μs MD simulations of protein ubiquitin do not show distinctive minor states, and the derived NMR order parameters are better converged. Our findings indicate that the artifacts of the simulations depend on the specific system studied and that one should be cautious interpreting the enhanced dihedral dynamics from long MD simulations.

Shear viscosity for dense plasmas by equilibrium molecular dynamics in asymmetric Yukawa ionic mixtures.

PubMed

Haxhimali, Tomorr; Rudd, Robert E; Cabot, William H; Graziani, Frank R

2015-11-01

We present molecular dynamics (MD) calculations of shear viscosity for asymmetric mixed plasma for thermodynamic conditions relevant to astrophysical and inertial confinement fusion plasmas. Specifically, we consider mixtures of deuterium and argon at temperatures of 100-500 eV and a number density of 10^{25} ions/cc. The motion of 30,000-120,000 ions is simulated in which the ions interact via the Yukawa (screened Coulomb) potential. The electric field of the electrons is included in this effective interaction; the electrons are not simulated explicitly. Shear viscosity is calculated using the Green-Kubo approach with an integral of the shear stress autocorrelation function, a quantity calculated in the equilibrium MD simulations. We systematically study different mixtures through a series of simulations with increasing fraction of the minority high-Z element (Ar) in the D-Ar plasma mixture. In the more weakly coupled plasmas, at 500 eV and low Ar fractions, results from MD compare very well with Chapman-Enskog kinetic results. In the more strongly coupled plasmas, the kinetic theory does not agree well with the MD results. We develop a simple model that interpolates between classical kinetic theories at weak coupling and the Murillo Yukawa viscosity model at higher coupling. This hybrid kinetics-MD viscosity model agrees well with the MD results over the conditions simulated, ranging from moderately weakly coupled to moderately strongly coupled asymmetric plasma mixtures.

Shear viscosity for dense plasmas by equilibrium molecular dynamics in asymmetric Yukawa ionic mixtures

NASA Astrophysics Data System (ADS)

Haxhimali, Tomorr; Rudd, Robert E.; Cabot, William H.; Graziani, Frank R.

2015-11-01

We present molecular dynamics (MD) calculations of shear viscosity for asymmetric mixed plasma for thermodynamic conditions relevant to astrophysical and inertial confinement fusion plasmas. Specifically, we consider mixtures of deuterium and argon at temperatures of 100-500 eV and a number density of 1025 ions/cc. The motion of 30 000-120 000 ions is simulated in which the ions interact via the Yukawa (screened Coulomb) potential. The electric field of the electrons is included in this effective interaction; the electrons are not simulated explicitly. Shear viscosity is calculated using the Green-Kubo approach with an integral of the shear stress autocorrelation function, a quantity calculated in the equilibrium MD simulations. We systematically study different mixtures through a series of simulations with increasing fraction of the minority high-Z element (Ar) in the D-Ar plasma mixture. In the more weakly coupled plasmas, at 500 eV and low Ar fractions, results from MD compare very well with Chapman-Enskog kinetic results. In the more strongly coupled plasmas, the kinetic theory does not agree well with the MD results. We develop a simple model that interpolates between classical kinetic theories at weak coupling and the Murillo Yukawa viscosity model at higher coupling. This hybrid kinetics-MD viscosity model agrees well with the MD results over the conditions simulated, ranging from moderately weakly coupled to moderately strongly coupled asymmetric plasma mixtures.

Three-dimensional photography for the evaluation of facial profiles in obstructive sleep apnoea.

PubMed

Lin, Shih-Wei; Sutherland, Kate; Liao, Yu-Fang; Cistulli, Peter A; Chuang, Li-Pang; Chou, Yu-Ting; Chang, Chih-Hao; Lee, Chung-Shu; Li, Li-Fu; Chen, Ning-Hung

2018-06-01

Craniofacial structure is an important determinant of obstructive sleep apnoea (OSA) syndrome risk. Three-dimensional stereo-photogrammetry (3dMD) is a novel technique which allows quantification of the craniofacial profile. This study compares the facial images of OSA patients captured by 3dMD to three-dimensional computed tomography (3-D CT) and two-dimensional (2-D) digital photogrammetry. Measurements were correlated with indices of OSA severity. Thirty-eight patients diagnosed with OSA were included, and digital photogrammetry, 3dMD and 3-D CT were performed. Distances, areas, angles and volumes from the images captured by three methods were analysed. Almost all measurements captured by 3dMD showed strong agreement with 3-D CT measurements. Results from 2-D digital photogrammetry showed poor agreement with 3-D CT. Mandibular width, neck perimeter size and maxillary volume measurements correlated well with the severity of OSA using all three imaging methods. Mandibular length, facial width, binocular width, neck width, cranial base triangle area, cranial base area 1 and middle cranial fossa volume correlated well with OSA severity using 3dMD and 3-D CT, but not with 2-D digital photogrammetry. 3dMD provided accurate craniofacial measurements of OSA patients, which were highly concordant with those obtained by CT, while avoiding the radiation associated with CT. © 2018 Asian Pacific Society of Respirology.

Fluid Intelligence Predicts Novel Rule Implementation in a Distributed Frontoparietal Control Network.

PubMed

Tschentscher, Nadja; Mitchell, Daniel; Duncan, John

2017-05-03

Fluid intelligence has been associated with a distributed cognitive control or multiple-demand (MD) network, comprising regions of lateral frontal, insular, dorsomedial frontal, and parietal cortex. Human fluid intelligence is also intimately linked to task complexity, and the process of solving complex problems in a sequence of simpler, more focused parts. Here, a complex target detection task included multiple independent rules, applied one at a time in successive task epochs. Although only one rule was applied at a time, increasing task complexity (i.e., the number of rules) impaired performance in participants of lower fluid intelligence. Accompanying this loss of performance was reduced response to rule-critical events across the distributed MD network. The results link fluid intelligence and MD function to a process of attentional focus on the successive parts of complex behavior. SIGNIFICANCE STATEMENT Fluid intelligence is intimately linked to the ability to structure complex problems in a sequence of simpler, more focused parts. We examine the basis for this link in the functions of a distributed frontoparietal or multiple-demand (MD) network. With increased task complexity, participants of lower fluid intelligence showed reduced responses to task-critical events. Reduced responses in the MD system were accompanied by impaired behavioral performance. Low fluid intelligence is linked to poor foregrounding of task-critical information across a distributed MD system. Copyright © 2017 Tschentscher et al.

Revisiting metatropic dysplasia: presentation of a series of 19 novel patients and review of the literature.

PubMed

Geneviève, D; Le Merrer, M; Feingold, J; Munnich, A; Maroteaux, P; Cormier-Daire, V

2008-04-15

Metatropic dysplasia (MD-OMIM: 156530 and 250600) is a rare chondrodysplasia characterized by short limbs with limitation and enlargement of joints and usually severe kyphoscoliosis, first described in 1893. Up until now, 81 other patients have been reported. The phenotypic variability of MD has led to a classification based on radiological anomalies dividing into three different types: a lethal autosomal recessive form, an autosomal recessive non-lethal form and a non-lethal autosomal dominant form with less severe radiographs manifestations and a better clinical outcome. Here, we report on clinical and radiological features of 19 novel MD patients. We describe new radiological features, including precocious calcification of hyoid and cricoid cartilage, irregular and squared-off calcaneal bones and severe hypoplasia of the anterior portion of first cervical vertebrae. In addition, the observation of an overlap between the autosomal recessive non-lethal form and the non-lethal autosomal dominant form, the rarity of sibship recurrences and the observation of vertical transmissions of MD in the literature argue in favor of an autosomal dominant mode of inheritance for all MD types. This hypothesis is reinforced by the use of the statistical single ascertainment method that rejects the hypothesis of an autosomal recessive mode of inheritance responsible for MD. Therefore, we propose that recurrence in sibs is due to gonadal mosaicism. Copyright 2008 Wiley-Liss, Inc.

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy

PubMed Central

Morse, C.I.; Smith, J.; Denny, A.; Tweedale, J.; Searle, N.D.; Winwood, K.; Onambele-Pearson, G.L.

2016-01-01

Objectives: To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). Methods: Participants included 11 Fascioscapulohumeral (FSH), 11 Becker’s (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross sectional area (TAACSA) was measured using B-mode ultrasound. Grip strength was measured in all but DMD. Results: Physical activity was lower in DMD, FSH and BeMD than CTRL (P<0.05), and lower in DMD than other MDs (P<0.01). T and Z scores were lower in DMD and Be than CTRL (DR, P<0.05); and lower in DMD than CTRL, LG, and FSH (MST, P<0.01). TAACSA and grip strength was 35-59% and 50-58% smaller in MD than CTRL, respectively (P<0.01). Within MD, BPAQ correlated with bone QUS measures (r=0.42-0.38, P<0.01). PASIPD correlated with grip strength (r=0.65, P<0.01) and TAACSA (r=0.46, P<0.01). Conclusion: Muscle size, strength, and bone health was lower in adult males with MD compared to adult males without MD, the extent of this is partially determined by physical activity. PMID:27973386

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy.

PubMed

Morse, C I; Smith, J; Denny, A; Tweedale, J; Searle, N D; Winwood, K; Onambele-Pearson, G L

2016-12-14

To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). Participants included 11 Fascioscapulohumeral (FSH), 11 Becker's (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross sectional area (TA ACSA ) was measured using B-mode ultrasound. Grip strength was measured in all but DMD. Physical activity was lower in DMD, FSH and BeMD than CTRL (P<0.05), and lower in DMD than other MDs (P<0.01). T and Z scores were lower in DMD and Be than CTRL (DR, P<0.05); and lower in DMD than CTRL, LG, and FSH (MST, P<0.01). TA ACSA and grip strength was 35-59% and 50-58% smaller in MD than CTRL, respectively (P<0.01). Within MD, BPAQ correlated with bone QUS measures (r=0.42-0.38, P<0.01). PASIPD correlated with grip strength (r=0.65, P<0.01) and TA ACSA (r=0.46, P<0.01). Muscle size, strength, and bone health was lower in adult males with MD compared to adult males without MD, the extent of this is partially determined by physical activity.

The Relationship of Deiodinase 1 Genotype and Thyroid Function to Lifetime History of Major Depression in Three Independent Populations

PubMed Central

Philibert, Robert A.; Beach, Steven R. H.; Gunter, Tracy D.; Todorov, Alexandre A.; Brody, Gene H.; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-01-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime major depression and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone (TSH), free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3’ UTR of DIO1 (rs11206244), were associated with altered free thyroxine (FT4) levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. PMID:21563302

[Pathological and biochemical studies of 30 Niigata autopsy cases related to Minamata disease].

PubMed

Eto, Komyo; Takahashi, Hitoshi; Kakita, Akiyoshi; Tokunaga, Hidehiro; Yasutake, Akira; Nakano, Atsuhiro; Sawada, Masumi; Kinjo, Yoshihide

2007-01-01

To reevaluate pathologically and biochemically 30 autopsy cases related to Minamata disease (MD) in Niigata Prefecture (NP) and compare the findings with those of autopsy cases related to MD in Kumamoto Prefecture (KP). Recently, a set of pathological materials of these 30 autopsy cases has been sent from the Brain Research Institute at the University of Niigata to the National Institute for Minamata Disease (NIMD). The materials from each autopsy case were reexamined at the NIMD. There were no postnatal and fetal cases of MD in the NP autopsy materials. The contents of total mercury (T-Hg), methylmercury (Me-Hg), inorganic mercury (I-Hg) and selenium were measured in the organs of cerebrum, cerebellum, liver and kidney. The contents of T-Hg, Me-Hg and I-Hg were much higher in two cases than in controls. The pathological findings leading to the diagnosis of MD in the NP cases were essentially the same as those in KP, including the peripheral nerve lesions. In the most severely affected case of MD in NP, formation of multiple vacuoles of various sizes was observed in the cerebellar cortex, which was never encountered in the KP cases. The KP lesions were similar to that observed in an acute case of Me-Hg-treated common marmoset studied in the NIMD. The pathological features were essentially the same between the adult cases of MD in NP and KP.

Surgical physician assistants help solve contemporary problems.

PubMed

Blumm, Robert M; Condit, Doug

2003-06-01

Recent surveys performed by the AAPA estimate that in 2002 approximately 183 million visits were made to PAs and 223 million medications were prescribed or recommended by PAs. The AAPA estimates that just more than 46,000 PAs currently are in clinical practice, with New York and California having the largest numbers of practicing PAs. Helen Keller said, "The most pathetic person in the world is the person who has sight but no vision." Most individuals accept life and its shortcomings, but visionaries are different. They see not only that which is evident, but also that which exists in imagination. Visionary physicians and surgeons who aided in the creation of the physician assistant and use of PAs in surgery include: Eugene Stead, MD; John Kirklin, MD, FACS; E. Harvey Estes, Jr., MD; Richard Smith, MD, FACS; and Marvin Giledman, MD. They believed that well-educated nonphysicians could work alongside physicians as a team and, thus, expand the delivery of health care in America. PAs have crossed into the new millennium with new challenges. Together, as a team with supervising surgeons, PAs can meet the challenges and establish new alliances that will alleviate today's constraints. As Rear Adm. Kenneth P. Moritsugu, MD, MPH, Deputy Surgeon General, said, "Physician assistants are ideal partners and professionals in the nation's health system. They are colleagues with physicians to assure improved access to quality health care in a cost-effective manner.

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The effect of exercise training on clinical outcomes in patients with the metabolic syndrome: a systematic review and meta-analysis.

PubMed

Ostman, C; Smart, N A; Morcos, D; Duller, A; Ridley, W; Jewiss, D

2017-08-30

Purpose: to establish if exercise training improves clinical outcomes in people with metabolic syndrome (MetS). Registered with PROSPERO international prospective register of systematic reviews ( https://www.crd.york.ac.uk/PROSPERO/Identifier:CRD42017055491 ). studies were identified through a MEDLINE search strategy (1985 to Jan 12, 2017), Cochrane controlled trials registry, CINAHL and SPORTDiscus. prospective randomized or controlled trials of exercise training in humans with metabolic syndrome, lasting 12 weeks or more. We included 16 studies with 23 intervention groups; 77,000 patient-hours of exercise training. In analyses of aerobic exercise studies versus control: body mass index was significantly reduced, mean difference (MD) -0.29 (kg m -2 ) (95% CI -0.44, -0.15, p < 0.0001); body mass was significantly reduced, MD -1.16 kg (95% CI -1.83, -0.48, p = 0.0008); waist circumference was significantly reduced MD -1.37 cm (95% CI -2.02, -0.71, p < 0.0001), peak VO 2 was significantly improved MD 3.00 mL kg -1  min -1 (95% CI 1.92, 4.08, p < 0.000001); systolic blood pressure and diastolic blood pressure were significantly reduced, MD -2.54 mmHg (95% CI -4.34, -0.75, p = 0.006), and, MD -2.27 mmHg (95% CI -3.47, -1.06, p = 0.0002) respectively; fasting blood glucose was significantly reduced MD -0.16 mmol L -1 (95% CI -0.32, -0.01, p = 0.04); triglycerides were significantly reduced MD -0.21 mmol L -1 (95% CI -0.29, -0.13, p < 0.00001); and low density lipoprotein was significantly reduced MD -0.03 mmol L -1 (95% CI -0.05, -0.00, p = 0.02). In analyses of combined exercise versus control: waist circumference, MD -3.80 cm (95% CI -5.65, -1.95, p < 0.0001); peak VO 2 MD 4.64 mL kg -1  min -1 (95% CI 2.42, 6.87, p < 0.0001); systolic blood pressure MD -3.79 mmHg (95% CI -6.18, -1.40, p = 0.002); and high density lipoprotein (HDL) MD 0.14 (95% CI 0.04, 0.25, p = 0.009) were all significantly improved. We found no significant differences between outcome measures between the two exercise interventions. Exercise training improves body composition, cardiovascular, and, metabolic outcomes in people with metabolic syndrome. For some outcome measures, isolated aerobic exercise appears optimal.

Characterization of DTI Indices in the Cervical, Thoracic, and Lumbar Spinal Cord in Healthy Humans

PubMed Central

Bosma, Rachael L.; Stroman, Patrick W.

2012-01-01

The aim of this study was to characterize in vivo measurements of diffusion along the length of the entire healthy spinal cord and to compare DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), between cord regions. The objective is to determine whether or not there are significant differences in DTI indices along the cord that must be considered for future applications of characterizing the effects of injury or disease. A cardiac gated, single-shot EPI sequence was used to acquire diffusion-weighted images of the cervical, thoracic, and lumbar regions of the spinal cord in nine neurologically intact subjects (19 to 22 years). For each cord section, FA versus MD values were plotted, and a k-means clustering method was applied to partition the data according to tissue properties. FA and MD values from both white matter (average FA = 0.69, average MD = 0.93 × 10−3 mm2/s) and grey matter (average FA = 0.44, average MD = 1.8 × 10−3 mm2/s) were relatively consistent along the length of the cord. PMID:22295179

Contribution of Equal-Sign Instruction beyond Word-Problem Tutoring for Third-Grade Students with Mathematics Difficulty

PubMed Central

Powell, Sarah R.; Fuchs, Lynn S.

2010-01-01

Elementary school students often misinterpret the equal sign (=) as an operational rather than a relational symbol. Such misunderstanding is problematic because solving equations with missing numbers may be important for higher-order mathematics skills including word problems. Research indicates equal-sign instruction can alter how typically-developing students use the equal sign, but no study has examined effects for students with mathematics difficulty (MD) or how equal-sign instruction contributes to word-problem skill for students with or without MD. The present study assessed the efficacy of equal-sign instruction within word-problem tutoring. Third-grade students with MD (n = 80) were assigned to word-problem tutoring, word-problem tutoring plus equal-sign instruction (combined) tutoring, or no-tutoring control. Combined tutoring produced better improvement on equal sign tasks and open equations compared to the other 2 conditions. On certain forms of word problems, combined tutoring but not word-problem tutoring alone produced better improvement than control. When compared at posttest to 3rd-grade students without MD on equal sign tasks and open equations, only combined tutoring students with MD performed comparably. PMID:20640240

Molecular Dynamics Simulations, Challenges and Opportunities: A Biologist's Prospective.

PubMed

Kumari, Indu; Sandhu, Padmani; Ahmed, Mushtaq; Akhter, Yusuf

2017-08-30

Molecular dynamics (MD) is a computational technique which is used to study biomolecules in virtual environment. Each of the constituent atoms represents a particle and hence the biomolecule embodies a multi-particle mechanical system analyzed within a simulation box during MD analysis. The potential energies of the atoms are explained by a mathematical expression consisting of different forces and space parameters. There are various software and force fields that have been developed for MD studies of the biomolecules. MD analysis has unravelled the various biological mechanisms (protein folding/unfolding, protein-small molecule interactions, protein-protein interactions, DNA/RNA-protein interactions, proteins embedded in membrane, lipid-lipid interactions, drug transport etc.) operating at the atomic and molecular levels. However, there are still some parameters including torsions in amino acids, carbohydrates (whose structure is extended and not well defined like that of proteins) and single stranded nucleic acids for which the force fields need further improvement, although there are several workers putting in constant efforts in these directions. The existing force fields are not efficient for studying the crowded environment inside the cells, since these interactions involve multiple factors in real time. Therefore, the improved force fields may provide the opportunities for their wider applications on the complex biosystems in diverse cellular conditions. In conclusion, the intervention of MD in the basic sciences involving interdisciplinary approaches will be helpful for understanding many fundamental biological and physiological processes at the molecular levels that may be further applied in various fields including biotechnology, fisheries, sustainable agriculture and biomedical research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

How are Canadian universities training and supporting undergraduate medical, physiotherapy and occupational therapy students for global health experiences in international low-resource settings?

PubMed

Bessette, Jennifer; Camden, Chantal

2016-12-27

Canadian medical (MD), physiotherapy (PT) and occupational therapy (OT) students increasingly show an interest in global health experiences (GHEs). As certain moral hazards can occur as a result of student GHEs, a growing consensus exists that universities must have an established selection process, in-depth pre-departure training (PDT), adequate onsite supervision and formal debriefing for their students. This study aimed to identify current practices in Canadian MD, PT and OT programs and discuss areas for improvement by comparing them with recommendations found in the literature. Canadian MD, PT and OT programs (n = 45) were invited to answer an online survey about their current practices for GHE support and training. The survey included 24 close-ended questions and 18 open-ended questions. Descriptive statistics and a thematic analysis were performed on the data and results were discussed in comparison with recommendations found in the literature. Twenty-three programs responded to the survey. Student selection processes varied across universities; examples included using academic performance, interviews and motivation letters. All but one MD program had mandatory PDT; content and teaching formats varied, as did training duration (2-38 hours). All but one MD program had onsite supervision; local clinicians were frequently involved. Debriefing, although not systematic, covered similar content; debriefing was variable in duration (1-8 hours). Many current practices are encouraging, but areas for improvement exist. Integrating global health content into the regular curriculum, with advanced study options for students participating in GHEs, could help universities standardize support and training.

Douglas Lowy and Nirali Shah discuss advancements in cancer treatment at the second annual Chasing Cancer Summit | Center for Cancer Research

Cancer.gov

On Monday, September 18, 2017, the second annual Chasing Cancer Summit was held at the Washington Post headquarters in downtown Washington, D.C. The live event brought together a group of experts, including CCR’s Douglas Lowy, M.D., and Nirali Shah, M.D., for discussions on the latest developments in cancer detection and treatment.  Read more...

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Correlation between Macular Thickness and Visual Field in Early Open Angle Glaucoma: A Cross-Sectional Study.

PubMed

Fallahi Motlagh, Behzad; Sadeghi, Ali

2017-01-01

The aim of this study was to correlate macular thickness and visual field parameters in early glaucoma. A total of 104 eyes affected with early glaucoma were examined in a cross-sectional, prospective study. Visual field testing using both standard automated perimetry (SAP) and shortwave automated perimetry (SWAP) was performed. Global visual field parameters, including mean deviation (MD) and pattern standard deviation (PSD), were recorded and correlated with spectral domain optical coherence tomography (SD-OCT)-measured macular thickness and asymmetry. Average macular thickness correlated significantly with all measures of visual field including MD-SWAP (r = 0.42), MD-SAP (r = 0.41), PSD-SWAP (r = -0.23), and PSD-SAP (r = -0.21), with P-values <0.001 for all correlations. The mean MD scores (using both SWAP and SAP) were significantly higher in the eyes with thin than in those with intermediate average macular thickness. Intraeye (superior macula thickness - inferior macula thickness) asymmetries correlated significantly with both PSD-SWAP (r = 0.63, P < 0.001) and PSD-SAP (r = 0.26, P = 0.01) scores. This study revealed a significant correlation between macular thickness and visual field parameters in early glaucoma. The results of this study should make macular thickness measurements even more meaningful to glaucoma specialists.

Hierarchical Petascale Simulation Framework For Stress Corrosion Cracking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grama, Ananth

2013-12-18

A number of major accomplishments resulted from the project. These include: • Data Structures, Algorithms, and Numerical Methods for Reactive Molecular Dynamics. We have developed a range of novel data structures, algorithms, and solvers (amortized ILU, Spike) for use with ReaxFF and charge equilibration. • Parallel Formulations of ReactiveMD (Purdue ReactiveMolecular Dynamics Package, PuReMD, PuReMD-GPU, and PG-PuReMD) for Messaging, GPU, and GPU Cluster Platforms. We have developed efficient serial, parallel (MPI), GPU (Cuda), and GPU Cluster (MPI/Cuda) implementations. Our implementations have been demonstrated to be significantly better than the state of the art, both in terms of performance and scalability.more » • Comprehensive Validation in the Context of Diverse Applications. We have demonstrated the use of our software in diverse systems, including silica-water, silicon-germanium nanorods, and as part of other projects, extended it to applications ranging from explosives (RDX) to lipid bilayers (biomembranes under oxidative stress). • Open Source Software Packages for Reactive Molecular Dynamics. All versions of our soft- ware have been released over the public domain. There are over 100 major research groups worldwide using our software. • Implementation into the Department of Energy LAMMPS Software Package. We have also integrated our software into the Department of Energy LAMMPS software package.« less

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Hyperbaric hyperoxia alters innate immune functional properties during NASA Extreme Environment Mission Operation (NEEMO).

PubMed

Strewe, C; Crucian, B E; Sams, C F; Feuerecker, B; Stowe, R P; Choukèr, A; Feuerecker, M

2015-11-01

Spaceflight is associated with immune dysregulation which is considered as risk factor for the performance of exploration-class missions. Among the consequences of confinement and other environmental factors of living in hostile environments, the role of different oxygen concentrations is of importance as either low (e.g. as considered for lunar or Martian habitats) or high (e.g. during extravehicular activities) can trigger immune dysfunction. The aim of this study was to investigate the impact of increased oxygen availability--generated through hyperbaricity--on innate immune functions in the course of a 14 days NEEMO mission. 6 male subjects were included into a 14 days undersea deployment at the Aquarius station (Key Largo, FL, USA). The underwater habitat is located at an operating depth of 47 ft. The 2.5 times higher atmospheric pressure in the habitat leads to hyperoxia. The collection of biological samples occurred 6 days before (L-6), at day 7 (MD7) and 11/13 (MD11/13) during the mission, and 90 days thereafter (R). Blood analyses included differential blood cell count, ex vivo innate immune activation status and inhibitory competences of granulocytes. The absolute leukocyte count showed an increase during deployment as well as the granulocyte and monocyte count. Lymphocyte count was decreased on MD7. The assessments of native adhesion molecules on granulocytes (CD11b, CD62L) indicated a highly significant cellular activation (L-6 vs. MD7/MD13) during mission. In contrast, granulocytes were more sensitive towards anti-inflammatory stimuli (adenosine) on MD13. Living in the NEEMO habitat for 14 days induced significant immune alterations as seen by an activation of adhesion molecules and vice versa higher sensitivity towards inhibition. This investigation under hyperbaric hyperoxia is important especially for Astronauts' immune competence during extravehicular activities when exposed to similar conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

PARK7/DJ-1 dysregulation by oxidative stress leads to magnesium deficiency: implications in degenerative and chronic diseases.

PubMed

Kolisek, Martin; Montezano, Augusto C; Sponder, Gerhard; Anagnostopoulou, Aikaterini; Vormann, Juergen; Touyz, Rhian M; Aschenbach, Joerg R

2015-12-01

Disturbed magnesium (Mg(2+)) homoeostasis and increased levels of OS (oxidative stress) are associated with poor clinical outcomes in patients suffering from neurodegenerative, cardiovascular and metabolic diseases. Data from clinical and animal studies suggest that MD (Mg(2+) deficiency) is correlated with increased production of ROS (reactive oxygen species) in cells, but a straightforward causal relationship (including molecular mechanisms) between the two conditions is lacking. The multifactorial protein PARK7/DJ-1 is a major antioxidant protein, playing a key role in cellular redox homoeostasis, and is a positive regulator of AR (androgen receptor)-dependent transcription. SLC41A1 (solute carrier family 41 member 1), the gene encoding a ubiquitous cellular Mg(2+)E (Mg(2+)efflux) system, has been shown to be regulated by activated AR. We hypothesize that overexpression/up-regulation of PARK7/DJ-1, attributable to OS and related activation of AR, is an important event regulating the expression of SLC41A1 and consequently, modulating the Mg(2+)E capacity. This would involve changes in the transcriptional activity of PARK7/DJ-1, AR and SLC41A1, which may serve as biomarkers of intracellular MD and may have clinical relevance. Imipramine, in use as an antidepressant, has been shown to reduce the Mg(2+)E activity of SLC41A1 and OS. We therefore hypothesize further that administration of imipramine or related drugs will be beneficial in MD- and OS-associated diseases, especially when combined with Mg(2+) supplementation. If proved true, the OS-responsive functional axis, PARK7/DJ-1-AR-SLC41A1, may be a putative mechanism underlying intracellular MD secondary to OS caused by pro-oxidative stimuli, including extracellular MD. Furthermore, it will advance our understanding of the link between OS and MD. © 2015 Authors; published by Portland Press Limited.

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The Development of an Interactive Voice Response Survey for Noncommunicable Disease Risk Factor Estimation: Technical Assessment and Cognitive Testing

PubMed Central

Pereira, Amanda; Labrique, Alain B; Pariyo, George William

2017-01-01

Background The rise in mobile phone ownership in low- and middle-income countries (LMICs) presents an opportunity to transform existing data collection and surveillance methods. Administering surveys via interactive voice response (IVR) technology—a mobile phone survey (MPS) method—has potential to expand the current surveillance coverage and data collection, but formative work to contextualize the survey for LMIC deployment is needed. Objective The primary objectives of this study were to (1) cognitively test and identify challenging questions in a noncommunicable disease (NCD) risk factor questionnaire administered via an IVR platform and (2) assess the usability of the IVR platform. Methods We conducted two rounds of pilot testing the IVR survey in Baltimore, MD. Participants were included in the study if they identified as being from an LMIC. The first round included individual interviews to cognitively test the participant’s understanding of the questions. In the second round, participants unique from those in round 1 were placed in focus groups and were asked to comment on the usability of the IVR platform. Results A total of 12 participants from LMICs were cognitively tested in round 1 to assess their understanding and comprehension of questions in an IVR-administered survey. Overall, the participants found that the majority of the questions were easy to understand and did not have difficulty recording most answers. The most frequent recommendation was to use country-specific examples and units of measurement. In round 2, a separate set of 12 participants assessed the usability of the IVR platform. Overall, participants felt that the length of the survey was appropriate (average: 18 min and 31 s), but the majority reported fatigue in answering questions that had a similar question structure. Almost all participants commented that they thought an IVR survey would lead to more honest, accurate responses than face-to-face questionnaires, especially for sensitive topics. Conclusions Overall, the participants indicated a clear comprehension of the IVR-administered questionnaire and that the IVR platform was user-friendly. Formative research and cognitive testing of the questionnaire is needed for further adaptation before deploying in an LMIC. PMID:28476724

Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

PubMed

Kwan, Jennifer M; Daye, Dania; Schmidt, Mary Lou; Conlon, Claudia Morrissey; Kim, Hajwa; Gaonkar, Bilwaj; Payne, Aimee S; Riddle, Megan; Madera, Sharline; Adami, Alexander J; Winter, Kate Quinn

2017-07-11

Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy.

PubMed

Wu, Yuan; Yao, Xun; Vespasiani, Giacomo; Nicolucci, Antonio; Dong, Yajie; Kwong, Joey; Li, Ling; Sun, Xin; Tian, Haoming; Li, Sheyu

2017-03-14

Mobile health apps for diabetes self-management have different functions. However, the efficacy and safety of each function are not well studied, and no classification is available for these functions. The aims of this study were to (1) develop and validate a taxonomy of apps for diabetes self-management, (2) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of randomized controlled trials (RCTs), and (3) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy. We developed a 3-axis taxonomy with columns of clinical modules, rows of functional modules and cells of functions with risk assessments. This taxonomy was validated by reviewing and classifying commercially available diabetes apps. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database, and ClinicalTrials.gov from January 2007 to May 2016. We included RCTs of adult outpatients with diabetes that compared using mobile app-based interventions with usual care alone. The mean differences (MDs) in hemoglobin A 1c (HbA 1c ) concentrations and risk ratios of adverse events were pooled using a random-effects meta-analysis. After taxonomic classification, we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions. Across 12 included trials involving 974 participants, using app-based interventions was associated with a clinically significant reduction of HbA 1c (MD 0.48%, 95% CI 0.19%-0.77%) without excess adverse events. Larger HbA 1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes (MD 0.67%, 95% CI 0.30%-1.03% vs MD 0.36%, 95% CI 0.08%-0.81%). Having a complication prevention module in app-based interventions was associated with a greater HbA 1c reduction (with complication prevention: MD 1.31%, 95% CI 0.66%-1.96% vs without: MD 0.38%, 95% CI 0.09%-0.67%; intersubgroup P=.01), as was having a structured display (with structured display: MD 0.69%, 95% CI 0.32%-1.06% vs without: MD 0.16%, 95% CI 0.16%-0.48%; intersubgroup P=.03). However, having a clinical decision-making function was not associated with a larger HbA 1c reduction (with clinical decision making: MD 0.18%, 95% CI 0.21%-0.56% vs without: MD 0.61%, 95% CI 0.27%-0.95%; intersubgroup P=.10). The use of mobile app-based interventions yields a clinically significant HbA 1c reduction among adult outpatients with diabetes, especially among those with type 2 diabetes. Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps. ©Yuan Wu, Xun Yao, Giacomo Vespasiani, Antonio Nicolucci, Yajie Dong, Joey Kwong, Ling Li, Xin Sun, Haoming Tian, Sheyu Li. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 14.03.2017.

MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories.

PubMed

McGibbon, Robert T; Beauchamp, Kyle A; Harrigan, Matthew P; Klein, Christoph; Swails, Jason M; Hernández, Carlos X; Schwantes, Christian R; Wang, Lee-Ping; Lane, Thomas J; Pande, Vijay S

2015-10-20

As molecular dynamics (MD) simulations continue to evolve into powerful computational tools for studying complex biomolecular systems, the necessity of flexible and easy-to-use software tools for the analysis of these simulations is growing. We have developed MDTraj, a modern, lightweight, and fast software package for analyzing MD simulations. MDTraj reads and writes trajectory data in a wide variety of commonly used formats. It provides a large number of trajectory analysis capabilities including minimal root-mean-square-deviation calculations, secondary structure assignment, and the extraction of common order parameters. The package has a strong focus on interoperability with the wider scientific Python ecosystem, bridging the gap between MD data and the rapidly growing collection of industry-standard statistical analysis and visualization tools in Python. MDTraj is a powerful and user-friendly software package that simplifies the analysis of MD data and connects these datasets with the modern interactive data science software ecosystem in Python. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories

PubMed Central

McGibbon, Robert T.; Beauchamp, Kyle A.; Harrigan, Matthew P.; Klein, Christoph; Swails, Jason M.; Hernández, Carlos X.; Schwantes, Christian R.; Wang, Lee-Ping; Lane, Thomas J.; Pande, Vijay S.

2015-01-01

As molecular dynamics (MD) simulations continue to evolve into powerful computational tools for studying complex biomolecular systems, the necessity of flexible and easy-to-use software tools for the analysis of these simulations is growing. We have developed MDTraj, a modern, lightweight, and fast software package for analyzing MD simulations. MDTraj reads and writes trajectory data in a wide variety of commonly used formats. It provides a large number of trajectory analysis capabilities including minimal root-mean-square-deviation calculations, secondary structure assignment, and the extraction of common order parameters. The package has a strong focus on interoperability with the wider scientific Python ecosystem, bridging the gap between MD data and the rapidly growing collection of industry-standard statistical analysis and visualization tools in Python. MDTraj is a powerful and user-friendly software package that simplifies the analysis of MD data and connects these datasets with the modern interactive data science software ecosystem in Python. PMID:26488642

Anesthetic Management of a Child With Unspecified Mitochondrial Disease in an Outpatient Dental Setting.

PubMed

Gordon, Taylor R; Montandon, Richard J

2017-01-01

Mitochondrial disease (MD) represents a category of metabolic disorders with a wide range of symptoms across a variety of organ systems. It occurs with an incidence of greater than 1:5000 and can be difficult to specifically diagnose because of the variety of clinical presentations and multiple genomic origins. Although phenotypically variable, MD symptoms often include hypotonia, cardiac defects, dysautonomia, and metabolic dysfunction. Mitochondrial disease presents a unique challenge in terms of anesthetic management, as many anesthetic drugs suppress mitochondrial function. Additional considerations may need to be made in order to evaluate the patient's metabolic compensation prior to surgery. This article presents an in-depth discussion of a case involving a nearly 10-year-old boy with a history of an unspecified form of MD, who presented for endodontic treatment of tooth No. 30 under deep sedation. The article also provides a thorough review of the current literature surrounding the anesthetic management of patients with MD.

Fundamental Scaling of Microplasmas and Tunable UV Light Generation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manginell, Ronald P.; Sillerud, Colin Halliday; Hopkins, Matthew M.

2016-11-01

The temporal evolution of spectral lines from microplasma devices (MD) was studied, including impurity transitions. Long-wavelength emission diminishes more rapidly than deep UV with decreasing pulse width and RF operation. Thus, switching from DC to short pulsed or RF operation, UV emissions can be suppressed, allowing for real-time tuning of the ionization energy of a microplasma photo-ionization source, which is useful for chemical and atomic physics. Scaling allows MD to operate near atmospheric pressure where excimer states are efficiently created and emit down to 65 nm; laser emissions fall off below 200 nm, making MD light sources attractive for deepmore » UV use. A first fully-kinetic three-dimensional model was developed that explicitly calculates electron-energy distribution function. This, and non-continuum effects, were studied with the model and how they are impacted by geometry and transient or DC operation. Finally, a global non-dimensional model was developed to help explain general trends MD physics.« less

78 FR 49491 - Commission Information Collection Activities (FERC-574); Comment Request; Extension

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... State Commission is exercising that jurisdiction. 18 CFR Part 152 specifies the data required to be..., including salary + benefits. Comments: Comments are invited on: (1) Whether the collection of information is...

Numerical Simulations of Laser-Driven Microflyer Plates

NASA Astrophysics Data System (ADS)

Colvin, Jeffrey D.; Frank, Alan M.; Lee, Ronald S.; Remington, Bruce A.

2000-10-01

Experiments conducted in the US and France have accelerated few-micron-thick foils of aluminum to velocities of 3 - 5 km/s using 25 - 50 J/cm^2 of 1-μm laser light (1,2). These microflyer plates are not too dissimilar in size and velocity from interplanetary dust particles (3). We are performing numerical simulations of these experiments with the 2-D radiation-hydrodynamics code LASNEX (4), incorporating a model for low-fluence electromagnetic wave reflection and absorption in metals, with the objective of determining the physical processes important to optimizing the flyer design. We will discuss our preliminary findings, including the efficacy of a thermal insulation layer and the role played by the substrate on which the flyer is mounted. (1) W.M. Trott, R.E. Setchell, and A.V. Farnsworth, Jr., in Shock Compression of Condensed Matter-1999, ed. M.D. Furnish, L.C. Chhabildas, and R.S. Hixson, AIP, 2000, pp. 1203-06. (2) J. L. Labaste, M. Doucet, and P. Joubert, in Shock Compression of Condensed Matter-1995, ed. S.C. Schmidt and W.C. Tao, AIP, 1996, pp. 1221-24. (3) W.W. Anderson and T.J. Ahrens, J. Geophys. Res. 99, 2063 (1994). (4) G. B. Zimmerman and W. L. Kruer, Comments Plasma Phys. Controlled Fusion 2, 51 (1975).

Growth Failure in Children with Kidney Disease

MedlinePlus

... Ira Davis, M.D.; Ann Guillott, M.D.; Steve Alexander, M.D.; Deborah Kees-Folts, M.D.; Alicia Neu, M.D.; Steve Wassner, M.D.; John Brandt, M.D.; and ... Coordinating Committees Strategic Plans & Reports Research Areas FAQs Jobs at NIDDK Visit Us Contact Us News News ...

Long Term Hippocampal and Cortical Changes Induced by Maternal Deprivation and Neonatal Leptin Treatment in Male and Female Rats

PubMed Central

Mela, Virginia; Díaz, Francisca; Borcel, Erika; Argente, Jesús; Chowen, Julie A.; Viveros, Maria-Paz

2015-01-01

Maternal deprivation (MD) during neonatal life has diverse long-term behavioral effects and alters the development of the hippocampus and frontal cortex, with several of these effects being sexually dimorphic. MD animals show a marked reduction in their circulating leptin levels, not only during the MD period, but also several days later (PND 13). A neonatal leptin surge occurs in rodents (beginning around PND 5 and peaking between PND 9 and 10) that has an important neurotrophic role. We hypothesized that the deficient neonatal leptin signaling of MD rats could be involved in the altered development of their hippocampus and frontal cortex. Accordingly, a neonatal leptin treatment in MD rats would at least in part counteract their neurobehavioural alterations. MD was carried out in Wistar rats for 24 h on PND 9. Male and female MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg/day sc) or vehicle. In adulthood, the animals were submitted to the open field, novel object memory test and the elevated plus maze test of anxiety. Neuronal and glial population markers, components of the glutamatergic and cannabinoid systems and diverse synaptic plasticity markers were evaluated by PCR and/or western blotting. Main results include: 1) In some of the parameters analyzed, neonatal leptin treatment reversed the effects of MD (eg., mRNA expression of hippocampal IGF1 and protein expression of GFAP and vimentin) partially confirming our hypothesis; 2) The neonatal leptin treatment, per se, exerted a number of behavioral (increased anxiety) and neural effects (eg., expression of the following proteins: NG2, NeuN, PSD95, NCAM, synaptophysin). Most of these effects were sex dependent. An adequate neonatal leptin level (avoiding excess and deficiency) appears to be necessary for its correct neuro-programing effect. PMID:26382238

Final Environmental Assessment and Finding of No Significant Impact Proposed Running Track Hanscom AFB, Bedford, Massachusetts

DTIC Science & Technology

2004-09-01

agency response letters are included in Appendix B. Mr. Robert W. GoUedge, Jr. Commissioner, MADEP: No Comment Mr. Garry C. Waldeck MADEP...Headquarters: -Requested copy of Environmental Assessment ( No comment ). Mr. David Shakespeare MADEP - BWSC: No Comment Mr. James Sprague , ·. MADEP, NERO...Division of Watershed Management - Wetlands Program: No Comment · Mr. John Zajac MADEP, NERO Division ofWatershed Management: No Comment Mr. Todd

Teaching in small portions dispersed over time enhances long-term knowledge retention.

PubMed

Raman, Maitreyi; McLaughlin, Kevin; Violato, Claudio; Rostom, Alaa; Allard, J P; Coderre, Sylvain

2010-01-01

A primary goal of education is to promote long-term knowledge storage and retrieval. A prospective interventional study design was used to investigate our research question: Does a dispersed curriculum promote better short- and long-term retention over a massed course? Participants included 20 gastroenterology residents from the University of Calgary (N = 10) and University of Toronto (N = 10). Participants completed a baseline test of nutrition knowledge. The nutrition course was imparted to University of Calgary residents for 4 h occurring 1 h weekly over 4 consecutive weeks: dispersed delivery (DD). At the University of Toronto the course was taught in one 4h academic half-day: massed delivery (MD). Post-curriculum tests were administered at 1 week and 3 months to assess knowledge retention. The baseline scores were 46.39 +/- 6.14% and 53.75 +/- 10.69% in the DD and MD groups, respectively. The 1 week post-test scores for the DD and MD groups were 81.67 +/- 8.57%, p < 0.001 and 78.75 +/- 4.43, p < 0.001 which was significantly higher than baseline. The 3-month score was significantly higher in the DD group, but not in the MD group (65.28 +/- 9.88%, p = 0.02 vs. 58.93 +/- 12.06%, p = 0.18). The absolute pre-test to 1-week post-test difference was significantly higher at 35.28 +/- 7.65% among participants in the DD group compared to 25.0 +/- 11.80% in the MD group, p = 0.048. Similarly, the absolute pre-test to 3-month post-test difference was significantly higher at 18.9 +/- 6.7% among the participants in the DD group, compared to 6.8 +/- 11.8% in the MD group, p = 0.021. Long-term nutrition knowledge is improved with DD compared with MD.

Real-time fMRI neurofeedback of the mediodorsal and anterior thalamus enhances correlation between thalamic BOLD activity and alpha EEG rhythm.

PubMed

Zotev, Vadim; Misaki, Masaya; Phillips, Raquel; Wong, Chung Ki; Bodurka, Jerzy

2018-02-01

Real-time fMRI neurofeedback (rtfMRI-nf) with simultaneous EEG allows volitional modulation of BOLD activity of target brain regions and investigation of related electrophysiological activity. We applied this approach to study correlations between thalamic BOLD activity and alpha EEG rhythm. Healthy volunteers in the experimental group (EG, n = 15) learned to upregulate BOLD activity of the target region consisting of the mediodorsal (MD) and anterior (AN) thalamic nuclei using rtfMRI-nf during retrieval of happy autobiographical memories. Healthy subjects in the control group (CG, n = 14) were provided with a sham feedback. The EG participants were able to significantly increase BOLD activities of the MD and AN. Functional connectivity between the MD and the inferior precuneus was significantly enhanced during the rtfMRI-nf task. Average individual changes in the occipital alpha EEG power significantly correlated with the average MD BOLD activity levels for the EG. Temporal correlations between the occipital alpha EEG power and BOLD activities of the MD and AN were significantly enhanced, during the rtfMRI-nf task, for the EG compared to the CG. Temporal correlations with the alpha power were also significantly enhanced for the posterior nodes of the default mode network, including the precuneus/posterior cingulate, and for the dorsal striatum. Our findings suggest that the temporal correlation between the MD BOLD activity and posterior alpha EEG power is modulated by the interaction between the MD and the inferior precuneus, reflected in their functional connectivity. Our results demonstrate the potential of the rtfMRI-nf with simultaneous EEG for noninvasive neuromodulation studies of human brain function. © 2017 Wiley Periodicals, Inc.

Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign.

PubMed

Fendler, W; Borowiec, M; Baranowska-Jazwiecka, A; Szadkowska, A; Skala-Zamorowska, E; Deja, G; Jarosz-Chobot, P; Techmanska, I; Bautembach-Minkowska, J; Mysliwiec, M; Zmyslowska, A; Pietrzak, I; Malecki, M T; Mlynarski, W

2012-10-01

The aim of this study was to study dynamic changes in the prevalence of different types of diabetes in paediatric populations in Poland, with a specific focus on monogenic diabetes (MD). Using epidemiologic data (PolPeDiab Collaboration) and nationwide genetic test results (TEAM Programme), we compared the prevalence of type 1, type 2 and cystic fibrosis-related diabetes (CFRD) and MD. Genetically confirmed MD included MODY, neonatal diabetes and Wolfram and Alström syndromes. The study covered all children aged 0-18 years treated for diabetes between 2005 and 2011 in three regions, inhabited by 23.7% (1,989,988) of Polish children, with a low prevalence of childhood obesity (<5%). The prevalence of type 1 diabetes showed a continuous increase, from 96 to 138/100,000 children. The prevalence of type 2 diabetes and CFRD also increased, from 0.3 to 1.01/100,000 children and from 0.1 to 0.95/100,000 children, respectively. The prevalence of MD was stable at between 4.2 and 4.6/100,000 children, accounting for 3.1-4.2% of children with diabetes, with glucokinase (GCK)-MODY being the most frequent type, amounting to 83% of patients with MD. The percentage of positive test results decreased with the number of referrals, suggesting that children with the highest probability of MD were referred initially, followed by those with a less clear-cut phenotype. The prevalence of neonatal diabetes equalled 1 in 300,000 children. The prevalence of MD in a paediatric population with a low prevalence of obesity remains stable and is nearly fivefold higher than that of type 2 diabetes and CFRD, justifying a need for increased access to genetic diagnostic procedures in diabetic children.

Changes in cerebral metabolites in type 2 diabetes mellitus: A meta-analysis of proton magnetic resonance spectroscopy.

PubMed

Wu, Guang-Yao; Zhang, Qing; Wu, Jian-Lin; Jing, Li; Tan, Yang; Qiu, Tai-Chun; Zhao, Jiao

2017-11-01

To investigate whether there were differences and consistent patterns that highlight and consolidate the metabolite changes in type 2 diabetes mellitus (T2DM), a meta-analysis of proton magnetic resonance spectroscopy (MRS) was conducted. PubMed, Web of Science, and Embase databases were searched up to August 2016 for collecting the relevant studies. After an inclusion and exclusion criteria, the data was extracted. The data was analyzed using Stata software v.12.0. The weight mean difference (MD) and 95% confidence interval (CI) were used to compare continuous variables. A total of 10 studies (with a total of 244 T2DM patients and 223 healthy controls) were included. N-Acetyl Aspartate (NAA)/creatine (Cr) levels were decreased in the frontal lobe (MD=-0.20, 95%CI=-0.33 to -0.06, P=0.005) and lenticular nucleus (MD=-0.14, 95%CI=-0.22 to -0.06, P=0.001); choline (Cho)/Cr levels were increased in the lenticular nucleus (MD=0.15, 95%CI=0.02-0.28, P=0.025); myo-inositol (MI)/Cr levels were increased in the in the occipital lobe (MD=0.11, 95%CI=0.02-0.19, P=0.017) and parietal lobe (MD=0.16, 95%CI=0.05-0.28, P=0.006); MI levels were increased in the frontal white matter (MD=0.52, 95%CI=0.14-0.90, P=0.008). The results of our meta-analysis indicated that metabolite levels were altered in different regions of brain, which may be shown with MRS and caused clinical symptoms in T2DM further. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early social-communicative and cognitive development of younger siblings of children with autism spectrum disorders.

PubMed

Stone, Wendy L; McMahon, Caitlin R; Yoder, Paul J; Walden, Tedra A

2007-04-01

To compare the early social-communicative development of younger siblings of children with autism spectrum disorders (ASDs) with that of younger siblings of children with typical development, using parental report and child-based measures. Group comparison. Vanderbilt University, between July 1, 2003, and July 31, 2006. Younger siblings of children with ASD (n = 64) and younger siblings of children with typical development (n = 42) between the ages of 12 and 23 months (mean, 16 months). Main Exposure Having a sibling with an ASD. Child-based measures included a cognitive assessment; an interactive screening tool assessing play, imitation, and communication; and a rating of autism symptoms. Parental report measures were an interview of social-communicative interactions and a questionnaire assessing language and communication skills. Younger siblings of children with ASD demonstrated weaker performance in nonverbal problem solving (mean difference [MD], 5.91; 95% confidence interval [CI], 2.48-9.34), directing attention (MD, 0.52; 95% CI, 0.07-0.97), understanding words (MD, 33.30; 95% CI, 3.11-63.48), understanding phrases (MD, 4.56; 95% CI, 1.85-7.27), gesture use (MD, 1.49; 95% CI, 0.51-2.47), and social-communicative interactions with parents (MD, 1.32; 95% CI, 0.27-2.37), and had increased autism symptoms (MD, 2.54; 95% CI, 1.05-4.03), relative to control siblings. A substantial minority of the ASD sibling group exhibited lower performance relative to controls. Significant correlations between child-based measures and parental reports assessing similar constructs were found (r = -0.74 to 0.53; P range, .000-.002). The weaker performance found for children in the ASD sibling group may represent early-emerging features of the broader autism phenotype, thus highlighting the importance of developmental surveillance for younger siblings.

The relationship between childhood poverty, military service, and later life depression among men: Evidence from the Health and Retirement Study

PubMed Central

Bareis, Natalie; Mezuk, Briana

2017-01-01

Background Childhood poverty has been associated with depression in adulthood, but whether this relationship extends to later life major depression (MD) or is modified by military service is unclear. Methods Data come from the Health and Retirement Study (HRS) 2010 wave, a longitudinal, nationally representative study of older adults. Men with data on military service and childhood poverty were included (N = 6330). Childhood poverty was assessed by four indicators (i.e., parental unemployment, residential instability) experienced before age 16. Military service was categorized as veteran versus civilian, and during draft versus all-volunteer (after 1973) eras. Past year MD was defined by the Composite International Diagnostic Inventory. Results Four in ten men ever served, with 13.7% in the all-volunteer military. Approximately 12% of civilians, 8% draft era and 24% all-volunteer era veterans had MD. Childhood poverty was associated with higher odds of MD (Odds Ratio (OR): 2.38, 95% Confidence Interval (CI): 1.32–4.32) and higher odds of military service (OR: 2.58, 95% CI: 1.58–4.21). Military service was marginally associated with MD (OR: 1.28, 95% CI: 0.98–1.68) and did not moderate the association between childhood poverty and MD. Limitations Self-report data is subject to recall bias. The HRS did not assess childhood physical and emotional abuse, or military combat exposure. Conclusions Men raised in poverty had greater odds of draft and all-volunteer military service. Early-life experiences, independent of military service, appear associated with greater odds of MD. Assessing childhood poverty in service members may identify risk for depression in later life. PMID:27455351

Relationship between slow visual processing and reading speed in people with macular degeneration

PubMed Central

Cheong, Allen MY; Legge, Gordon E; Lawrence, Mary G; Cheung, Sing-Hang; Ruff, Mary A

2007-01-01

Purpose People with macular degeneration (MD) often read slowly even with adequate magnification to compensate for acuity loss. Oculomotor deficits may affect reading in MD, but cannot fully explain the substantial reduction in reading speed. Central-field loss (CFL) is often a consequence of macular degeneration, necessitating the use of peripheral vision for reading. We hypothesized that slower temporal processing of visual patterns in peripheral vision is a factor contributing to slow reading performance in MD patients. Methods Fifteen subjects with MD, including 12 with CFL, and five age-matched control subjects were recruited. Maximum reading speed and critical print size were measured with RSVP (Rapid Serial Visual Presentation). Temporal processing speed was studied by measuring letter-recognition accuracy for strings of three randomly selected letters centered at fixation for a range of exposure times. Temporal threshold was defined as the exposure time yielding 80% recognition accuracy for the central letter. Results Temporal thresholds for the MD subjects ranged from 159 to 5881 ms, much longer than values for age-matched controls in central vision (13 ms, p<0.01). The mean temporal threshold for the 11 MD subjects who used eccentric fixation (1555.8 ± 1708.4 ms) was much longer than the mean temporal threshold (97.0 ms ± 34.2 ms, p<0.01) for the age-matched controls at 10° in the lower visual field. Individual temporal thresholds accounted for 30% of the variance in reading speed (p<0.05). Conclusion The significant association between increased temporal threshold for letter recognition and reduced reading speed is consistent with the hypothesis that slower visual processing of letter recognition is one of the factors limiting reading speed in MD subjects. PMID:17881032

Allelic Variation in Paralogs of GDP-l-Galactose Phosphorylase Is a Major Determinant of Vitamin C Concentrations in Apple Fruit1[C][W][OA

PubMed Central

Mellidou, Ifigeneia; Chagné, David; Laing, William A.; Keulemans, Johan; Davey, Mark W.

2012-01-01

To identify the genetic factors underlying the regulation of fruit vitamin C (l-ascorbic acid [AsA]) concentrations, quantitative trait loci (QTL) studies were carried out in an F1 progeny derived from a cross between the apple (Malus × domestica) cultivars Telamon and Braeburn over three years. QTL were identified for AsA, glutathione, total antioxidant activity in both flesh and skin tissues, and various quality traits, including flesh browning. Four regions on chromosomes 10, 11, 16, and 17 contained stable fruit AsA-QTL clusters. Mapping of AsA metabolic genes identified colocations between orthologs of GDP-l-galactose phosphorylase (GGP), dehydroascorbate reductase (DHAR), and nucleobase-ascorbate transporter within these QTL clusters. Of particular interest are the three paralogs of MdGGP, which all colocated within AsA-QTL clusters. Allelic variants of MdGGP1 and MdGGP3 derived from the cultivar Braeburn parent were also consistently associated with higher fruit total AsA concentrations both within the mapping population (up to 10-fold) and across a range of commercial apple germplasm (up to 6-fold). Striking differences in the expression of the cv Braeburn MdGGP1 allele between fruit from high- and low-AsA genotypes clearly indicate a key role for MdGGP1 in the regulation of fruit AsA concentrations, and this MdGGP allele-specific single-nucleotide polymorphism marker represents an excellent candidate for directed breeding for enhanced fruit AsA concentrations. Interestingly, colocations were also found between MdDHAR3-3 and a stable QTL for browning in the cv Telamon parent, highlighting links between the redox status of the AsA pool and susceptibility to flesh browning. PMID:23001142

Associations of urinary 5-methyl-2'-deoxycytidine and 5-hydroxymethyl-2'-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men.

PubMed

Pan, Yitao; Jing, Jun; Yeung, Leo W Y; Sheng, Nan; Zhang, Hongxia; Yao, Bing; Dai, Jiayin

2016-09-01

5-methyl-2'-deoxycytidine (5mdC) and 5-hydroxymethyl-2'-deoxycytidine (5hmdC), products of DNA methylation and hydroxymethylation processes, have been detected previously in human urine, but their associations with environmental chemicals or healthy outcomes are unclear. The present investigation explored the associations between urinary 5mdC and 5hmdC with phthalate exposure and semen quality. We assessed semen parameters including sperm concentration, motility, and morphology, before measuring urinary 5mdC, 5hmdC and 13 phthalate metabolites among 562 subfertile men from Nanjing, China. Urinary 5mdC and 5hmdC were positively associated with the levels of low molecular weight phthalate metabolites (Low-MWP), high molecular weight phthalate metabolites (High-MWP), and the sum of all phthalate metabolites (ΣPAEs), respectively. Urinary 5mdC was associated with below-reference sperm concentration (odds ratios for increasing quartiles=1.0, 2.2, 3.0, 2.0; p for trend =0.02), sperm motility (1.0, 1.1, 1.9, 1.3; p for trend =0.05), and sperm morphology (1.0, 1.4, 2.3, 1.5; p for trend =0.05). Sperm concentration was associated with the highest quartile of urinary 5hmdC [odds ratio=1.9 (95% CI: 1.1, 3.6)]. Our findings showed significant associations between urinary 5mdC and 5hmdC with phthalate metabolites and semen parameters, which suggested urinary 5mdC and 5hmdC may be promising biomarkers in future epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Down-staging (

PubMed

Beukers, Willemien; Meijer, Titia; Vissers, Cornelis J; Boormans, Joost L; Zwarthoff, Ellen C; van Leenders, Geert J L H

2012-08-01

Urothelial cell carcinoma (UCC) with musculus detrusor (MD) invasion is treated by cystectomy. Subsequent pathologic evaluation of cystectomies does not reveal MD invasion (

Children with mathematical learning disability fail in recruiting verbal and numerical brain regions when solving simple multiplication problems.

PubMed

Berteletti, Ilaria; Prado, Jérôme; Booth, James R

2014-08-01

Greater skill in solving single-digit multiplication problems requires a progressive shift from a reliance on numerical to verbal mechanisms over development. Children with mathematical learning disability (MD), however, are thought to suffer from a specific impairment in numerical mechanisms. Here we tested the hypothesis that this impairment might prevent MD children from transitioning toward verbal mechanisms when solving single-digit multiplication problems. Brain activations during multiplication problems were compared in MD and typically developing (TD) children (3rd to 7th graders) in numerical and verbal regions which were individuated by independent localizer tasks. We used small (e.g., 2 × 3) and large (e.g., 7 × 9) problems as these problems likely differ in their reliance on verbal versus numerical mechanisms. Results indicate that MD children have reduced activations in both the verbal (i.e., left inferior frontal gyrus and left middle temporal to superior temporal gyri) and the numerical (i.e., right superior parietal lobule including intra-parietal sulcus) regions suggesting that both mechanisms are impaired. Moreover, the only reliable activation observed for MD children was in the numerical region when solving small problems. This suggests that MD children could effectively engage numerical mechanisms only for the easier problems. Conversely, TD children showed a modulation of activation with problem size in the verbal regions. This suggests that TD children were effectively engaging verbal mechanisms for the easier problems. Moreover, TD children with better language skills were more effective at engaging verbal mechanisms. In conclusion, results suggest that the numerical- and language-related processes involved in solving multiplication problems are impaired in MD children. Published by Elsevier Ltd.

Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia.

PubMed

Rutten-Jacobs, Loes C A; Tozer, Daniel J; Duering, Marco; Malik, Rainer; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew

2018-06-01

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance ( VCAN [versican]: rs13164785; P =3.7×10 -18 for MD and rs67827860; P =1.3×10 -14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE, 0.15]; MD-WMHV rG 0.56 [SE, 0.19]). In polygenic risk score analysis, FA, MD, and WMHV were significantly associated with lacunar stroke, MD with major depressive disorder, and WMHV with Alzheimer disease. Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD. Mechanisms underlying white matter alterations are shared with cerebrovascular disease, and inherited differences in white matter microstructure impact on Alzheimer disease and major depressive disorder. © 2018 The Authors.

Membrane fouling and wetting in membrane distillation and their mitigation by novel membranes with special wettability.

PubMed

Wang, Zhangxin; Lin, Shihong

2017-04-01

Membrane distillation (MD) has been identified as a promising technology to desalinate the hypersaline wastewaters from fracking and other industries. However, conventional hydrophobic MD membranes are highly susceptible to fouling and/or wetting by the hydrophobic and/or amphiphilic constituents in these wastewaters of complex compositions. This study systematically investigates the impact of the surface wetting properties on the membrane wetting and/or fouling behaviors in MD. Specifically, we compare the wetting and fouling resistance of three types of membranes of different wetting properties, including hydrophobic and omniphobic membranes as well as composite membranes with a hydrophobic substrate and a superhydrophilic top surface. We challenged the MD membranes with hypersaline feed solutions that contained a relatively high concentration of crude oil with and without added synthetic surfactants, Triton X-100. We found that the composite membranes with superhydrophilic top surface were robustly resistant to oil fouling in the absence of Triton X-100, but were subject to pore wetting in the presence of Triton X-100. On the other hand, the omniphobic membranes were easily fouled by oil-in-water emulsion without Triton X-100, but successfully sustained stable MD performance with Triton X-100 stabilized oil-in-water emulsion as the feed solution. In contrast, the conventional hydrophobic membranes failed readily regardless whether Triton X-100 was present, although via different mechanisms. These findings are corroborated by contact angle measures as well as oil-probe force spectroscopy. This study provides a holistic picture regarding how a hydrophobic membrane fails in MD and how we can leverage membranes with special wettability to prevent membrane failure in MD operations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Once-daily versus multiple-daily mesalamine for patients with ulcerative colitis: a meta-analysis.

PubMed

Tong, Jin Lu; Huang, Mei Lan; Xu, Xi Tao; Qiao, Yu Qi; Ran, Zhi Hua

2012-04-01

To systematically review the efficacy and safety of once-daily (OD) mesalamine for the treatment of ulcerative colitis (UC) compared with multiple-daily (MD) mesalamine. Electronic databases up to July 2011 were searched for related studies evaluating the efficacy of OD vs MD for treatment of UC. Only randomized controlled trials (RCTs) were considered eligible. Remission rates or relapse rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) analysis. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated. Publication bias was assessed with a funnel plot. Overall 10 RCTs including 9 full-text manuscripts and one abstract met the inclusion criteria. OD dosing of mesalamine was shown to be as effective as MD dosing for the maintenance of clinical remission in patients with quiescent UC (RR = 1.00, 95% CI 0.89-1.12) by ITT analysis. For active UC, a mild but significant benefit was achieved by OD dosing compared with MD dosing (RR = 0.80, 95% CI 0.64-0.99). Total adverse events were similar using OD and MD mesalamine in quiescent UC (RR = 1.06, 95% CI 0.93-1.20). Compliance with OD was slightly better than with MD (RR = 0.92, 95% CI 0.82-1.03). OD mesalamine is as effective and has a comparable safety profile as MD regimens for the maintenance treatment of UC, and is even more effective for inducing remission in active UC. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

The relationship between childhood poverty, military service, and later life depression among men: Evidence from the Health and Retirement Study.

PubMed

Bareis, Natalie; Mezuk, Briana

2016-12-01

Childhood poverty has been associated with depression in adulthood, but whether this relationship extends to later life major depression (MD) or is modified by military service is unclear. Data come from the Health and Retirement Study (HRS) 2010 wave, a longitudinal, nationally representative study of older adults. Men with data on military service and childhood poverty were included (N=6330). Childhood poverty was assessed by four indicators (i.e., parental unemployment, residential instability) experienced before age 16. Military service was categorized as veteran versus civilian, and during draft versus all-volunteer (after 1973) eras. Past year MD was defined by the Composite International Diagnostic Inventory. Four in ten men ever served, with 13.7% in the all-volunteer military. Approximately 12% of civilians, 8% draft era and 24% all-volunteer era veterans had MD. Childhood poverty was associated with higher odds of MD (Odds Ratio (OR): 2.38, 95% Confidence Interval (CI): 1.32-4.32) and higher odds of military service (OR: 2.58, 95% CI: 1.58-4.21). Military service was marginally associated with MD (OR: 1.28, 95% CI: 0.98-1.68) and did not moderate the association between childhood poverty and MD. Self-report data is subject to recall bias. The HRS did not assess childhood physical and emotional abuse, or military combat exposure. Men raised in poverty had greater odds of draft and all-volunteer military service. Early-life experiences, independent of military service, appear associated with greater odds of MD. Assessing childhood poverty in service members may identify risk for depression in later life. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of self-reported quality of sleep on mobility in older adults.

PubMed

Malinowska, Katarzyna B; Okura, Mika; Ogita, Mihoko; Yamamoto, Miki; Nakai, Toshimi; Numata, Tomoko; Tsuboyama, Tadao; Arai, Hidenori

2016-02-01

Quality of sleep (QOS) has been shown to have an affect on mental and physical well-being, and quality of life. However, few studies have investigated how sleep affects mobility in older adults. The aim of the present study was to examine the relationship between QOS and mobility disorder (MD) in community-dwelling older adults. Data collected through self-administered questionnaires was analyzed for 4564 Japanese older adults. Sleep outcomes included two self-reported questions regarding QOS. Logistic regression analysis was used to analyze the association between sleep and MD both by the QOS questions independently and grouped together by the two QOS questions into three groups: often sleeps well and good awakening (GG), does not often sleep well and bad awakening (BB) and a group with one of each (GB/BG). After adjustment for age, sex and depression, both those who did not often sleep well and those with poor awakening were more likely to show MD (OR 1.45, 95% CI 1.29-1.75), (OR 1.77, 95% CI 1.50-2.08), respectively. When grouped by both questions, those in the BB group had the least favorable outcome with increased odds ratio for possessing a MD (OR 1.95, 95% CI 1.61-2.37), compared with GB group (OR 1.40, 95% CI 1.18-1.67). Often sleeping well and good morning awakening were both associated with MD, suggesting that self reported QOS is associated with MD. Further research is required to investigate whether improving sleep quality could be a possible means of preventing and reversing MD in older adults. © 2015 Japan Geriatrics Society.

Epsilon aminocaproic acid reduces blood transfusion and improves the coagulation test after pediatric open-heart surgery: a meta-analysis of 5 clinical trials.

PubMed

Lu, Jun; Meng, Haoyu; Meng, Zhaoyi; Sun, Ying; Pribis, John P; Zhu, Chunyan; Li, Quan

2015-01-01

Excessive postoperative blood loss after cardiopulmonary bypass is a common problem, especially in patients suffering from congenital heart diseases. The efficacy of epsilon aminocaproic acid (EACA) as a prophylactic treatment for postoperative bleeding after pediatric open-heart surgery has not been determined. This meta-analysis investigates the efficacy of EACA in the minimization of bleeding and blood transfusion and the maintenance of coagulation tests after pediatric open-heart surgery. A comprehensive literature search was performed to identify all randomized clinical trials on the subject. PubMed, Embase, the Cochrane Library, and the Chinese Medical Journal Network were screened. The primary outcome used for the analysis was postoperative blood loss. Secondary outcomes included postoperative blood transfusion, re-exploration rate and postoperative coagulation tests. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were used as summary statistics. Five trials were included in this meta-analysis of 515 patients. Prophylactic EACA was associated with a reduction in postoperative blood loss, but this difference did not reach statistical significance (MD: -7.08; 95% CI: -16.11 to 1.95; P = 0.12). Patients treated with EACA received fewer postoperative blood transfusions, including packed red blood cells (MD: -8.36; 95% CI: -12.63 to -4.09; P = 0.0001), fresh frozen plasma (MD: -3.85; 95% CI: -5.63 to -2.08; P < 0.0001), and platelet concentrate (MD: -10.66; 95% CI: -18.45 to -2.87; P = 0.007), and had a lower re-exploration rate (RR: 0.46; 95% CI: 0.23 to 0.92; P = 0.03). Prophylactic EACA also improved coagulation tests 6 hours after open-heart surgery. Prophylactic EACA minimizes postoperative blood transfusion and helps maintain coagulation in pediatric patients undergoing open-heart surgery. Therefore, the results of this study indicate that adjunctive EACA is a good choice for the prevention of postoperative blood transfusion following pediatric cardiac surgery.

From force-fields to photons: MD simulations of dye-labeled nucleic acids and Monte Carlo modeling of FRET

NASA Astrophysics Data System (ADS)

Goldner, Lori

2012-02-01

Fluorescence resonance energy transfer (FRET) is a powerful technique for understanding the structural fluctuations and transformations of RNA, DNA and proteins. Molecular dynamics (MD) simulations provide a window into the nature of these fluctuations on a different, faster, time scale. We use Monte Carlo methods to model and compare FRET data from dye-labeled RNA with what might be predicted from the MD simulation. With a few notable exceptions, the contribution of fluorophore and linker dynamics to these FRET measurements has not been investigated. We include the dynamics of the ground state dyes and linkers in our study of a 16mer double-stranded RNA. Water is included explicitly in the simulation. Cyanine dyes are attached at either the 3' or 5' ends with a 3 carbon linker, and differences in labeling schemes are discussed.[4pt] Work done in collaboration with Peker Milas, Benjamin D. Gamari, and Louis Parrot.

Arthroscopic management of posterior instability of the shoulder: A systematic review of predictive factors associated with poorer surgical outcomes.

PubMed

Jain, Sachin Ramesh; Sayampanathan, Andrew Arjun; Hwee Chye Tan, Andrew

2017-01-01

We aimed to perform a systematic review to identify factors that may lead to poorer outcomes in arthroscopic surgery for posterior shoulder instability. We searched MEDLINE, Embase and the Cochrane Database of Systematic Reviews for 757 unique articles. We eventually included 22 articles. Data were analysed using Review Manager 5.3. The presence of chondral damage was associated with poorer outcomes as reflected in a higher post-operative Quick Disabilities of theArm, Shoulder and Hand score (mean difference (MD) = 17.1; 95% confidence interval (CI) = 2.82-31.4; p = 0.02), higher WesternOntario Shoulder Instability (WOSI) index (MD = 468.0; 95% CI = 136.5-799.5; p = 0.006), lower Simple Shoulder Test score (MD = -2.40; 95% CI = -4.34 to -0.46; p = 0.02) and a lower Single Assessment Numeric Evaluation score (MD = -15.4; 95% CI = -30.6 to -0.23; p = 0.05). The presence of previous shoulder surgery was associated with poorer outcomes as depicted by a lower American Shoulder and Elbow Society (ASES) score (MD = -93.1; 95% CI = -96.9 to -89.3; p < 0.0001). The availability of workers' compensation was associated with poorer outcomes as revealed by a lower rate of return to work (odds ratio (OR) = 0.02; 95% CI = 0.00-0.20; p = 0.0008). The presence of additional procedures while performing surgery for posterior shoulder instability was associated with poorer outcomes as reflected by lower ASES scores (MD = -6.70; 95% CI = -8.64 to -4.76; p < 0.0001), higher WOSI index (MD = 63.4; 95% CI = 33.0-93.8; p < 0.0001), lower University of California at Los Angeles (UCLA) scores (MD = -2.30; 95% CI = -2.81 to -1.79; p < 0.0001), higher pain scores (MD = 0.72; 95% CI = 0.39-1.05; p < 0.0001) and higher post-operative instability (MD = 0.80; 95% CI = 0.57-1.03; p < 0.0001). The presence of chondral damage, previous shoulder surgery, concomitant surgery and workman's compensation was associated with poorer outcomes for arthroscopic repair of posterior shoulder instability. Further studies should be done to further validate these factors.

Comparison of the short-term outcomes between delta-shaped anastomosis and conventional Billroth I anastomosis after laparoscopic distal gastrectomy: A meta-analysis.

PubMed

Ding, Wei; Tan, Yulin; Xue, Wenbo; Wang, Yibo; Xu, Xue-Zhong

2018-03-01

The conventional Billroth I anastomosis (cBIA) after laparoscopic distal gastrectomy (LDG) is performed through circular staple extracorporeally. Now, delta-shaped anastomosis (DA), which is performed using a linear stapler intracorporeally, becomes popular. We conducted a meta-analysis to compare the effectiveness and safety between the 2 techniques. A systematic literature search was performed using PubMed, Ovid, and the Cochrane Library Central. Participants of any age and sex, who underwent DA, or cBIA after LDG, were considered following inclusion criteria. A total of 11 articles, published between 2010 and 2017, fulfilled the selection criteria. The total sample size of these studies was 2729 cases, including DA group 1008 cases and cBIA group 1721 cases. Compared to cBIA group, patients in DA group had less blood loss (mean deviation [MD] = -0.68, 95% confidence interval [CI] = -0.15 to -0.31, P < .001), fewer administration of analgesics (MD = -0.82, 95% CI = -1.58 to -0.05, P = .04), lower NRS score on POD 1 (MD = -0.84, 95% CI = -1.34 to -0.33, P = .001), lower NRS score on POD 3 (MD = -0.38, 95% CI = -0.50 to -0.26, P < .001). Furthermore, compared to cBIA group, obese patients in DA group had fewer total number of complications (MD = 0.46, 95% CI = 0.22 to 0.95, P = .04), shorter postoperative hospital stays (MD = -0.73, 95% CI = -1.18 to -0.28, P = .001), earlier first flatus (MD = -0.30, 95% CI = -0.50 to -0.10, P = .004), fewer administration of analgesics (MD = -1.08, 95% CI = -1.61 to -0.55, P < .001), lower NRS score on POD 1 (MD = -0.68, 95% CI = -0.99 to -0.37, P < .001) and lower NRS score on POD 3 (MD = -0.63, 95% CI = -0.86 to -0.40, P < .001). Compared with cBIA, DA is a safe and feasible procedure, with similar surgical outcomes and postoperative complications. In terms of postoperative recovery, DA is less invasive with quicker resume than cBIA, especially for the obese patients.

Campanian ammonites from the Upper Cretaceous Gober Chalk of Lamar County, Texas

USGS Publications Warehouse

Cobban, W.A.; Kennedy, W.J.

1992-01-01

The Roxton Limestone Member at the top of the Gober Chalk in northeast Texas yields a rich fauna, dominated by Baculites haresi Reeside, 1927, and Inoceramus balticus Boehm, 1909, with sparse occurrences of pachydiscus cf. P. paulsoni (Young, 1963), Anapachydiscus sp.juv., Placenticeras placenta (DeKay, 1828), Hoplitoplacenticeras aff. H. plasticum (Paulcke, 1907), Menabites (Delawarella) delawarensis (Morton, 1830), M.(D.) danei (Young, 1963), M.(D.) aff. M.(D.) vanuxemi (Morton, 1830), Submortoniceras vandalinaense Young, 1963, Submortoniceras sp., Eubostrychoceras sp., and Scaphites hippocrepis (DeKay, 1828) III. The presence of S. hippocrepis III suggests a late early Campanian age assignment for the fauna. The assemblage includes species known from the Western Interior, Gulf Coast, Atlantic seaboard, and western Europe. -Authors

78 FR 21846 - Approval and Promulgation of State Plans for Designated Facilities and Pollutants: Connecticut...

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2013-04-12

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75 FR 39625 - Elimination of Flash Order Exception From Rule 602 of Regulation NMS

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2010-07-09

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78 FR 20099 - Duke Energy Carolinas, LLC; Notice of Application Accepted for Filing and Soliciting Comments...

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2013-04-03

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75 FR 65649 - Notice of Realty Action: Segregation To Consider Proposed Sale of Public Lands in Blaine County, ID

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

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78 FR 8502 - Appalachian Power Company; Notice of Application for Amendment of License and Soliciting Comments...

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2013-02-06

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77 FR 50508 - Brain-Pad, Inc; Analysis of Proposed Consent Order To Aid Public Comment

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2012-08-21

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

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Cloth Ballistic Vest Alters Response to Blast

DTIC Science & Technology

1988-01-01

Detrick, Frederick, MD 21701-501 ELEMENT NO. NO. NO. jACCESSION NO. 11. TITLE (include Security Classification) CLOTH BALLSISTIC VEST ALTERS RESPONSE...Suppl. ’rintd in USA Cloth Ballistic Vest Alters Response to Blast YANCY Y. PHILLIPS, M.D., THOMAS G. MUNDIE, PH.D., JOHN T. YELVERTON, M.S., AND DONALD R...RICHMOND, PH.D. Ballistic wounds have been and will remain the principal cause of casualties in combat. Cloth ballistic vests (CBV) play an

Multivariate missing data in hydrology - Review and applications

NASA Astrophysics Data System (ADS)

Ben Aissia, Mohamed-Aymen; Chebana, Fateh; Ouarda, Taha B. M. J.

2017-12-01

Water resources planning and management require complete data sets of a number of hydrological variables, such as flood peaks and volumes. However, hydrologists are often faced with the problem of missing data (MD) in hydrological databases. Several methods are used to deal with the imputation of MD. During the last decade, multivariate approaches have gained popularity in the field of hydrology, especially in hydrological frequency analysis (HFA). However, treating the MD remains neglected in the multivariate HFA literature whereas the focus has been mainly on the modeling component. For a complete analysis and in order to optimize the use of data, MD should also be treated in the multivariate setting prior to modeling and inference. Imputation of MD in the multivariate hydrological framework can have direct implications on the quality of the estimation. Indeed, the dependence between the series represents important additional information that can be included in the imputation process. The objective of the present paper is to highlight the importance of treating MD in multivariate hydrological frequency analysis by reviewing and applying multivariate imputation methods and by comparing univariate and multivariate imputation methods. An application is carried out for multiple flood attributes on three sites in order to evaluate the performance of the different methods based on the leave-one-out procedure. The results indicate that, the performance of imputation methods can be improved by adopting the multivariate setting, compared to mean substitution and interpolation methods, especially when using the copula-based approach.

Multicomponent Lifestyle Interventions for Treating Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analyses

PubMed Central

Giske, L.; Fure, B.; Juvet, L. K.

2017-01-01

Background Treatment of childhood obesity is important in preventing development of obesity-related diseases later in life. This systematic review evaluates the effect of multicomponent lifestyle interventions for children and adolescents from 2 to 18 years. Methods and Results We performed systematic searches in nine databases. Thirty-nine studies met the criteria for meta-analyses. We found a significant difference in body mass index (BMI) after 6 months (MD −0.99 (95% CI −1.36 to −0.61)), 12 months (MD −0.67 (95% CI −1.01 to −0.32)), and 24 months (MD −0.96 (95% CI −1.63 to −0.29)) in favour of multicomponent lifestyle interventions compared to standard, minimal, and no treatment. We also found a significant difference in BMI Z scores after 6 months (MD −0.12 (95% CI −0.17 to −0.06)), 12 months (MD −0.16 (95% CI −0.21 to −0.11)), and 24 months (MD −0.16 (95% CI −0.21 to −0.10)) in favour of multicomponent lifestyle interventions. Subgroup analyses suggested an increased effect in specialist health care with a group treatment component included in the intervention. Conclusion Multicomponent lifestyle interventions have a moderate effect on change in BMI and BMI Z score after 6, 12, and 24 months compared with standard, minimal, and no treatment. PMID:29391949

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy.

PubMed

La Torre, Giuseppe; Saulle, Rosella; Di Murro, Francesca; Siliquini, Roberta; Firenze, Alberto; Maurici, Massimo; Mannocci, Alice; Colamesta, Vittoria; Barillà, Francesco; Ferrante, Fabio; Agati, Luciano

2018-01-01

Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Case-control study. Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits.

The Weather and Ménière's Disease: A Longitudinal Analysis in the UK.

PubMed

Schmidt, Wiebke; Sarran, Christophe; Ronan, Natalie; Barrett, George; Whinney, David J; Fleming, Lora E; Osborne, Nicholas J; Tyrrell, Jessica

2017-02-01

Changes in the weather influence symptom severity in Ménière's disease (MD). MD is an unpredictable condition that significantly impacts on quality of life. It is suggested that fluctuations in the weather, especially atmospheric pressure may influence the symptoms of MD. However, to date, limited research has investigated the impact of the weather on MD. In a longitudinal study, a mobile phone application collected data from 397 individuals (277 females and 120 males with an average age of 50 yr) from the UK reporting consultant-diagnosed MD. Daily symptoms (vertigo, aural fullness, tinnitus, hearing loss, and attack prevalence) and GPS locations were collected; these data were linked with Met Office weather data (including atmospheric pressure, humidity, temperature, visibility, and wind speed). Symptom severity and attack prevalence were reduced on days when atmospheric pressure was higher. When atmospheric pressure was below 1,013 hectopascals, the risk of an attack was 1.30 (95% confidence interval: 1.10, 1.54); when the humidity was above 90%, the risk of an attack was 1.26 (95% confidence interval 1.06, 1.49). This study provides the strongest evidence to date that changes in atmospheric pressure and humidity are associated with symptom exacerbation in MD. Improving our understanding of the role of weather and other environmental triggers in Ménière's may reduce the uncertainty associated with living with this condition, significantly contributing to improved quality of life.

The Weather and Ménière’s Disease: A Longitudinal Analysis in the UK

PubMed Central

Schmidt, Wiebke; Sarran, Christophe; Ronan, Natalie; Barrett, George; Whinney, David J.; Fleming, Lora E.; Osborne, Nicholas J.; Tyrrell, Jessica

2016-01-01

Hypothesis Changes in the weather influence symptom severity in Ménière’s disease (MD). Background MD is an unpredictable condition that significantly impacts on quality of life. It is suggested that fluctuations in the weather, especially atmospheric pressure may influence the symptoms of MD. However, to date, limited research has investigated the impact of the weather on MD. Methods In a longitudinal study, a mobile phone application collected data from 397 individuals (277 females and 120 males with an average age of 50 yr) from the UK reporting consultant-diagnosed MD. Daily symptoms (vertigo, aural fullness, tinnitus, hearing loss, and attack prevalence) and GPS locations were collected; these data were linked with Met Office weather data (including atmospheric pressure, humidity, temperature, visibility, and wind speed). Results Symptom severity and attack prevalence were reduced on days when atmospheric pressure was higher. When atmospheric pressure was below 1,013 hectopascals, the risk of an attack was 1.30 (95% confidence interval: 1.10, 1.54); when the humidity was above 90%, the risk of an attack was 1.26 (95% confidence interval 1.06, 1.49). Conclusion This study provides the strongest evidence to date that changes in atmospheric pressure and humidity are associated with symptom exacerbation in MD. Improving our understanding of the role of weather and other environmental triggers in Ménière’s may reduce the uncertainty associated with living with this condition, significantly contributing to improved quality of life. PMID:27861300

Shear viscosity for dense plasmas by equilibrium molecular dynamics in asymmetric Yukawa ionic mixtures

DOE PAGES

Haxhimali, Tomorr; Rudd, Robert E.; Cabot, William H.; ...

2015-11-24

We present molecular dynamics (MD) calculations of shear viscosity for asymmetric mixed plasma for thermodynamic conditions relevant to astrophysical and inertial confinement fusion plasmas. Specifically, we consider mixtures of deuterium and argon at temperatures of 100–500 eV and a number density of 10 25 ions/cc. The motion of 30 000–120 000 ions is simulated in which the ions interact via the Yukawa (screened Coulomb) potential. The electric field of the electrons is included in this effective interaction; the electrons are not simulated explicitly. Shear viscosity is calculated using the Green-Kubo approach with an integral of the shear stress autocorrelation function,more » a quantity calculated in the equilibrium MD simulations. We systematically study different mixtures through a series of simulations with increasing fraction of the minority high- Z element (Ar) in the D-Ar plasma mixture. In the more weakly coupled plasmas, at 500 eV and low Ar fractions, results from MD compare very well with Chapman-Enskog kinetic results. In the more strongly coupled plasmas, the kinetic theory does not agree well with the MD results. Here, we develop a simple model that interpolates between classical kinetic theories at weak coupling and the Murillo Yukawa viscosity model at higher coupling. Finally, this hybrid kinetics-MD viscosity model agrees well with the MD results over the conditions simulated, ranging from moderately weakly coupled to moderately strongly coupled asymmetric plasma mixtures.« less

Global and regional brain mean diffusivity changes in patients with heart failure.

PubMed

Woo, Mary A; Palomares, Jose A; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

2015-04-01

Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P < 0.001; right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue changes likely result from processes that develop over a prolonged period. © 2014 Wiley Periodicals, Inc.

Acupoint stimulation, massage therapy and expressive writing for breast cancer: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Lee, Phoebe Lyssandra Tan; Tam, Ka-Wai; Yeh, Mei-Ling; Wu, Wei-Wen

2016-08-01

Researches have accumulated using non-pharmacologic interventions including acupoint stimulation, massage therapy and expressive writing to manage breast cancer-related symptoms. Results from randomized controlled trials (RCTs) can get contradictory. A systematic review and meta-analysis were conducted to determine the effects on the quality of life, negative emotions and disease-related symptoms among women with breast cancer. Two independent researchers performed a structured search using data sources including MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, PubMed and PsychINFO from the beginning of time until the first week of January 2015. A total of 23 acupoint stimulation, massage therapy and expressive writing RCTs were included in the review. The study showed that no single intervention could be put under the spotlight exhibiting an overall effective result on all measured outcomes; however, looking into each one in detail shows different results in specific outcomes. Among the three interventions, acupoint stimulation has a treatment effect for general pain (MD=-1.46, 95% CI=-2.38 to -0.53) and fatigue (MD=-2.22, 95% CI=-3.68 to -0.77), massage therapy has a treatment effect for anxiety (MD=-0.50, 95% CI=-0.77 to -0.24), and expressive writing has a treatment effect for quality of life (MD=7.18, 95% CI=0.38 to 13.98). The measurement other outcomes showed either ineffective or equivocal results. Non-pharmacologic interventions including acupoint stimulation, massage therapy and expressive writing have an effect on a middle-age woman with breast cancer. However, because of limitations, the seemingly promising results should be interpreted with caution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apple (Malus domestica) MdERF2 negatively affects ethylene biosynthesis during fruit ripening by suppressing MdACS1 transcription.

PubMed

Li, Tong; Jiang, Zhongyu; Zhang, Lichao; Tan, Dongmei; Wei, Yun; Yuan, Hui; Li, Tianlai; Wang, Aide

2016-12-01

Ripening in climacteric fruit requires the gaseous phytohormone ethylene. Although ethylene signaling has been well studied, knowledge of the transcriptional regulation of ethylene biosynthesis is still limited. Here we show that an apple (Malus domestica) ethylene response factor, MdERF2, negatively affects ethylene biosynthesis and fruit ripening by suppressing the transcription of MdACS1, a gene that is critical for biosynthesis of ripening-related ethylene. Expression of MdERF2 was suppressed by ethylene during ripening of apple fruit, and we observed that MdERF2 bound to the promoter of MdACS1 and directly suppressed its transcription. Moreover, MdERF2 suppressed the activity of the promoter of MdERF3, a transcription factor that we found to bind to the MdACS1 promoter, thereby increasing MdACS1 transcription. We determined that the MdERF2 and MdERF3 proteins directly interact, and this interaction suppresses the binding of MdERF3 to the MdACS1 promoter. Moreover, apple fruit with transiently downregulated MdERF2 expression showed higher ethylene production and faster ripening. Our results indicate that MdERF2 negatively affects ethylene biosynthesis and fruit ripening in apple by suppressing the transcription of MdACS1 via multiple mechanisms, thereby acting as an antagonist of positive ripening regulators. Our findings offer a deep understanding of the transcriptional regulation of ethylene biosynthesis during climacteric fruit ripening. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Understanding Public Perceptions of the HPV Vaccination Based on Online Comments to Canadian News Articles

PubMed Central

Feinberg, Yael; Pereira, Jennifer A.; Quach, Susan; Kwong, Jeffrey C.; Crowcroft, Natasha S.; Wilson, Sarah E.; Guay, Maryse; Lei, Yang; Deeks, Shelley L.

2015-01-01

Background Given the variation in human papillomavirus (HPV) vaccine coverage across Canada, and debate regarding delivery of HPV vaccines in Catholic schools, we studied online comments on Canadian news websites to understand public perceptions of HPV and HPV vaccine. Methods We searched English- and French-language Canadian news websites for 2012 articles that contained the terms “HPV” or “human papillomavirus.” Articles about HPV vaccinations that contained at least one comment were included. Two researchers independently coded comments, analyzing them for emerging themes. Results We identified 3073 comments from 1198 individuals in response to 71 news articles; 630 (52.6%) individuals expressed positive sentiments about HPV vaccination (2.5 comments/individual), 404 (33.7%) were negative (3.0 comments/individual), 34 (2.8%) were mixed (1.5 comments/individual) and 130 (10.8%) were neutral (1.6 comments/individual). Vaccine-supportive commenters believed the vaccine is safe and effective. Common themes in negative comments included concerns regarding HPV vaccine safety and efficacy, distrust of pharmaceutical companies and government, and belief that school-age children are too young for HPV vaccine. Many comments focused on whether the Catholic Church has the right to inform health policy for students, and discussion often evolved into debates regarding HPV and sexual behaviour. We noted that many individuals doubted the credibility of vaccine safety information. Conclusion The majority of commenters do not appear to be against HPV vaccination, but public health messaging that focuses on both the vaccine’s safety profile, and its use as a means to prevent cancer rather than sexually transmitted HPV infection may facilitate its acceptance. PMID:26053866

Development of a templated approach to fabricate diamond patterns on various substrates.

PubMed

Shimoni, Olga; Cervenka, Jiri; Karle, Timothy J; Fox, Kate; Gibson, Brant C; Tomljenovic-Hanic, Snjezana; Greentree, Andrew D; Prawer, Steven

2014-06-11

We demonstrate a robust templated approach to pattern thin films of chemical vapor deposited nanocrystalline diamond grown from monodispersed nanodiamond (mdND) seeds. The method works on a range of substrates, and we herein demonstrate the method using silicon, aluminum nitride (AlN), and sapphire substrates. Patterns are defined using photo- and e-beam lithography, which are seeded with mdND colloids and subsequently introduced into microwave assisted chemical vapor deposition reactor to grow patterned nanocrystalline diamond films. In this study, we investigate various factors that affect the selective seeding of different substrates to create high quality diamond thin films, including mdND surface termination, zeta potential, surface treatment, and plasma cleaning. Although the electrostatic interaction between mdND colloids and substrates is the main process driving adherence, we found that chemical reaction (esterification) or hydrogen bonding can potentially dominate the seeding process. Leveraging the knowledge on these different interactions, we optimize fabrication protocols to eliminate unwanted diamond nucleation outside the patterned areas. Furthermore, we have achieved the deposition of patterned diamond films and arrays over a range of feature sizes. This study contributes to a comprehensive understanding of the mdND-substrate interaction that will enable the fabrication of integrated nanocrystalline diamond thin films for microelectronics, sensors, and tissue culturing applications.

[Research on outlier detection methods for determination of oil yield in oil shales using near-infrared spectroscopy].

PubMed

Zhang, Huai-zhu; Lin, Jun; Zhang, Huai-Zhu

2014-06-01

In the present paper, the outlier detection methods for determination of oil yield in oil shale using near-infrared (NIR) diffuse reflection spectroscopy was studied. During the quantitative analysis with near-infrared spectroscopy, environmental change and operator error will both produce outliers. The presence of outliers will affect the overall distribution trend of samples and lead to the decrease in predictive capability. Thus, the detection of outliers are important for the construction of high-quality calibration models. The methods including principal component analysis-Mahalanobis distance (PCA-MD) and resampling by half-means (RHM) were applied to the discrimination and elimination of outliers in this work. The thresholds and confidences for MD and RHM were optimized using the performance of partial least squares (PLS) models constructed after the elimination of outliers, respectively. Compared with the model constructed with the data of full spectrum, the values of RMSEP of the models constructed with the application of PCA-MD with a threshold of a value equal to the sum of average and standard deviation of MD, RHM with the confidence level of 85%, and the combination of PCA-MD and RHM, were reduced by 48.3%, 27.5% and 44.8%, respectively. The predictive ability of the calibration model has been improved effectively.

Ab Initio ONIOM-Molecular Dynamics (MD) Study on the Deamination Reaction by Cytidine Deaminase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

2007-08-23

We applied the ONIOM-molecular dynamics (MD) method to the hydrolytic deamination of cytidine by cytidine deaminase, which is an essential step of the activation process of the anticancer drug inside the human body. The direct MD simulations were performed for the realistic model of cytidine deaminase calculating the energy and its gradient by the ab initio ONIOM method on the fly. The ONIOM-MD calculations including the thermal motion show that the neighboring amino acid residue is an important factor of the environmental effects and significantly affects not only the geometry and energy of the substrate trapped in the pocket ofmore » the active site but also the elementary step of the catalytic reaction. We successfully simulate the second half of the catalytic cycle, which has been considered to involve the rate-determining step, and reveal that the rate-determing step is the release of the NH3 molecule. TM and MA were supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. MD was supported by the Division of Chemical Sciences, Office of Basic Energy Sciences, and by the Office of Biological and Environmental Research of the U.S. Department of Energy DOE. Battelle operates Pacific Northwest National Laboratory for DOE.« less

Single-session tDCS-supported retraining does not improve fine motor control in musician's dystonia.

PubMed

Buttkus, Franziska; Baur, Volker; Jabusch, Hans-Christian; de la Cruz Gomez-Pellin, Maria; Paulus, Walter; Nitsche, Michael A; Altenmüller, Eckart

2011-01-01

Focal dystonia in musicians (MD) is a task-specific movement disorder with a loss of voluntary motor control during instrumental playing. Defective inhibition on different levels of the central nervous system is involved in the pathophysiology. Sensorimotor retraining is a therapeutic approach to MD and aims to establish non-dystonic movements. Transcranial direct current stimulation (tDCS) modulates cortical excitability and alters motor performance. In this study, tDCS of the motor cortex was expected to assist retraining at the instrument. Nine professional pianists suffering from MD were included in a placebo-controlled double-blinded study. Retraining consisted of slow, voluntarily controlled movements on the piano and was combined with tDCS. Patients were treated with three stimulation protocols: anodal tDCS, cathodal tDCS and placebo stimulation. No beneficial effects of single-session tDCS-supported sensorimotor retraining on fine motor control in pianists with MD were found in all three conditions. The main cause of the negative result of this study may be the short intervention time. One retraining session with a duration of 20 min seems not sufficient to improve symptoms of MD. Additionally, a single tDCS session might not be sufficient to modify sensorimotor learning of a highly skilled task in musicians with dystonia.

Metabolic syndrome and mammographic density: The Study of Women’s Health Across the Nation (SWAN)

PubMed Central

Conroy, Shannon M.; Butler, Lesley M.; Harvey, Danielle; Gold, Ellen B.; Sternfeld, Barbara; Greendale, Gail A.; Habel, Laurel A.

2013-01-01

The metabolic syndrome (MetS) is associated with an increase in breast cancer risk. In this study, we evaluated whether the MetS was associated with an increase in percent mammographic density (MD), a breast cancer risk factor. We used linear regression and mixed models to examine the cross-sectional and longitudinal associations of the MetS and components of the MetS to percent MD in 790 pre- and early perimenopausal women enrolled in the Study of Women’s Health Across the Nation (SWAN). In cross-sectional analyses adjusted for body mass index (BMI), modest inverse associations were observed between percent MD and the MetS (β = −2.5, SE = 1.9, p = 0.19), abdominal adiposity (β = −4.8, SE = 1.9, p = 0.01) and raised glucose (β = −3.7, SE = 2.4, p = 0.12). In longitudinal models adjusted for covariates including age and BMI, abdominal adiposity (β = 0.34, SE = 0.17, p = 0.05) was significantly positively associated with slower annual decline in percent MD with time. In conclusion, our results do not support the hypothesis that the MetS increases breast cancer risk via a mechanism reflected by an increase in percent MD. PMID:21105041

Muscle dysmorphia: risk may be influenced by goals of the weightlifter.

PubMed

Skemp, Karen M; Mikat, Richard P; Schenck, Kyle P; Kramer, Natalie A

2013-09-01

Athletes with muscle dysmorphia suffer from constant dissatisfaction with body size and shape because they perceive themselves as smaller and less muscular than they actually are. There may be discrepancies among the various subgroups within the weightlifting community in regards to vulnerability and susceptibility to the development of MD. The purpose of this study, therefore, was to examine and compare MD symptomology between male and female, competitive and noncompetitive, and appearance-related and performance-related weightlifters. The MD assessments were made with the muscle dysmorphia inventory (MDI). The participants included 85 competitive (55 men and 30 women) and 48 noncompetitive (24 men and 24 women) weight training athletes. Each group included athletes with a primary focus on appearance enhancement or performance enhancement. Factorial analyses of variance were used to measure differences between each group on all MDI subscales. The results showed that men scored significantly higher than did women on the supplement (p = 0.006), physique protection (p = 0.039), and body size and symmetry subscales (p < 0.001). Competitive athletes scored significantly higher than noncompetitive athletes did on diet (p < 0.001), supplement (p < 0.001), exercise dependence (p < 0.001), and body size and symmetry (p = 0.002) subscales. Finally, the athletes focused on appearance enhancement scored significantly higher than athletes focused on performance enhancement on all 6 subscales (p < 0.01). Coaches and health and fitness professionals should understand that the goals of athletes in regard to weight training can influence susceptibility to development of MD symptoms. Knowing that athletes who engage in weight training to enhance appearance may exhibit greater behavioral characteristics than those athletes who do not may be helpful so they may be able to identify, prevent, and reverse MD in the athletes they serve.

Meta-Analysis of Creatine for Neuroprotection Against Parkinson's Disease.

PubMed

Attia; Ahmed, Hussien; Gadelkarim, Mohamed; Morsi, Mahmoud; Awad, Kamal; Elnenny, Mohamed; Ghanem, Esraa; El-Jaafary, Shaimaa; Negida, Ahmed

2017-01-01

Creatine is an antioxidant agent that showed neuroprotective effects in animal models of Parkinson's disease (PD). Creatine was selected by the National Institute of Neurological Disorders and Stroke as a possible disease modifying agent for Parkinson's disease. Therefore, many clinical trials evaluated the efficacy of creatine for patients with PD. The aim of this systematic review and meta-analysis is to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of Creatine for patients with PD. We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for PubMed, EBSCO, web of science and Ovid Midline was carried out. We included RCTs comparing creatine with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, and UPDRS III were pooled as mean difference (MD) between two groups from baseline to the endpoint. Statistical heterogeneity was assessed by visual inspection of the forest plot and measured by chi-square and I square tests. Three RCTs (n=1935) were included in this study. The overall effect did not favor either of the two groups in terms of: UPDRS total score (MD 1.07, 95% CI [3.38 to 1.25], UPDRS III (MD 0.62, 95% CI [2.27 to 1.02]), UPDRS II (MD 0.03, 95% CI [0.81 to 0.86], or UPDRS I (MD 0.03, 95% CI [0.33 to 0.28]). Current evidence does not support the use of creatine for neuroprotection against PD. Future well-designed, randomized controlled trials are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Perioperative Dextromethorphan as an Adjunct for Postoperative Pain: a Meta-Analysis of Randomized Controlled Trials

PubMed Central

King, Michael R.; Ladha, Karim S.; Gelineau, Amanda M.; Anderson, T. Anthony

2015-01-01

Background N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to reduce perioperative pain and opioid use. We performed a meta-analysis to determine whether the use of perioperative dextromethorphan lowers opioid consumption or pain scores. Methods PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, pubget, and Embase were searched. Studies were included if they were randomized, double-blinded, placebo controlled trials written in English, performed on patients ≥12 years. For comparison of opioid use, included studies tracked total consumption of intravenous or intramuscular opioids over 24 to 48 hours. Pain score comparisons were performed at 1 hour, 4 to 6 hours, and 24 hours postoperatively. Difference in means (MD) was used for effect size. Results Forty studies were identified and 21 were eligible for one or more comparisons. In 848 patients from 14 trials, opioid consumption favored dextromethorphan (MD -10.51 mg intravenous morphine equivalents; 95% confidence interval [CI]: -16.48 mg to -4.53 mg; p = 0.0006). In 884 patients from 13 trials, pain at 1 hour favored dextromethorphan (MD -1.60; 95% CI: -1.89 to -1.31; p < 0.00001). In 950 patients from 13 trials, pain at 4-6 hours favored dextromethorphan (MD -0.89; 95% CI: -1.11 to -0.66; p < 0.00001). In 797 patients from 12 trials, pain at 24 hours favored dextromethorphan (MD -0.92; 95% CI: -1.24 to -0.60; p < 0.00001). Conclusions This meta-analysis suggests dextromethorphan use perioperatively reduces postoperative opioid consumption at 24-48 hours and pain scores at 1, 4-6, and 24 hours. PMID:26587683

Perioperative Dextromethorphan as an Adjunct for Postoperative Pain: A Meta-analysis of Randomized Controlled Trials.

PubMed

King, Michael R; Ladha, Karim S; Gelineau, Amanda M; Anderson, T Anthony

2016-03-01

N-methyl-D-aspartate receptor antagonists have been shown to reduce perioperative pain and opioid use. The authors performed a meta-analysis to determine whether the use of perioperative dextromethorphan lowers opioid consumption or pain scores. PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Pubget, and EMBASE were searched. Studies were included if they were randomized, double-blinded, placebo-controlled trials written in English, and performed on patients 12 yr or older. For comparison of opioid use, included studies tracked total consumption of IV or intramuscular opioids over 24 to 48 h. Pain score comparisons were performed at 1, 4 to 6, and 24 h postoperatively. Difference in means (MD) was used for effect size. Forty studies were identified and 21 were eligible for one or more comparisons. In 848 patients from 14 trials, opioid consumption favored dextromethorphan (MD, -10.51 mg IV morphine equivalents; 95% CI, -16.48 to -4.53 mg; P = 0.0006). In 884 patients from 13 trials, pain at 1 h favored dextromethorphan (MD, -1.60; 95% CI, -1.89 to -1.31; P < 0.00001). In 950 patients from 13 trials, pain at 4 to 6 h favored dextromethorphan (MD, -0.89; 95% CI, -1.11 to -0.66; P < 0.00001). In 797 patients from 12 trials, pain at 24 h favored dextromethorphan (MD, -0.92; 95% CI, -1.24 to -0.60; P < 0.00001). This meta-analysis suggests that dextromethorphan use perioperatively reduces the postoperative opioid consumption at 24 to 48 h and pain scores at 1, 4 to 6, and 24 h.

The effectiveness of physical therapies for patients with base of thumb osteoarthritis: Systematic review and meta-analysis.

PubMed

Ahern, Malene; Skyllas, Jason; Wajon, Anne; Hush, Julia

2018-06-01

Trapeziometacarpal osteoarthritis (known as base of thumb OA) is a common condition causing pain and disability worldwide. The purpose of this review was to evaluate the effectiveness of multimodal and unimodal physical therapies for base of thumb osteoarthritis (OA) compared with usual care, placebo or sham interventions. Systematic review and meta-analysis. We searched MEDLINE (PubMed), CINAHL, Embase, AMED, PEDro, Cochrane Database of Systematic Review, Cochrane Register of Controlled Trials (CENTRAL) from inception to May 2017. Randomized controlled trials involving adults comparing physical therapy treatment for base of thumb OA with an inactive control (placebo or sham treatment) and reported pain, strength or functional outcomes were included. Meta-analyses were performed where possible. Methodological risk of bias was assessed with the Cochrane Risk of Bias tool. Five papers with low risk of bias were included. Meta-analyses of mean differences (MD) with 95% confidence intervals (95% CI), were calculated for between-group differences in point estimates at 4 weeks post-intervention. Multimodal and unimodal physical therapies resulted in clinically worthwhile improvements in pain intensity (MD 2.9 [95% CI 2.8 to 3.0]; MD 3.1 [95% CI 2.5 to 3.8] on a 0-10 scale, respectively). Hand function improved following unimodal treatments (MD 6.8 points [95% CI 1.7 to 11.9)] on a 0-100 scale) and after a multimodal treatment (MD 20.5 (95%CI -0.7 to 41.7). High quality evidence shows unimodal and multimodal physical therapy treatments can result in clinically worthwhile improvements in pain and function for patients with base of thumb OA. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Dosimetric comparing between protons beam and photons beam
for lung cancer radiotherapy: a meta-analysis].

PubMed

Tian, Guangwei; Li, Nan; Li, Guang

2013-05-01

The clinical evidences are not sufficient on the proton beam therapy of lung cancer for lacking of the RCTs on the comparing the proton with the photon beam in lung cancer radiotherapy. The aim of this study is to evaluate the dosimetry superiority of the proton beam and provide more valuable evidences to the clinical researches. Clinical trails of dosimetric comparing between protons beam and photons beam for lung cancer radiotherapy were obtained from the Cochrane library, Pubmed, EMbase, CBM, CNKI, VIP, and Wan Fang databases. The data included in the study were evaluated and analyzed using the Cochrane Collaboration's RevMan 5.2 software. Six trails were included. Compared to photon therapy (three-dimensional conformal photon radiotherapy, 3D-CRT), the proton therapy had a significantly lower total lung Dmean (MD=-4.15, 95%CI: -5.56--2.74, P<0.001) and V20, V10, V5 (MD=-10.92, 95%CI: -13.23--8.62, P<0.001); The V20, V10, V5 significantly decreased in proton therapy group. Compared to photon therapy (intensity-modulated photon radiotherapy, IMRT), V20, V10, V5 were also significantly lowered in proton therapy group (MD=-3.70, 95%CI: -5.31--2.10, P<0.001; MD=-8.86, 95%CI: -10.74--6.98, P<0.001; MD=-20.13, 95%CI: -27.11--13.14, P<0.001); The esophagus Dmean was not lowered, while the heart Dmean decreased in proton therapy group. Comparing to photon beam radiotherapy (3D-CRT and IMRT), proton beam therapy is advantageous in dosimetry of the lung cancer radiotherapy and recommended for clinical applying.

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study.

PubMed

Buckland, G; Ros, M M; Roswall, N; Bueno-de-Mesquita, H B; Travier, N; Tjonneland, A; Kiemeney, L A; Sacerdote, C; Tumino, R; Ljungberg, B; Gram, I T; Weiderpass, E; Skeie, G; Malm, J; Ehrnström, R; Chang-Claude, J; Mattiello, A; Agnoli, C; Peeters, P H; Boutron-Ruault, M C; Fagherazzi, G; Clavel-Chapelon, F; Nilsson, L M; Amiano, P; Trichopoulou, A; Oikonomou, E; Tsiotas, K; Sánchez, M J; Overvad, K; Quirós, J R; Chirlaque, M D; Barricarte, A; Key, T J; Allen, N E; Khaw, K T; Wareham, N; Riboli, E; Kaaks, R; Boeing, H; Palli, D; Romieu, I; Romaguera, D; Gonzalez, C A

2014-05-15

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. © 2013 UICC.

Zusanli (ST36) acupoint injection for preventing postoperative ileus: A systematic review and meta-analysis of randomized clinical trials.

PubMed

Wang, Mei; Gao, Yun-Hai; Xu, Jie; Chi, Yuan; Wei, Xiao-Bing; Lewith, George; Liu, Jian-Ping

2015-06-01

To evaluate the preventive effect of Zusanli (ST36) acupoint injections with various agents, for postoperative ileus (POI). We searched electronic databases for randomized controlled trials from inception to 1st February 2015 evaluating ST36 acupoint injection for preventing POI. Revman 5.2.0 was used for data analysis with effect estimates presented as mean difference (MD) with 95% confidence interval (CI). Statistical heterogeneity was tested using I(2) (defined as significant if I(2)>75%). We used a random effects model (REM) for pooling data with significant heterogeneity. Thirty trials involving 2967 participants were included. All trials were assessed as high risk of bias (poor methodological quality). For time to first flatus, meta-analysis favored ST36 acupoint injection of neostigmine (MD -20.70h, 95% CI -25.53 to -15.87, 15 trials, I(2)=98%, REM), vitamin B1 (MD -11.22h, 95% CI -17.01 to -5.43, 5 trials, I(2)=98%, REM), and metoclopramide (MD -15.65h, 95% CI -24.77 to -6.53, 3 trials, I(2)=94%, REM) compared to usual care alone. Meta-analysis of vitamin B1 favored ST36 acupoint injection compared to intra-muscular injection (MD -17.21h, 95% CI -21.05 to -13.36, 4 trials, I(2)=89%, REM). Similarly, for time to bowel sounds recovery and first defecation, ST36 acupoint injection also showed positive effects. ST36 acupoint injections with various agents may have a preventive effect for POI. Safety is inconclusive as few of included trials reported adverse events. Due to the poor methodological quality and likely publication bias further robust clinical trials are required to arrive at a definitive conclusion. Copyright © 2015 Elsevier Ltd. All rights reserved.

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Examining Perceptions about Mandatory Influenza Vaccination of Healthcare Workers through Online Comments on News Stories.

PubMed

Lei, Yang; Pereira, Jennifer A; Quach, Susan; Bettinger, Julie A; Kwong, Jeffrey C; Corace, Kimberly; Garber, Gary; Feinberg, Yael; Guay, Maryse

2015-01-01

The aim of this study was to understand online public perceptions of the debate surrounding the choice of annual influenza vaccinations or wearing masks as a condition of employment for healthcare workers, such as the one enacted in British Columbia in August 2012. Four national and 82 local (British Columbia) Canadian online news sites were searched for articles posted between August 2012 and May 2013 containing the words "healthcare workers" and "mandatory influenza vaccinations/immunizations" or "mandatory flu shots and healthcare workers." We included articles from sources that predominantly concerned our topic of interest and that generated reader comments. Two researchers coded the unedited comments using thematic analysis, categorizing codes to allow themes to emerge. In addition to themes, the comments were categorized by: 1) sentiment towards influenza vaccines; 2) support for mandatory vaccination policies; 3) citing of reference materials or statistics; 4) self-identified health-care worker status; and 5) sharing of a personal story. 1163 comments made by 648 commenters responding to 36 articles were analyzed. Popular themes included concerns about freedom of choice, vaccine effectiveness, patient safety, and distrust in government, public health, and the pharmaceutical industry. Almost half (48%) of commenters expressed a negative sentiment toward the influenza vaccine, 28% were positive, 20% were neutral, and 4% expressed mixed sentiment. Of those who commented on the policy, 75% did not support the condition to work policy, while 25% were in favour. Of the commenters, 11% self-identified as healthcare workers, 13% shared personal stories, and 18% cited a reference or statistic. The perception of the influenza vaccine in the comment sections of online news sites is fairly poor. Public health agencies should consider including online forums, comment sections, and social media sites as part of their communication channels to correct misinformation regarding the benefits of HCW influenza immunization and the effectiveness of the vaccine.

Examining Perceptions about Mandatory Influenza Vaccination of Healthcare Workers through Online Comments on News Stories

PubMed Central

Lei, Yang; Pereira, Jennifer A.; Quach, Susan; Bettinger, Julie A.; Kwong, Jeffrey C.; Corace, Kimberly; Garber, Gary; Feinberg, Yael; Guay, Maryse

2015-01-01

Background The aim of this study was to understand online public perceptions of the debate surrounding the choice of annual influenza vaccinations or wearing masks as a condition of employment for healthcare workers, such as the one enacted in British Columbia in August 2012. Methods Four national and 82 local (British Columbia) Canadian online news sites were searched for articles posted between August 2012 and May 2013 containing the words “healthcare workers” and “mandatory influenza vaccinations/immunizations” or “mandatory flu shots and healthcare workers.” We included articles from sources that predominantly concerned our topic of interest and that generated reader comments. Two researchers coded the unedited comments using thematic analysis, categorizing codes to allow themes to emerge. In addition to themes, the comments were categorized by: 1) sentiment towards influenza vaccines; 2) support for mandatory vaccination policies; 3) citing of reference materials or statistics; 4) self-identified health-care worker status; and 5) sharing of a personal story. Results 1163 comments made by 648 commenters responding to 36 articles were analyzed. Popular themes included concerns about freedom of choice, vaccine effectiveness, patient safety, and distrust in government, public health, and the pharmaceutical industry. Almost half (48%) of commenters expressed a negative sentiment toward the influenza vaccine, 28% were positive, 20% were neutral, and 4% expressed mixed sentiment. Of those who commented on the policy, 75% did not support the condition to work policy, while 25% were in favour. Of the commenters, 11% self-identified as healthcare workers, 13% shared personal stories, and 18% cited a reference or statistic. Interpretation The perception of the influenza vaccine in the comment sections of online news sites is fairly poor. Public health agencies should consider including online forums, comment sections, and social media sites as part of their communication channels to correct misinformation regarding the benefits of HCW influenza immunization and the effectiveness of the vaccine. PMID:26086194

What will it take? Pathways, time and funding: Australian medical students' perspective on clinician-scientist training.

PubMed

Eley, Diann S; Jensen, Charmaine; Thomas, Ranjeny; Benham, Helen

2017-12-08

Clinician-scientists are in decline worldwide. They represent a unique niche in medicine by bridging the gap between scientific discovery and patient care. A national, integrated approach to training clinician-scientists, typically programs that comprise a comprehensive MD-PhD pathway, are customary. Such a pathway is lacking in Australia. The objective was to gather perceptions from Australian medical students on factors they perceive would influence their decision to pursue clinician-scientist training. A cross-sectional mixed methods design used quantitative and qualitative questions in an online self-report survey with medical students from a four-year MD program. Quantitative measures comprised scaled response questions regarding prior experience and current involvement in research, and short- and long-term opinions about factors that influence their decisions to undertake a research higher degree (RHD) during medical school. Qualitative questions gathered broader perceptions of what a career pathway as a clinician-scientist would include and what factors are most conducive to a medical student's commitment to MD-PhD training. Respondents (N = 418; 51% female) indicated Time, Funding and Pathway as the major themes arising from the qualitative data, highlighting negative perceptions rather than possible benefits to RHD training. The lack of an evident Pathway was inter-related to Time and Funding. Themes were supported by the quantitative data. Sixty percent of students have previous research experience of varying forms, and 90% report a current interest, mainly to improve their career prospects. The data emphasise the need for an MD-PhD pathway in Australia. A model that provides an early, integrated, and exclusive approach to research training pathways across all stages of medical education is suggested as the best way to rejuvenate the clinician-scientist. A national pathway that addresses factors influencing career decision making throughout the medical education continuum should include an appropriate funding structure, and provide early and continuing advice and mentoring. It should be flexible, gender equitable, and include post-graduate training. The implications of implementing MD-PhD programs represent a substantial investment. However this should not be a deterrent to Australia's commitment to an MD-PhD pathway, but rather a challenge to help ensure our future healthcare is guided by highly trained and competent clinician-scientists.

Commentary: Dr John Brownlee MA, MD, DSc, DPH (Cantab), FRFPS, FSS, FRMetS (1868-1927), public health officer, geneticist, epidemiologist and medical statistician.

PubMed

Farewell, Vern T; Johnson, Tony L

2013-08-01

In July 1914 Dr John Brownlee was appointed head of the Statistical Department of the newly established Medical Research Committee. He had qualified in mathematics, natural philosophy and medicine at the University of Glasgow, and by 1914 had established a reputation as a public health officer, an expert in infectious diseases, and as a proponent of the Pearsonian school of the application of statistics and mathematics to medicine: an ideal background for his new position. In celebration of the centenary anniversary of the Medical Research Council and as a tribute to John Brownlee's involvement at the start, the International Journal of Epidemiology is reprinting in this issue one of his early papers on genetics. We comment on this paper, as well as Brownlee's background, achievements, research and his somewhat enigmatic though likeable character.

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...Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the National Institute of General Medical Sciences (NIGMS), the National Institutes of Health (NIH) has submitted to the Office of Management and Budget (OMB) a request to review and approve the information collection listed below. This proposed information collection was previously published in the Federal Register on May 18, 2010, pages 27789-27790, and allowed 60 days for public comment. One comment was received on 6/25/2010. The public respondent requested that eligibility for this program be offered to American citizens only. As stated in A.1., Justification, of the Supporting Statement A, applicants for this program must be U.S. citizens or permanent residents of the United States who have been awarded a terminal degree, or who have been certified by a university as meeting all the requirements leading to a doctorate may be hired as PRAT Fellows. The purpose of this notice is to allow an additional 30 days for public comment. The National Institutes of Health may not conduct or sponsor, and the respondent is not required to respond to, an information collection that has been extended, revised, or implemented on or after October 1, 1995, unless it displays a currently valid OMB control number. Proposed Collection: Title: Application for the Pharmacology Research Associate Program. Type of Information Collection Request: Extension of a currently approved collection. Need and Use of Information Collection: The Pharmacology Research Associate (PRAT) Program will use the applicant and referee information to award opportunities for training and experience in laboratory or clinical investigation to individuals with a Ph.D. degree in pharmacology or a related science, M.D., or other professional degree through appointments as PRAT Fellows at the National Institutes of Health or the Food and Drug Administration. The goal of the program is to develop leaders in pharmacological research for key positions in academic, industrial, and Federal research laboratories. Frequency of Response: Once a year. Affected Public: Individuals or households; Businesses or other for-profit. Type of Respondents: Applicants and Referees. The annual reporting burden is as follows:

The neurophysiological features of myoclonus-dystonia and differentiation from other dystonias.

PubMed

Popa, Traian; Milani, Paolo; Richard, Aliénor; Hubsch, Cécile; Brochard, Vanessa; Tranchant, Christine; Sadnicka, Anna; Rothwell, John; Vidailhet, Marie; Meunier, Sabine; Roze, Emmanuel

2014-05-01

Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown. To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias. We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale. Myoclonus-dystonia with a proven SGCE mutation. We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores. We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other forms of primary dystonia. Myoclonus-dystonia patients also shared some common pathophysiological features of dystonia, including enhanced responsiveness of the motor cortex to plasticity induction and abnormal response to cerebellar conditioning as tested by EBCC. Specific underlying dysfunctions are associated with the very particular clinical phenotype of M-D and make it a unique entity that stands apart from other primary dystonias.

Apple RING E3 ligase MdMIEL1 inhibits anthocyanin accumulation by ubiquitinating and degrading MdMYB1 protein.

PubMed

An, Jian-Ping; Liu, Xin; Li, Hao-Hao; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-11-01

MdMYB1 is an important regulator for anthocyanin accumulation in apple (Malus × domestica). Here, an apple RING E3 ligase, MdMIEL1, was screened out as a partner of MdMYB1 with a yeast two-hybrid approach. Pull-down, bimolecular fluorescence complementation and coimmunoprecipitation assays further verified the interaction between MdMIEL1 and MdMYB1 proteins. Subsequently, in vitro and in vivo experiments indicated that MdMIEL1 functioned as a ubiquitin E3 ligase to ubiquitinate MdMYB1 protein, followed by degradation through a 26S proteasome pathway. Furthermore, transgenic studies in apple calli and Arabidopsis demonstrated that MdMIEL1 negatively regulated anthocyanin accumulation by modulating the degradation of MdMYB1 protein. Taken together, our findings provide a new insight into the molecular mechanism by which MdMIEL1 negatively regulates anthocyanin biosynthesis by ubiquitinating and degrading MdMYB1 protein. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Analytical and molecular dynamics studies on the impact loading of single-layered graphene sheet by fullerene

NASA Astrophysics Data System (ADS)

Hosseini-Hashemi, Shahrokh; Sepahi-Boroujeni, Amin; Sepahi-Boroujeni, Saeid

2018-04-01

Normal impact performance of a system including a fullerene molecule and a single-layered graphene sheet is studied in the present paper. Firstly, through a mathematical approach, a new contact law is derived to describe the overall non-bonding interaction forces of the "hollow indenter-target" system. Preliminary verifications show that the derived contact law gives a reliable picture of force field of the system which is in good agreements with the results of molecular dynamics (MD) simulations. Afterwards, equation of the transversal motion of graphene sheet is utilized on the basis of both the nonlocal theory of elasticity and the assumptions of classical plate theory. Then, to derive dynamic behavior of the system, a set including the proposed contact law and the equations of motion of both graphene sheet and fullerene molecule is solved numerically. In order to evaluate outcomes of this method, the problem is modeled by MD simulation. Despite intrinsic differences between analytical and MD methods as well as various errors arise due to transient nature of the problem, acceptable agreements are established between analytical and MD outcomes. As a result, the proposed analytical method can be reliably used to address similar impact problems. Furthermore, it is found that a single-layered graphene sheet is capable of trapping fullerenes approaching with low velocities. Otherwise, in case of rebound, the sheet effectively absorbs predominant portion of fullerene energy.

Blood pressure lowering efficacy of renin inhibitors for primary hypertension.

PubMed

Musini, Vijaya M; Lawrence, Kendra Ak; Fortin, Patricia M; Bassett, Ken; Wright, James M

2017-04-05

Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension.To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available.Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias.Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes.Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

Osmotic and stimulant laxatives for the management of childhood constipation.

PubMed

Gordon, Morris; MacDonald, John K; Parker, Claire E; Akobeng, Anthony K; Thomas, Adrian G

2016-08-17

Constipation within childhood is an extremely common problem. Despite the widespread use of osmotic and stimulant laxatives by health professionals to manage constipation in children, there has been a long standing paucity of high quality evidence to support this practice. We set out to evaluate the efficacy and safety of osmotic and stimulant laxatives used to treat functional childhood constipation. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialized Trials Register from inception to 10 March 2016. There were no language restrictions. We also searched the references of all included studies, personal contacts and drug companies to identify studies. Randomised controlled trials (RCTs) which compared osmotic or stimulant laxatives to placebo or another intervention, with participants aged 0 to 18 years old were considered for inclusion. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. Relevant papers were identified and two authors independently assessed the eligibility of trials, extracted data and assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was frequency of defecation. Secondary endpoints included faecal incontinence, disimpaction, need for additional therapies and adverse events. For continuous outcomes we calculated the mean difference (MD) and 95% confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we calculated the risk ratio (RR) and 95% CI using a fixed-effect model. The Chi(2) and I(2) statistics were used to assess statistical heterogeneity. A random-effects model was used in situations of unexplained heterogeneity. We assessed the overall quality of the evidence supporting the primary and secondary outcomes using the GRADE criteria. Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed guar gum and lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95). The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil). There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin. The optimal dose of PEG also warrants further investigation.

24 CFR 570.704 - Application requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... examine the application's contents and to provide comments on the proposed application. (iv) Prepare its... must consider any such comments and views received and, if the public entity deems appropriate, modify... comment on, proposed activities not previously included in an application and activities which are...

McArdle Disease and Exercise Physiology.

PubMed

Kitaoka, Yu

2014-02-25

McArdle disease (glycogen storage disease Type V; MD) is a metabolic myopathy caused by a deficiency in muscle glycogen phosphorylase. Since muscle glycogen is an important fuel for muscle during exercise, this inborn error of metabolism provides a model for understanding the role of glycogen in muscle function and the compensatory adaptations that occur in response to impaired glycogenolysis. Patients with MD have exercise intolerance with symptoms including premature fatigue, myalgia, and/or muscle cramps. Despite this, MD patients are able to perform prolonged exercise as a result of the "second wind" phenomenon, owing to the improved delivery of extra-muscular fuels during exercise. The present review will cover what this disease can teach us about exercise physiology, and particularly focuses on the compensatory pathways for energy delivery to muscle in the absence of glycogenolysis.

MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

PubMed

Hu, Da-Gang; Sun, Cui-Hui; Sun, Mei-Hong; Hao, Yu-Jin

2016-03-01

Salt-induced phosphorylation of MdVHA-B1 protein was mediated by MdSOS2L1 protein kinase, and thereby increasing malate content in apple. Salinity is an important environmental factor that influences malate accumulation in apple. However, the molecular mechanism by which salinity regulates this process is poorly understood. In this work, we found that MdSOS2L1, a novel AtSOS2-LIKE protein kinase, interacts with V-ATPase subunit MdVHA-B1. Furthermore, MdSOS2L1 directly phosphorylates MdVHA-B1 at Ser(396) site to modulate malate accumulation in response to salt stress. Meanwhile, a series of transgenic analyses in apple calli showed that the MdSOS2L1-MdVHAB1 pathway was involved in the regulation of malate accumulation. Finally, a viral vector-based transformation approach demonstrated that the MdSOS2L1-MdVHAB1 pathway also modulated malate accumulation in apple fruits with or without salt stress. Collectively, our findings provide a new insight into the mechanism by which MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

Identification of SFBB-containing canonical and noncanonical SCF complexes in pollen of apple (Malus × domestica).

PubMed

Minamikawa, Mai F; Koyano, Ruriko; Kikuchi, Shinji; Koba, Takato; Sassa, Hidenori

2014-01-01

Gametophytic self-incompatibility (GSI) of Rosaceae, Solanaceae and Plantaginaceae is controlled by a single polymorphic S locus. The S locus contains at least two genes, S-RNase and F-box protein encoding gene SLF/SFB/SFBB that control pistil and pollen specificity, respectively. Generally, the F-box protein forms an E3 ligase complex, SCF complex with Skp1, Cullin1 (CUL1) and Rbx1, however, in Petunia inflata, SBP1 (S-RNase binding protein1) was reported to play the role of Skp1 and Rbx1, and form an SCFSLF-like complex for ubiquitination of non-self S-RNases. On the other hand, in Petunia hybrida and Petunia inflata of Solanaceae, Prunus avium and Pyrus bretschneideri of Rosaceae, SSK1 (SLF-interacting Skp1-like protein1) is considered to form the SCFSLF/SFB complex. Here, we isolated pollen-expressed apple homologs of SSK1 and CUL1, and named MdSSK1, MdCUL1A and MdCUL1B. MdSSK1 was preferentially expressed in pollen, but weakly in other organs analyzed, while, MdCUL1A and MdCUL1B were almost equally expressed in all the organs analyzed. MdSSK1 transcript abundance was significantly (>100 times) higher than that of MdSBP1. In vitro binding assays showed that MdSSK1 and MdSBP1 interacted with MdSFBB1-S9 and MdCUL1, and MdSFBB1-S9 interacted more strongly with MdSSK1 than with MdSBP1. The results suggest that both MdSSK1-containing SCFSFBB1 and MdSBP1-containing SCFSFBB1-like complexes function in pollen of apple, and the former plays a major role.

The Therapeutic Effects of a Traditional Chinese Medicine Formula Wuzi Yanzong Pill for the Treatment of Oligoasthenozoospermia: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Xiao; Kong, Grace Wing Shan; Wu, Justin Che Yuen; Li, Tin Chiu

2018-01-01

Oligoasthenozoospermia is a crucial factor in male infertility. Wuzi Yanzong (WZYZ) pill is a popular traditional Chinese medicine (TCM) formula which has been used for male infertility treatment for years. However, its effects on semen quality remain controversial. We conducted a preregistered meta-analysis to assess the effect of WZYZ pill for the therapeutic effects on oligoasthenozoospermia. Five randomized controlled trials including 960 participants were selected from databases of domains in North-East Asian regions, PubMed, Embase, and Cochrane Library. WZYZ pill group yielded a greater mean increment on sperm concentration (5 trials: MD 5.99, 95% CI 2.12–9.85, P = 0.002), sperm motility (5 trials: MD 4.57, 95% CI 0.47–8.68, P = 0.03), sperm morphology (2 trials: MD −1.93, 95% CI −4.87–1.01, P = 0.20), activity of acrosomal enzyme (2 trials: MD 28.27, 95% CI 12.41–44.14, P < 0.01), volume of semen (2 trials: MD 0.56, 95% CI 0.21–0.91, P = 0.002), and a decrement of sperm DNA fragmentation index (2 trials: MD −3.82, 95% CI −6.45–−1.19, P = 0.004). However, qualities of selected studies were generally unsatisfactory, and there was inherent heterogeneity among some of the outcomes. Despite these limitations, the WZYZ pill improved sperm quality by improving several semen parameters and decreasing DNA damage in oligoasthenozoospermia patients. PMID:29576794

Genome-wide identification and characterization of the apple (Malus domestica) HECT ubiquitin-protein ligase family and expression analysis of their responsiveness to abiotic stresses.

PubMed

Xu, Jianing; Xing, Shanshan; Cui, Haoran; Chen, Xuesen; Wang, Xiaoyun

2016-04-01

The ubiquitin-protein ligases (E3s) directly participate in ubiquitin (Ub) transferring to the target proteins in the ubiquitination pathway. The HECT ubiquitin-protein ligase (UPL), one type of E3s, is characterized as containing a conserved HECT domain of approximately 350 amino acids in the C terminus. Some UPLs were found to be involved in trichome development and leaf senescence in Arabidopsis. However, studies on plant UPLs, such as characteristics of the protein structure, predicted functional motifs of the HECT domain, and the regulatory expression of UPLs have all been limited. Here, we present genome-wide identification of the genes encoding UPLs (HECT gene) in apple. The 13 genes (named as MdUPL1-MdUPL13) from ten different chromosomes were divided into four groups by phylogenetic analysis. Among these groups, the encoding genes in the intron-exon structure and the included additional functional domains were quite different. Notably, the F-box domain was first found in MdUPL7 in plant UPLs. The HECT domain in different MdUPL groups also presented different spatial features and three types of conservative motifs were identified. The promoters of each MdUPL member carried multiple stress-response related elements by cis-acting element analysis. Experimental results demonstrated that the expressions of several MdUPLs were quite sensitive to cold-, drought-, and salt-stresses by qRT-PCR assay. The results of this study helped to elucidate the functions of HECT proteins, especially in Rosaceae plants.

Adherence to Mediterranean diet in relation to bone mineral density and risk of fracture: a systematic review and meta-analysis of observational studies.

PubMed

Malmir, Hanieh; Saneei, Parvane; Larijani, Bagher; Esmaillzadeh, Ahmad

2017-06-21

We aimed to systematically review available data on the association between adherence to MD and BMD as well as risk of fractures and to summarize this information through a meta-analysis. Previous studies in the field of adherence to MD in relation to BMD and risk of fracture were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases prior to June, 2016 using Mesh and non-Mesh relevant keywords. In the meta-analysis of four effect sizes, obtained from three studies, we found that adherence to MD was associated with a 21% reduced risk of hip fracture (overall RR 0.79; 95% CIs 0.72-0.87). Adherence to MD was positively associated with lumber spine ' s (mean difference of BMD comparing highest and lowest categories of MD score 0.12; 95% CI 0.06-0.19 g/cm 2 ), femoral neck (0.10; 0.06-0.15 g/cm 2 ) and total hip (0.11; 0.09-0.14 g/cm 2 ) BMD. Meta-regression of included observational studies revealed a significant inverse linear association between Mediterranean diet score and risk of hip fracture, such that one unit increase in the score of Mediterranean diet was associated with a reduction in the risk of hip fracture (RR 0.95, 95% CI 0.92-0.98 p = 0.01). Adherence to MD was associated with a reduced risk of fracture as well as with a higher mean BMD.

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy

PubMed Central

Saulle, Rosella; Di Murro, Francesca; Siliquini, Roberta; Firenze, Alberto; Maurici, Massimo; Mannocci, Alice; Colamesta, Vittoria; Barillà, Francesco; Ferrante, Fabio; Agati, Luciano

2018-01-01

Background Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Design Case-control study. Methods Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. Results 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. Conclusion Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits. PMID:29543823

DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression

PubMed Central

Zill, Peter; Baghai, Thomas C.; Schüle, Cornelius; Born, Christoph; Früstück, Clemens; Büttner, Andreas; Eisenmenger, Wolfgang; Varallo-Bedarida, Gabriella; Rupprecht, Rainer; Möller, Hans-Jürgen; Bondy, Brigitta

2012-01-01

Background The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ∼40%–50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. Materials and Methods The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. Results We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). Conclusion The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders. PMID:22808171

Length scale effects of friction in particle compaction using atomistic simulations and a friction scaling model

NASA Astrophysics Data System (ADS)

Stone, T. W.; Horstemeyer, M. F.

2012-09-01

The objective of this study is to illustrate and quantify the length scale effects related to interparticle friction under compaction. Previous studies have shown as the length scale of a specimen decreases, the strength of a single crystal metal or ceramic increases. The question underlying this research effort continues the thought—If there is a length scale parameter related to the strength of a material, is there a length scale parameter related to friction? To explore the length scale effects of friction, molecular dynamics (MD) simulations using an embedded atom method potential were performed to analyze the compression of two spherical FCC nickel nanoparticles at different contact angles. In the MD model study, we applied a macroscopic plastic contact formulation to determine the normal plastic contact force at the particle interfaces and used the average shear stress from the MD simulations to determine the tangential contact forces. Combining this information with the Coulomb friction law, we quantified the MD interparticle coefficient of friction and showed good agreement with experimental studies and a Discrete Element Method prediction as a function of contact angle. Lastly, we compared our MD simulation friction values to the tribological predictions of Bhushan and Nosonovsky (BN), who developed a friction scaling model based on strain gradient plasticity and dislocation-assisted sliding that included a length scale parameter. The comparison revealed that the BN elastic friction scaling model did a much better job than the BN plastic scaling model of predicting the coefficient of friction values obtained from the MD simulations.

Meta-analysis of optical low-coherence reflectometry versus partial coherence interferometry biometry.

PubMed

Huang, Jinhai; McAlinden, Colm; Huang, Yingying; Wen, Daizong; Savini, Giacomo; Tu, Ruixue; Wang, Qinmei

2017-02-24

A meta-analysis to compare ocular biometry measured by optical low-coherence reflectometry (Lenstar LS900; Haag Streit) and partial coherence interferometry (the IOLMaster optical biometer; Carl Zeiss Meditec). A systematic literature search was conducted for articles published up to August 6th 2015 in the Cochrane Library, PubMed, Medline, Embase, China Knowledge Resource Integrated Database and Wanfang Data. A total of 18 studies involving 1921 eyes were included. There were no statistically significant differences in axial length (mean difference [MD] 0 mm; 95% confidence interval (CI) -0.08 to 0.08 mm; p = 0.92), anterior chamber depth (MD 0.02 mm; 95% CI -0.07 to 0.10 mm; p = 0.67), flat keratometry (MD -0.05 D; 95% CI -0.16 to 0.06 D; p = 0.39), steep keratometry (MD -0.09 D; 95% CI -0.20 to 0.03 D; p = 0.13), and mean keratometry (MD -0.15 D; 95% CI -0.30 to 0.00 D; p = 0.05). The white to white distance showed a statistically significant difference (MD -0.14 mm; 95% CI -0.25 to -0.02 mm; p = 0.02). In conclusion, there was no difference in the comparison of AL, ACD and keratometry readings between the Lenstar and IOLMaster. However the WTW distance indicated a statistically significant difference between the two devices. Apart from the WTW distance, measurements for AL, ACD and keratometry readings may be used interchangeability with both devices.

43 CFR 10010.37 - Inviting comments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... may be requested from local agencies through these procedures to the extent that they include the affected local jurisdictions. (b) When the proposed action may affect the environment of an Indian... POLICY ACT Environmental Impact Statements § 10010.37 Inviting comments. (a) Comments from State agencies...

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Long Range Transport of War-Related Burn Casualties

DTIC Science & Technology

2008-02-01

Long Range Transport of War-Related Burn Casualties Evan M. Renz, MD, FACS, Leopoldo C . Cancio, MD, FACS, David J. Barillo, MD, FACS, Christopher E...White, MD, FACS, Michael C . Albrecht, MD, Charles K. Thompson, PA- C , Jody L. Ennis, RN, BSN, Sandra M. Wanek, MD, James A. King, MD, FACEP, Kevin K...sched- Submitted for publication October 29, 2007. Accepted for publication October 30, 2007. Copyright © 2008 by Lippincott Williams & Wilkins From the

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Molecular dynamics studies of electron-ion temperature equilibration in hydrogen plasmas within the coupled-mode regime

DOE PAGES

Benedict, Lorin X.; Surh, Michael P.; Stanton, Liam G.; ...

2017-04-10

Here, we use classical molecular dynamics (MD) to study electron-ion temperature equilibration in two-component plasmas in regimes for which the presence of coupled collective modes has been predicted to substantively reduce the equilibration rate. Guided by previous kinetic theory work, we examine hydrogen plasmas at a density of n = 10 26cm –3, T i = 10 5K, and 10 7 K < Te < 10 9K. The nonequilibrium classical MD simulations are performed with interparticle interactions modeled by quantum statistical potentials (QSPs). Our MD results indicate (i) a large effect from time-varying potential energy, which we quantify by appealingmore » to an adiabatic two-temperature equation of state, and (ii) a notable deviation in the energy equilibration rate when compared to calculations from classical Lenard-Balescu theory including the QSPs. In particular, it is shown that the energy equilibration rates from MD are more similar to those of the theory when coupled modes are neglected. We suggest possible reasons for this surprising result and propose directions of further research along these lines.« less

Primary Hyperparathyroidism and Hyperthyroidism in a Patient with Myotonic Dystrophy: A Case Report and Review of the Literature

PubMed Central

Alaya, Wafa; Berriche, Olfa; Younes, Samia; Sfar, Mohamed Habib

2015-01-01

Various endocrine manifestations are commonly described in myotonic dystrophy (MD), including primary hypogonadism, diabetes mellitus, and thyroid and parathyroid dysfunction. We describe a 46-year-old woman with a family history of MD with her son. She was diagnosed with cardiac arrhythmia and required the implantation of a pacemaker. She was noted to have a bilateral cataract. She complained of muscle weakness, diffuse myalgia, and palpitation. The electromyography (EMG) showed myotonic discharges. Laboratory tests showed high serum calcium 2.83 mmol/L, serum phosphate 1.2 mmol/L, parathormone 362.5 pg/mL, thyroid stimulating hormone TSH 0.02 mIU/L (normal range: 0.34–5.6 mIU/L), FT4 21.17 ng/mL, and negative anti-thyroperoxidase antibodies. Cervical ultrasound revealed a multinodular goiter. The 99mTc-MIBI scintigraphy localized a lower right parathyroid adenoma. The clinical data, the family history of MD, EMG data, and endocrine disturbances were strongly suggestive of MD associated with hyperthyroidism and primary hyperparathyroidism. PMID:26175917

The NASA master directory: Quick reference guide

NASA Technical Reports Server (NTRS)

Satin, Karen (Editor); Kanga, Carol (Editor)

1989-01-01

This is a quick reference guide to the NASA Master Directory (MD), which is a free, online, multidisciplinary directory of space and Earth science data sets (NASA and non-NASA data) that are of potential interest to the NASA-sponsored research community. The MD contains high-level descriptions of data sets, other data systems and archives, and campaigns and projects. It provides mechanisms for searching for data sets by important criteria such as geophysical parameters, time, and spatial coverage, and provides information on ordering the data. It also provides automatic connections to a number of data systems such as the NASA Climate Data System, the Planetary Data System, the NASA Ocean Data System, the Pilot Land Data System, and others. The MD includes general information about many data systems, data centers, and coordinated data analysis projects, It represents the first major step in the Catalog Interoperability project, whose objective is to enable researchers to quickly and efficiently identify, obtain information about, and get access to space and Earth science data. The guide describes how to access, use, and exit the MD and lists its features.

Integrated experimental and theoretical approach for the structural characterization of Hg2+ aqueous solutions

NASA Astrophysics Data System (ADS)

D'Angelo, Paola; Migliorati, Valentina; Mancini, Giordano; Barone, Vincenzo; Chillemi, Giovanni

2008-02-01

The structural and dynamic properties of the solvated Hg2+ ion in aqueous solution have been investigated by a combined experimental-theoretical approach employing x-ray absorption spectroscopy and molecular dynamics (MD) simulations. This method allows one to perform a quantitative analysis of the x-ray absorption near-edge structure (XANES) spectra of ionic solutions using a proper description of the thermal and structural fluctuations. XANES spectra have been computed starting from the MD trajectory, without carrying out any minimization in the structural parameter space. The XANES experimental data are accurately reproduced by a first-shell heptacoordinated cluster only if the second hydration shell is included in the calculations. These results confirm at the same time the existence of a sevenfold first hydration shell for the Hg2+ ion in aqueous solution and the reliability of the potentials used in the MD simulations. The combination of MD and XANES is found to be very helpful to get important new insights into the quantitative estimation of structural properties of disordered systems.

Anharmonic Infrared Spectroscopy through the Fourier Transform of Time Correlation Function Formalism in ONETEP.

PubMed

Vitale, Valerio; Dziedzic, Jacek; Dubois, Simon M-M; Fangohr, Hans; Skylaris, Chris-Kriton

2015-07-14

Density functional theory molecular dynamics (DFT-MD) provides an efficient framework for accurately computing several types of spectra. The major benefit of DFT-MD approaches lies in the ability to naturally take into account the effects of temperature and anharmonicity, without having to introduce any ad hoc or a posteriori corrections. Consequently, computational spectroscopy based on DFT-MD approaches plays a pivotal role in the understanding and assignment of experimental peaks and bands at finite temperature, particularly in the case of floppy molecules. Linear-scaling DFT methods can be used to study large and complex systems, such as peptides, DNA strands, amorphous solids, and molecules in solution. Here, we present the implementation of DFT-MD IR spectroscopy in the ONETEP linear-scaling code. In addition, two methods for partitioning the dipole moment within the ONETEP framework are presented. Dipole moment partitioning allows us to compute spectra of molecules in solution, which fully include the effects of the solvent, while at the same time removing the solvent contribution from the spectra.

MDTRA: a molecular dynamics trajectory analyzer with a graphical user interface.

PubMed

Popov, Alexander V; Vorobjev, Yury N; Zharkov, Dmitry O

2013-02-05

Most of existing software for analysis of molecular dynamics (MD) simulation results is based on command-line, script-guided processes that require the researchers to have an idea about programming language constructions used, often applied to the one and only product. Here, we describe an open-source cross-platform program, MD Trajectory Reader and Analyzer (MDTRA), that performs a large number of MD analysis tasks assisted with a graphical user interface. The program has been developed to facilitate the process of search and visualization of results. MDTRA can handle trajectories as sets of protein data bank files and presents tools and guidelines to convert some other trajectory formats into such sets. The parameters analyzed by MDTRA include interatomic distances, angles, dihedral angles, angles between planes, one-dimensional and two-dimensional root-mean-square deviation, solvent-accessible area, and so on. As an example of using the program, we describe the application of MDTRA to analyze the MD of formamidopyrimidine-DNA glycosylase, a DNA repair enzyme from Escherichia coli. Copyright © 2012 Wiley Periodicals, Inc.

Metadynamics Enhanced Markov Modeling of Protein Dynamics.

PubMed

Biswas, Mithun; Lickert, Benjamin; Stock, Gerhard

2018-05-31

Enhanced sampling techniques represent a versatile approach to account for rare conformational transitions in biomolecules. A particularly promising strategy is to combine massive parallel computing of short molecular dynamics (MD) trajectories (to sample the free energy landscape of the system) with Markov state modeling (to rebuild the kinetics from the sampled data). To obtain well-distributed initial structures for the short trajectories, it is proposed to employ metadynamics MD, which quickly sweeps through the entire free energy landscape of interest. Being only used to generate initial conformations, the implementation of metadynamics can be simple and fast. The conformational dynamics of helical peptide Aib 9 is adopted to discuss various technical issues of the approach, including metadynamics settings, minimal number and length of short MD trajectories, and the validation of the resulting Markov models. Using metadynamics to launch some thousands of nanosecond trajectories, several Markov state models are constructed that reveal that previous unbiased MD simulations of in total 16 μs length cannot provide correct equilibrium populations or qualitative features of the pathway distribution of the short peptide.

Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009 (Morbidity and Mortality Weekly Report. Volume 59, Number RR-6, July 23, 2010)

DTIC Science & Technology

2010-07-23

western states, including California, Montana, Nevada, and New Mexico (45). Cases that occur sporadically in both domestic livestock and free-ranging...eczema, and herpes simplex or varicella zoster. In addition, depending on the epidemiologic history or route of exposure, parapoxvirus infection (orf...Beck, JD, Consumer Representative, Palmyra, Virginia; Lance Chilton, MD, University of New Mexico , Albuquerque, New Mexico ; Paul Cieslak, MD, Oregon

Geothermal Thermoelectric Generation (G-TEG) with Integrated Temperature Driven Membrane Distillation and Novel Manganese Oxide for Lithium Extraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renew, Jay; Hansen, Tim

Southern Research Institute (Southern) teamed with partners Novus Energy Technologies (Novus), Carus Corporation (Carus), and Applied Membrane Technology, Inc. (AMT) to develop an innovative Geothermal ThermoElectric Generation (G-TEG) system specially designed to both generate electricity and extract high-value lithium (Li) from low-temperature geothermal brines. The process combined five modular technologies including – silica removal, nanofiltration (NF), membrane distillation (MD), Mn-oxide sorbent for Li recovery, and TEG. This project provides a proof of concept for each of these technologies. The first step in the process is silica precipitation through metal addition and pH adjustment to prevent downstream scaling in membrane processes.more » Next, the geothermal brine is concentrated with the first of a two stage MD system. The first stage MD system is made of a high-temperature material to withstand geothermal brine temperatures up to 150C.° The first stage MD is integrated with a G-TEG module for simultaneous energy generation. The release of energy from the MD permeate drives heat transfer across the TE module, producing electricity. The first stage MD concentrate is then treated utilizing an NF system to remove Ca 2+ and Mg 2+. The NF concentrate will be disposed in the well by reinjection. The NF permeate undergoes concentration in a second stage of MD (polymeric material) to further concentrate Li in the NF permeate and enhance the efficiency of the downstream Li recovery process utilizing a Mn-oxide sorbent. Permeate from both the stages of the MD can be beneficially utilized as the permeates will contain less contaminants than the feed water. The concentrated geothermal brines are then contacted with the Mn-oxide sorbent. After Li from the geothermal brine is adsorbed on the sorbent, HCl is then utilized to regenerate the sorbent and recover the Li. The research and development project showed that the Si removal goal (>80%) could be achieved by increasing the pH of the brine and adding Fe 3+ under several scenarios. The NF was also successful in achieving significant Ca 2+ and Mg 2+ removal (~80%) while retaining most Li in the permeate for high strength brines. MD experiments showed that geothermal brines could be significantly concentrated with little fouling due to pre-treatment.« less

Efficacy and Safety of Tai Chi for Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Ni, Xiaojia; Liu, Shaonan; Lu, Fuchang; Shi, Xiaogeng; Guo, Xinfeng

2014-01-01

Background and Objective In Parkinson's disease (PD), wearing off and side effects of long-term medication and complications pose challenges for neurologists. Although Tai Chi is beneficial for many illnesses, its efficacy for PD remains uncertain. The purpose of this review was to evaluate the efficacy and safety of Tai Chi for PD. Methods Randomized controlled trials (RCTs) of Tai Chi for PD were electronically searched by the end of December 2013 and identified by two independent reviewers. The tool from the Cochrane Handbook 5.1 was used to assess the risk of bias. A standard meta-analysis was performed using RevMan 5.2 software. Results Ten trials with PD of mild-to-moderate severity were included in the review, and nine trials (n = 409) were included in the meta-analysis. The risk of bias was generally high in the blinding of participants and personnel. Improvements in the Unified Parkinson's Disease Rating Scale Part III (mean difference (MD) −4.34, 95% confidence interval (CI) −6.67–−2.01), Berg Balance Scale (MD: 4.25, 95% CI: 2.83–5.66), functional reach test (MD: 3.89, 95% CI: 1.73–6.04), Timed Up and Go test (MD: −0.75, 95% CI: −1.30–−0.21), stride length (standardized MD: 0.56, 95% CI: 0.03–1.09), health-related quality of life (standardized MD: −1.10, 95% CI: −1.81–−0.39) and reduction of falls were greater after interventions with Tai Chi plus medication. Satisfaction and safety were high. Intervention with Tai Chi alone was more effective for only a few balance and mobility outcomes. Conclusions Tai Chi performed with medication resulted in promising gains in mobility and balance, and it was safe and popular among PD patients at an early stage of the disease. This provides a new evidence for PD management. More RCTs with larger sample size that carefully address blinding and prudently select outcomes are needed. PROSPERO registration number CRD42013004989. PMID:24927169

76 FR 17414 - Agency Information Collection Activities; Proposed Collection; Comment Request; 2011 Hazardous...

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2012-04-01

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