Tentative civil airworthiness flight criteria for powered-lift transports

NASA Technical Reports Server (NTRS)

Hynes, C. S.; Scott, B. C.

1976-01-01

Representatives of the U.S., British, French, and Canadian airworthiness authorities participated in a NASA/FAA program to formulate tentative civil airworthiness flight criteria for powered-lift transports. The ultimate limits of the flight envelope are defined by boundaries in the airspeed/path-angle plane. Angle of attack and airspeed margins applied to these ultimate limits provide protection against both atmospheric disturbances and disturbances resulting from pilot actions or system variability, but do not ensure maneuvering capability directly, as the 30% speed margin does for conventional transports. Separate criteria provide for direct demonstration of adequate capability for approach path control, flare and landing, and for go-around. Demonstration maneuvers are proposed, and appropriate abuses and failures are suggested. Taken together, these criteria should permit selection of appropriate operating points within the flight envelopes for the approach, landing, and go-around flight phases which are likely to be most critical for powered-lift aircraft.

Energy data report: prices and margins of No. 2 distillate fuel oil. Monthly report, January 1982

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

Whatley, A.

1982-03-22

Data are presented on the average prices and gross margins for the refining, reselling, and retailing sectors of the No. 2 distillate fuel oil market. Data are tabulated on prices and sales volumes of No. 2 fuel oil and No. 2 diesel fuel for residential, industrial/commercial, institutional/utility, other ultimate consumer sales, and nonultimate consumer sales. A brief discussion of the sampling and estimation procedures used in this report appears in the appendix.

Energy data report: prices and margins of No. 2 distillate fuel oil. Monthly report, October 1982

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

Whatley, A.

1982-12-20

Data are presented on the average prices and gross margins for the refining, reselling, and retailing sectors of the No. 2 distillate fuel oil market. Data are tabulated on prices and sales volumes of No. 2 fuel oil and No. 2 diesel fuel for residential, industrial/commercial, institutional/utility, other ultimate consumer sales, and nonultimate consumer sales. A brief discussion of the sampling and estimation procedures used in this report appears in the appendix.

Energy data report: prices and margins of No. 2 distillate fuel oil. Monthly report, November 1982

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

Whatley, A.

1983-01-18

Data are presented on the average prices and gross margins for the refining, reselling, and retailing sectors of the No. 2 distillate fuel oil market. Data are tabulated on prices and sales volumes of No. 2 fuel oil and No. 2 diesel fuel for residential, industrial/commercial, institutional/utility, other ultimate consumer sales, and nonultimate consumer sales. A brief discussion of the sampling and estimation procedures used in this report appears in the appendix.

Energy data report: prices and margins of No. 2 distillate fuel oil. Monthly report, December 1981

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

Whatley, A.

1982-02-22

Data are presented on the average prices and gross margins for the refining, reselling, and retailing sectors of the No. 2 distillate fuel oil market. Data are tabulated on prices and sales volumes of No. 2 fuel oil and No. 2 diesel fuel for residential, industrial/commercial, institutional/utility, other ultimate consumer sales, and nonultimate consumer sales. A brief discussion of the sampling and estimation procedures used in this report appears in the appendix.

Marginal and internal fit of CAD-CAM-fabricated composite resin and ceramic crowns scanned by 2 intraoral cameras.

PubMed

de Paula Silveira, Alessandra C; Chaves, Sacha B; Hilgert, Leandro A; Ribeiro, Ana Paula D

2017-03-01

The precision of fit of chairside computer-aided design and computer-aided manufacturing (CAD-CAM) complete crowns is affected by digital impression and restorative material. The purpose of this in vitro study was to evaluate by microcomputed tomography (μCT) the marginal and internal adaptation of composite resin and ceramic complete crowns fabricated with 2 different intraoral cameras and 2 restorative materials. Ten extracted human third molars received crown preparations. For each prepared molar, 2 digital impressions were made with different intraoral cameras of the CEREC system, Bluecam and Omnicam. Four groups were formed: LB (Lava Ultimate+Bluecam), EB (Emax+Bluecam), LO (Lava Ultimate+Omnicam), and EO (Emax+Omnicam). Before measuring the precision of fit, all crowns were stabilized with a silicone material. Each unit (crown + prepared tooth) was imaged with μCT, and marginal and internal discrepancies were analyzed. For the 2D analysis, 120 measurements were made of each crown for marginal adaptation, 20 for marginal discrepancy (MD), and 20 for absolute marginal discrepancy (AMD); and for internal adaptation, 40 for axial space (AS) and 40 for occlusal space (OS). After reconstructing the 3D images, the average internal space (AIS) was calculated by dividing the total volume of the internal space by the contact surface. Data were analyzed with 2-way ANOVA and quantile regression. Regarding marginal adaptation, no significant differences were observed among groups. For internal adaptation measured in the 2D evaluation, a significant difference was observed between LO and EO for the AS variable (Mann-Whitney test; P<.008). In assessment of AIS by the 3D reconstruction, LB presented significantly lower values than the other groups (Tukey post hoc test; P<.05). Bluecam presented lower values of AIS than Omnicam, and composite resin crowns showed less discrepancy than did ceramic crowns. The marginal adaptations assessed in all groups showed values within the clinically accepted range. Moreover, the composite resin blocks associated with the Bluecam intraoral camera demonstrated the best results for AIS compared with those of the other groups. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Sediment delivery to the Gulf of Alaska: source mechanisms along a glaciated transform margin

USGS Publications Warehouse

Dobson, M.R.; O'Leary, D.; Veart, M.

1998-01-01

Sediment delivery to the Gulf of Alaska occurs via four areally extensive deep-water fans, sourced from grounded tidewater glaciers. During periods of climatic cooling, glaciers cross a narrow shelf and discharge sediment down the continental slope. Because the coastal terrain is dominated by fjords and a narrow, high-relief Pacific watershed, deposition is dominated by channellized point-source fan accumulations, the volumes of which are primarily a function of climate. The sediment distribution is modified by a long-term tectonic translation of the Pacific plate to the north along the transform margin. As a result, the deep-water fans are gradually moved away from the climatically controlled point sources. Sets of abandoned channels record the effect of translation during the Plio-Pleistocene.

Structural design/margin assessment

NASA Technical Reports Server (NTRS)

Ryan, R. S.

1993-01-01

Determining structural design inputs and the structural margins following design completion is one of the major activities in space exploration. The end result is a statement of these margins as stability, safety factors on ultimate and yield stresses, fracture limits (fracture control), fatigue lifetime, reuse criteria, operational criteria and procedures, stability factors, deflections, clearance, handling criteria, etc. The process is normally called a load cycle and is time consuming, very complex, and involves much more than structures. The key to successful structural design is the proper implementation of the process. It depends on many factors: leadership and management of the process, adequate analysis and testing tools, data basing, communications, people skills, and training. This process and the various factors involved are discussed.

Decoupling of rotational and translational diffusion in supercooled colloidal fluids

PubMed Central

Edmond, Kazem V.; Elsesser, Mark T.; Hunter, Gary L.; Pine, David J.; Weeks, Eric R.

2012-01-01

We use confocal microscopy to directly observe 3D translational and rotational diffusion of tetrahedral clusters, which serve as tracers in colloidal supercooled fluids. We find that as the colloidal glass transition is approached, translational and rotational diffusion decouple from each other: Rotational diffusion remains inversely proportional to the growing viscosity whereas translational diffusion does not, decreasing by a much lesser extent. We quantify the rotational motion with two distinct methods, finding agreement between these methods, in contrast with recent simulation results. The decoupling coincides with the emergence of non-Gaussian displacement distributions for translation whereas rotational displacement distributions remain Gaussian. Ultimately, our work demonstrates that as the glass transition is approached, the sample can no longer be approximated as a continuum fluid when considering diffusion. PMID:23071311

40 CFR 86.412-78 - Maintenance instructions, submission to Administrator.

Code of Federal Regulations, 2010 CFR

2010-07-01

... systems. (2) Any revision to the maintenance instructions which will affect emissions shall be supplied to..., distributors, dealers, repair facilities, and ultimate purchasers. Any material not translated into the English...

Incidental Vocabulary Learning and Recall by Intermediate Foreign Language Students: The Influence of Marginal Glosses, Dictionary Use, and Summary Writing

ERIC Educational Resources Information Center

Ghabanchi, Zargham; Ayoubi, Elham Sadat

2012-01-01

This study is an attempt to compare the effect of four reading conditions on incidental vocabulary learning and recall of intermediate EFL learners. A sample population of 120 Iranian intermediate students read two short passages in one of four reading conditions: 1) L1 Marginal Glosses (MG1--provision of L1 translations of unknown words), 2) L2…

The Space That Difference Makes: On Marginality, Social Justice and the Future of the Health Humanities.

PubMed

Gutierrez, Kevin J; DasGupta, Sayantani

2016-12-01

Feminist theorist and educator, bell hooks, asserts that to seek true liberation one must choose marginality. One must choose to occupy the space outside the binary between colonizer-colonized, hegemonic center-periphery, and us-them in order to create a location of possibility. This essay will reveal the practice of social justice as the navigation of the space that difference makes and argue that choosing marginality provides a framework for health humanities work towards social justice in health care. The space of the launderette that is depicted in Hanif Kureishi's 1986 film, My Beautiful Laundrette, provides an example of choosing marginality and illustrates how difference structures both real and imagined spaces, which influences how individuals ultimately perceive one another. We will draw from the work of bell hooks; political geographer, Edward Soja; and Marxist philosopher, Henri Lefebvre, to demonstrate the importance of the health humanities' position at the margin to traditional health care education.

Translational informatics: an industry perspective.

PubMed

Cantor, Michael N

2012-01-01

Translational informatics (TI) is extremely important for the pharmaceutical industry, especially as the bar for regulatory approval of new medications is set higher and higher. This paper will explore three specific areas in the drug development lifecycle, from tools developed by precompetitive consortia to standardized clinical data collection to the effective delivery of medications using clinical decision support, in which TI has a major role to play. Advancing TI will require investment in new tools and algorithms, as well as ensuring that translational issues are addressed early in the design process of informatics projects, and also given higher weight in funding or publication decisions. Ultimately, the source of translational tools and differences between academia and industry are secondary, as long as they move towards the shared goal of improving health.

SU-F-J-24: Setup Uncertainty and Margin of the ExacTrac 6D Image Guide System for Patients with Brain Tumors

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

Kim, S; Oh, S; Yea, J

Purpose: This study evaluated the setup uncertainties for brain sites when using BrainLAB’s ExacTrac X-ray 6D system for daily pretreatment to determine the optimal planning target volume (PTV) margin. Methods: Between August 2012 and April 2015, 28 patients with brain tumors were treated by daily image-guided radiotherapy using the BrainLAB ExacTrac 6D image guidance system of the Novalis-Tx linear accelerator. DUONTM (Orfit Industries, Wijnegem, Belgium) masks were used to fix the head. The radiotherapy was fractionated into 27–33 treatments. In total, 844 image verifications were performed for 28 patients and used for the analysis. The setup corrections along with themore » systematic and random errors were analyzed for six degrees of freedom in the translational (lateral, longitudinal, and vertical) and rotational (pitch, roll, and yaw) dimensions. Results: Optimal PTV margins were calculated based on van Herk et al.’s [margin recipe = 2.5∑ + 0.7σ − 3 mm] and Stroom et al.’s [margin recipe = 2∑ + 0.7σ] formulas. The systematic errors (∑) were 0.72, 1.57, and 0.97 mm in the lateral, longitudinal, and vertical translational dimensions, respectively, and 0.72°, 0.87°, and 0.83° in the pitch, roll, and yaw rotational dimensions, respectively. The random errors (σ) were 0.31, 0.46, and 0.54 mm in the lateral, longitudinal, and vertical rotational dimensions, respectively, and 0.28°, 0.24°, and 0.31° in the pitch, roll, and yaw rotational dimensions, respectively. According to van Herk et al.’s and Stroom et al.’s recipes, the recommended lateral PTV margins were 0.97 and 1.66 mm, respectively; the longitudinal margins were 1.26 and 3.47 mm, respectively; and the vertical margins were 0.21 and 2.31 mm, respectively. Conclusion: Therefore, daily setup verifications using the BrainLAB ExacTrac 6D image guide system are very useful for evaluating the setup uncertainties and determining the setup margin.∑σ.« less

Adequate margins for random setup uncertainties in head-and-neck IMRT

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

Astreinidou, Eleftheria; Bel, Arjan; Raaijmakers, Cornelis P.J.

2005-03-01

Purpose: To investigate the effect of random setup uncertainties on the highly conformal dose distributions produced by intensity-modulated radiotherapy (IMRT) for clinical head-and-neck cancer patients and to determine adequate margins to account for those uncertainties. Methods and materials: We have implemented in our clinical treatment planning system the possibility of simulating normally distributed patient setup displacements, translations, and rotations. The planning CT data of 8 patients with Stage T1-T3N0M0 oropharyngeal cancer were used. The clinical target volumes of the primary tumor (CTV{sub primary}) and of the lymph nodes (CTV{sub elective}) were expanded by 0.0, 1.5, 3.0, and 5.0 mm inmore » all directions, creating the planning target volumes (PTVs). We performed IMRT dose calculation using our class solution for each PTV margin, resulting in the conventional static plans. Then, the system recalculated the plan for each positioning displacement derived from a normal distribution with {sigma} = 2 mm and {sigma} = 4 mm (standard deviation) for translational deviations and {sigma} = 1 deg for rotational deviations. The dose distributions of the 30 fractions were summed, resulting in the actual plan. The CTV dose coverage of the actual plans was compared with that of the static plans. Results: Random translational deviations of {sigma} = 2 mm and rotational deviations of {sigma} = 1 deg did not affect the CTV{sub primary} volume receiving 95% of the prescribed dose (V{sub 95}) regardless of the PTV margin used. A V{sub 95} reduction of 3% and 1% for a 0.0-mm and 1.5-mm PTV margin, respectively, was observed for {sigma} = 4 mm. The V{sub 95} of the CTV{sub elective} contralateral was approximately 1% and 5% lower than that of the static plan for {sigma} = 2 mm and {sigma} = 4 mm, respectively, and for PTV margins < 5.0 mm. An additional reduction of 1% was observed when rotational deviations were included. The same effect was observed for the CTV{sub elective} ipsilateral but with smaller dose differences than those for the contralateral side. The effect of the random uncertainties on the mean dose to the parotid glands was not significant. The maximal dose to the spinal cord increased by a maximum of 3 Gy. Conclusions: The margins to account for random setup uncertainties, in our clinical IMRT solution, should be 1.5 mm and 3.0 mm in the case of {sigma} = 2 mm and {sigma} = 4 mm, respectively, for the CTV{sub primary}. Larger margins (5.0 mm), however, should be applied to the CTV{sub elective}, if the goal of treatment is a V{sub 95} value of at least 99%.« less

Perspectives of Female African American Superintendents

ERIC Educational Resources Information Center

Bush, Rhea R.

2016-01-01

Gender, race, and class--intertwining oppressions experienced by Black women have ultimately led to barriers such as marginality, exploitation, political subjugation, and negative images of African American women (Collins, 2009). Research about the lived experiences of Black women has either been infrequently told or narrated by individuals who…

Mesozoic Continental Sediment-dispersal Systems of Mexico Linked to Development of the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Lawton, T. F.; Molina-Garza, R. S.; Barboza-Gudiño, R.; Rogers, R. D.

2013-05-01

Major sediment dispersal systems on western Pangea evolved in concert with thermal uplift, rift and drift phases of the Gulf of Mexico Basin, and were influenced by development of a continental arc on Pangea's western margin. Existing literature and preliminary data from fieldwork, sandstone petrology and detrital zircon analysis reveal how major drainages in Mexico changed from Late Triassic through Late Jurassic time and offer predictions for the ultimate destinations of sand-rich detritus along the Gulf and paleo-Pacific margins. Late Triassic rivers drained away from and across the present site of the Gulf of Mexico, which was then the location of a major thermal dome, the Texas uplift of recent literature. These high-discharge rivers with relatively mature sediment composition fed a large-volume submarine fan system on the paleo-Pacific continental margin of Mexico. Predictably, detrital zircon age populations are diverse and record sources as far away as the Amazonian craton. This enormous fluvial system was cut off abruptly near the Triassic-Jurassic boundary by extensive reorganization of continental drainages. Early and Middle Jurassic drainage systems had local headwaters and deposited sediment in extensional basins associated with arc magmatism. Redbeds accumulated across northern and eastern Mexico and Chiapas in long, narrow basins whose locations and dimensions are recorded primarily by inverted antiformal massifs. The Jurassic continental successions overlie Upper Triassic strata and local subvolcanic plutons; they contain interbedded volcanic rocks and thus have been interpreted as part of the Nazas continental-margin arc. The detritus of these fluvial systems is volcanic-lithic; syndepositional grain ages are common in the detrital zircon populations, which are mixed with Oaxaquia-derived Permo-Triassic and Grenville age populations. By this time, interior Pangea no longer supplied sediment to the paleo-Pacific margin, possibly because the continental-margin arc blocked westward drainage and detritus was captured in rift basins. Latest Middle Jurassic fluvial systems formed as the Yucatan block rotated counterclockwise and the Gulf of Mexico began to open. Sediment dispersal, partly equivalent to salt deposition in the Gulf, was largely southward in southern Oaxaquia, but large-volume braided river systems on the Maya (Yucatan) block, represented by the Todos Santos Formation in Chiapas, evidently flowed northward along graben axes toward the western part of the Gulf of Mexico Basin. River systems of nuclear Mexico, or Oaxaquia, occupied a broad sedimentary basin west and south of a divide formed adjacent to the translating Maya block. Despite their big-river characteristics, these deposits contain mainly Grenville and Permo-Triassic grains derived from Oaxaquia basement and subordinate Early and Middle Jurassic grains derived from volcanic rocks and plutons of the arc. Early Late Jurassic (Oxfordian) marine flooding of the entire Gulf rim and nuclear Mexico, evidently resulting in part from marginal subsidence adjoining newly-formed oceanic crust, terminated fluvial deposition adjacent to the young Gulf of Mexico.

Translation, Cultural Adaptation and Validation of the Simple Shoulder Test to Spanish

PubMed Central

Arcuri, Francisco; Barclay, Fernando; Nacul, Ivan

2015-01-01

Background: The validation of widely used scales facilitates the comparison across international patient samples. Objective: The objective was to translate, culturally adapt and validate the Simple Shoulder Test into Argentinian Spanish. Methods: The Simple Shoulder Test was translated from English into Argentinian Spanish by two independent translators, translated back into English and evaluated for accuracy by an expert committee to correct the possible discrepancies. It was then administered to 50 patients with different shoulder conditions.Psycometric properties were analyzed including internal consistency, measured with Cronbach´s Alpha, test-retest reliability at 15 days with the interclass correlation coefficient. Results: The internal consistency, validation, was an Alpha of 0,808, evaluated as good. The test-retest reliability index as measured by intra-class correlation coefficient (ICC) was 0.835, evaluated as excellent. Conclusion: The Simple Shoulder Test translation and it´s cultural adaptation to Argentinian-Spanish demonstrated adequate internal reliability and validity, ultimately allowing for its use in the comparison with international patient samples.

What is the role of culture, diversity, and community engagement in transdisciplinary translational science?

PubMed

Graham, Phillip W; Kim, Mimi M; Clinton-Sherrod, A Monique; Yaros, Anna; Richmond, Alan N; Jackson, Melvin; Corbie-Smith, Giselle

2016-03-01

Concepts of culture and diversity are necessary considerations in the scientific application of theory generation and developmental processes of preventive interventions; yet, culture and/or diversity are often overlooked until later stages (e.g., adaptation [T3] and dissemination [T4]) of the translational science process. Here, we present a conceptual framework focused on the seamless incorporation of culture and diversity throughout the various stages of the translational science process (T1-T5). Informed by a community-engaged research approach, this framework guides integration of cultural and diversity considerations at each phase with emphasis on the importance and value of "citizen scientists" being research partners to promote ecological validity. The integrated partnership covers the first phase of intervention development through final phases that ultimately facilitate more global, universal translation of changes in attitudes, norms, and systems. Our comprehensive model for incorporating culture and diversity into translational research provides a basis for further discussion and translational science development.

Translation and rotation of small crustal blocks in the southernmost Atlantic-Weddell Sea region prior to seafloor spreading: in search of a mechanism

NASA Astrophysics Data System (ADS)

Dalziel, I. W. D.; Norton, I. O.; Lawver, L. A.; Lavier, L.; Davis, J. K.; Gahagan, L.

2016-12-01

Geological and paleomagnetic data indicate that initial fragmentation of the Gondwanaland supercontinent in the southernmost Atlantic-Weddell Sea region involved translation and rotation of two small crustal blocks. The Falkland/Malvinas block on the South American plate (F/M) and the Ellsworth-Whitmore mountains block in West Antarctica (EWM) both contain segments of the earliest Mesozoic Gondwana fold belt. The blocks originated in the Natal embayment between the Cape Mountains of southernmost Africa and the Pensacola Mountains of the East Antarctic craton margin. Shortly after emplacement of the Karoo-Ferrar large igneous province (LIP) at ca. 182Ma, the F/M block was rotated clockwise 150 ° and the EWM block counter¬clockwise 90°, while both were translated several hundred kilometers towards the Panthalassic/Pacific Ocean. As indicated by absence of shortening in the sedimentary basins of the F/M Plateau and Weddell embayment, the motions of the crustal blocks relative to the major continents happened during extreme extension accompanied by widespread silicic magmatism that preceded seafloor spreading. We propose a new reconstruction of the Gondwana craton margin, suggesting an original embayment between the Kalahari and East Antarctic cratons, and subsequent mirror-image clockwise (South America-F/M) and counterclockwise (Antarctic Peninsula-EWM) rotations prior to seafloor spreading in the Weddell Sea and South Atlantic.What geodynamic processes were involved in the significant rotations and translations of continental lithosphere prior to ocean basin formation? Our conclusion, based on the geologic and geophysical data and on geodynamic modeling, is that the motions were driven by the distributed crustal thinning of warm continental lithosphere and by mantle flow towards a retreating Panthalassic margin subduction zone associated with the formation of the Karoo-Ferrar Large Igneous Province between the East Antarctic, Kalahari and Rio de la Plata cratons.

Cultural adaptation of the Tuberculosis-related stigma scale to Brazil.

PubMed

Crispim, Juliane de Almeida; Touso, Michelle Mosna; Yamamura, Mellina; Popolin, Marcela Paschoal; Garcia, Maria Concebida da Cunha; Santos, Cláudia Benedita Dos; Palha, Pedro Fredemir; Arcêncio, Ricardo Alexandre

2016-06-01

The process of stigmatization associated with TB has been undervalued in national research as this social aspect is important in the control of the disease, especially in marginalized populations. This paper introduces the stages of the process of cultural adaptation in Brazil of the Tuberculosis-related stigma scale for TB patients. It is a methodological study in which the items of the scale were translated and back-translated with semantic validation with 15 individuals of the target population. After translation, the reconciled back-translated version was compared with the original version by the project coordinator in Southern Thailand, who approved the final version in Brazilian Portuguese. The results of the semantic validation conducted with TB patients enable the identification that, in general, the scale was well accepted and easily understood by the participants.

Stress-mediated translational control in cancer cells.

PubMed

Leprivier, Gabriel; Rotblat, Barak; Khan, Debjit; Jan, Eric; Sorensen, Poul H

2015-07-01

Tumor cells are continually subjected to diverse stress conditions of the tumor microenvironment, including hypoxia, nutrient deprivation, and oxidative or genotoxic stress. Tumor cells must evolve adaptive mechanisms to survive these conditions to ultimately drive tumor progression. Tight control of mRNA translation is critical for this response and the adaptation of tumor cells to such stress forms. This proceeds though a translational reprogramming process which restrains overall translation activity to preserve energy and nutrients, but which also stimulates the selective synthesis of major stress adaptor proteins. Here we present the different regulatory signaling pathways which coordinate mRNA translation in the response to different stress forms, including those regulating eIF2α, mTORC1 and eEF2K, and we explain how tumor cells hijack these pathways for survival under stress. Finally, mechanisms for selective mRNA translation under stress, including the utilization of upstream open reading frames (uORFs) and internal ribosome entry sites (IRESes) are discussed in the context of cell stress. This article is part of a Special Issue entitled: Translation and Cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical nature of the light emitter of the Aequorea green fluorescent protein

PubMed Central

Niwa, Haruki; Inouye, Satoshi; Hirano, Takashi; Matsuno, Tatsuki; Kojima, Satoshi; Kubota, Masayuki; Ohashi, Mamoru; Tsuji, Frederick I.

1996-01-01

The jellyfish Aequorea victoria possesses in the margin of its umbrella a green fluorescent protein (GFP, 27 kDa) that serves as the ultimate light emitter in the bioluminescence reaction of the animal. The protein is made up of 238 amino acid residues in a single polypeptide chain and produces a greenish fluorescence (λmax = 508 nm) when irradiated with long ultraviolet light. The fluorescence is due to the presence of a chromophore consisting of an imidazolone ring, formed by a post-translational modification of the tripeptide -Ser65-Tyr66-Gly67-. GFP has been used extensively as a reporter protein for monitoring gene expression in eukaryotic and prokaryotic cells, but relatively little is known about the chemical mechanism by which fluorescence is produced. To obtain a better understanding of this problem, we studied a peptide fragment of GFP bearing the chromophore and a synthetic model compound of the chromophore. The results indicate that the GFP chromophore consists of an imidazolone ring structure and that the light emitter is the singlet excited state of the phenolate anion of the chromophore. Further, the light emission is highly dependent on the microenvironment around the chromophore and that inhibition of isomerization of the exo-methylene double bond of the chromophore accounts for its efficient light emission. PMID:8942983

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 04: Assessment of intra-fraction motion during lung SABR VMAT using a custom abdominal compression device

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

Hyde, Derek; Robinson, Mark; Araujo, Cynthia

2016-08-15

Purpose: Lung SABR patients are treated using Volumetrically Modulated Arc Therapy (VMAT), utilizing 2 arcs with Conebeam CT (CBCT) image-guidance prior to each arc. Intra-fraction imaging can prolong treatment time (up to 20%), and the aim of this study is to determine if it is necessary. Methods: We utilize an in-house abdominal compression device to minimize respiratory motion, 4DCT to define the ITV, a 5 mm PTV margin and a 2–3 mm PRV margin. We treated 23 patients with VMAT, fifteen were treated to 48 Gy in 4 fractions, while eight were treated with up to 60 Gy in 8more » fractions. Intrafraction motion was assessed by the translational errors recorded for the second CBCT. Results: There was no significant difference (t-test, p=0.93) in the intra-fraction motion between the patients treated with 4 and 8 fractions, or between the absolute translations in each direction (ANOVA, p=0.17). All 124 intra-fraction CBCT images were analysed and 95% remained localized within the 5 mm PTV margin The mean magnitude of the vector displacement was 1.8 mm. Conclusions: For patients localized with an abdominal compression device, the intrafraction CBCT image may not be necessary, if it is only the tumor coverage that is of concern, as the patients are typically well within the 5 mm PTV margin. On the other hand, if there is a structure with a smaller PRV margin, an intrafraction CBCT is recommended to ensure that the dose limit for the organ at risk is not exceeded.« less

Effect of different resin luting cements on the marginal fit of lithium disilicate pressed crowns.

PubMed

Mounajjed, Radek; Salinas, Thomas J; Ingr, Tomas; Azar, Basel

2017-11-15

The vertical marginal discrepancy of restorations can increase upon cementation, and poor marginal fit can lead to cement dissolution, marginal discoloration, microleakage, and secondary caries. The amount of increase is related to the type of luting cement used, but how lithium disilicate pressed crowns are affected by different resin cements is unclear. The purpose of this in vitro study was to compare the effect of using different resin luting cements on the vertical marginal discrepancy of lithium disilicate pressed crowns. A total of 18 intact extracted mandibular third molars were disinfected in a solution of 10% formalin for 7 days and were then prepared to receive a ceramic crown. Impressions were made with polyvinyl siloxane and lithium disilicate pressed crowns made and cemented with 1 of 3 resin luting cements. The marginal discrepancy was measured at 4 points on the finishing line of each tooth, with optical microscopy at ×200 magnification before and after cementation. Statistical analysis was done with the Kruskal-Wallis test to compare the median marginal increase among the 3 groups. The least amount of marginal increase after cementation was with Harvard PremiumFlow cement, with an average marginal increase of 42 ±11 μm. RelyX Ultimate cement increased the margins by an average 45 ±29 μm. The highest marginal increase was found in the Enamel Plus HRi preheated composite resin group (116 ±47 μm). The marginal increase of pressed crowns cemented with preheated composite resin (Enamel Plus HRi) exceeded the clinically acceptable range of marginal discrepancy. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Retention Strength of PMMA/UDMA-Based Crowns Bonded to Dentin: Impact of Different Coupling Agents for Pretreatment

PubMed Central

Stawarczyk, Bogna; Teuss, Simona; Eichberger, Marlis; Roos, Malgorzata; Keul, Christine

2015-01-01

Computer aided design/computer aided manufacturing (CAD/CAM) polymers for long-term dental restorations benefit from enhanced mechanical properties. However, the quantification of their bonding properties on teeth is lacking. Therefore, the aim of this study was to determine the retention strength (RS) of differently pretreated new developed polymethylmethacrylate/urethanedimethacrylate-based CAD/CAM polymer bonded on dentin. In summary, 120 human caries-free molars were prepared, and polymeric crowns were milled and pretreated (n = 20): visio.link (VL), Scotchbond Universal (SU), Monobond Plus/Heliobond (MH), Margin Bond (MB), Margin Bond mixed with acetone (1:1) (MBA) or not pretreated (CG). Half of the specimens were cemented using Variolink II and the other half with RelyX Ultimate. Specimens were stored for 24 h in distilled water and thermal cycled (5000 ×, 5 °C/55 °C). The retention load was measured and failure types were defined. RS was calculated and analyzed using both two- and one-way ANOVA with a post-hoc Scheffé-test, unpaired t-test, Kaplan–Meier with Breslow–Gehan test and chi-squared test (p < 0.05). Crowns bonded using RelyX Ultimate showed higher RS than those bonded using Variolink II. The pretreatment showed no impact on the RS. However, survival analysis within Variolink II found an impact of pretreatment. The median RS for MH was the lowest and statistically different from MB, MBA and CG. For Variolink II MH had the poorest survival as the estimated cumulative failure function of the debonded crown increased very quickly with increasing TBS. Within the RelyX Ultimate groups, no significant differences were determined. The newly developed CAD/CAM polymer showed the highest bonding properties after cementation using RelyX Ultimate. PMID:28793651

The Common Core "State" Standards: The Arts and Education Reform

ERIC Educational Resources Information Center

Wexler, Alice

2014-01-01

In this commentary, Alice Wexler notes that as the Common Core State Standards (CCSS) become reality, teachers have reason for concern. She contends that this reform to public education has consequently marginalized the arts and exacerbated the inequities of people in poverty and those with disabilities. Teachers, principals and, ultimately,…

A Nation at Risk to Win the Future: The State of Public Education in the U.S.

ERIC Educational Resources Information Center

Scott, Timothy

2011-01-01

Mounting evidence is exposing how merit pay incentives, charter schools, vocational curriculum, and high-stakes testing regimes do not fulfill their purported objectives, and instead are enormously detrimental to students, education workers, marginalized groups, social equality and ultimately the collective good. While the wealthy continue to…

Minimum Wage Effects throughout the Wage Distribution

ERIC Educational Resources Information Center

Neumark, David; Schweitzer, Mark; Wascher, William

2004-01-01

This paper provides evidence on a wide set of margins along which labor markets can adjust in response to increases in the minimum wage, including wages, hours, employment, and ultimately labor income. Not surprisingly, the evidence indicates that low-wage workers are most strongly affected, while higher-wage workers are little affected. Workers…

Breaking Free of Sample Size Dogma to Perform Innovative Translational Research

PubMed Central

Bacchetti, Peter; Deeks, Steven G.; McCune, Joseph M.

2011-01-01

Innovative clinical and translational research is often delayed or prevented by reviewers’ expectations that any study performed in humans must be shown in advance to have high statistical power. This supposed requirement is not justifiable and is contradicted by the reality that increasing sample size produces diminishing marginal returns. Studies of new ideas often must start small (sometimes even with an N of 1) because of cost and feasibility concerns, and recent statistical work shows that small sample sizes for such research can produce more projected scientific value per dollar spent than larger sample sizes. Renouncing false dogma about sample size would remove a serious barrier to innovation and translation. PMID:21677197

Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS.

PubMed

Otto, Markus; Bowser, Robert; Turner, Martin; Berry, James; Brettschneider, Johannes; Connor, James; Costa, Júlia; Cudkowicz, Merit; Glass, Jonathan; Jahn, Olaf; Lehnert, Stefan; Malaspina, Andrea; Parnetti, Lucilla; Petzold, Axel; Shaw, Pamela; Sherman, Alexander; Steinacker, Petra; Süssmuth, Sigurd; Teunissen, Charlotte; Tumani, Hayrettin; Wuolikainen, Anna; Ludolph, Albert

2012-01-01

Despite major advances in deciphering the neuropathological hallmarks of amyotrophic lateral sclerosis (ALS), validated neurochemical biomarkers for monitoring disease activity, earlier diagnosis, defining prognosis and unlocking key pathophysiological pathways are lacking. Although several candidate biomarkers exist, translation into clinical application is hindered by small sample numbers, especially longitudinal, for independent verification. This review considers the potential routes to the discovery of neurochemical markers in ALS, and provides a consensus statement on standard operating procedures that will facilitate multicenter collaboration, validation and ultimately clinical translation.

Double-Row Capsulolabral Repair Increases Load to Failure and Decreases Excessive Motion.

PubMed

McDonald, Lucas S; Thompson, Matthew; Altchek, David W; McGarry, Michelle H; Lee, Thay Q; Rocchi, Vanna J; Dines, Joshua S

2016-11-01

Using a cadaver shoulder instability model and load-testing device, we compared biomechanical characteristics of double-row and single-row capsulolabral repairs. We hypothesized a greater reduction in glenohumeral motion and translation and a higher load to failure in a mattress double-row capsulolabral repair than in a single-row repair. In 6 matched pairs of cadaveric shoulders, a capsulolabral injury was created. One shoulder was repaired with a single-row technique, and the other with a double-row mattress technique. Rotational range of motion, anterior-inferior translation, and humeral head kinematics were measured. Load-to-failure testing measured stiffness, yield load, deformation at yield load, energy absorbed at yield load, load to failure, deformation at ultimate load, and energy absorbed at ultimate load. Double-row repair significantly decreased external rotation and total range of motion compared with single-row repair. Both repairs decreased anterior-inferior translation compared with the capsulolabral-injured condition, however, no differences existed between repair types. Yield load in the single-row group was 171.3 ± 110.1 N, and in the double-row group it was 216.1 ± 83.1 N (P = .02). Ultimate load to failure in the single-row group was 224.5 ± 121.0 N, and in the double-row group it was 373.9 ± 172.0 N (P = .05). Energy absorbed at ultimate load in the single-row group was 1,745.4 ± 1,462.9 N-mm, and in the double-row group it was 4,649.8 ± 1,930.8 N-mm (P = .02). In cases of capsulolabral disruption, double-row repair techniques may result in decreased shoulder rotational range of motion and improved load-to-failure characteristics. In cases of capsulolabral disruption, repair techniques with double-row mattress repair may provide more secure fixation. Double-row capsulolabral repair decreases shoulder motion and increases load to failure, yield load, and energy absorbed at yield load more than single-row repair. Published by Elsevier Inc.

Translational research: understanding the continuum from bench to bedside.

PubMed

Drolet, Brian C; Lorenzi, Nancy M

2011-01-01

The process of translating basic scientific discoveries to clinical applications, and ultimately to public health improvements, has emerged as an important, but difficult, objective in biomedical research. The process is best described as a "translation continuum" because various resources and actions are involved in this progression of knowledge, which advances discoveries from the bench to the bedside. The current model of this continuum focuses primarily on translational research, which is merely one component of the overall translation process. This approach is ineffective. A revised model to address the entire continuum would provide a methodology to identify and describe all translational activities (eg, implementation, adoption translational research, etc) as well their place within the continuum. This manuscript reviews and synthesizes the literature to provide an overview of the current terminology and model for translation. A modification of the existing model is proposed to create a framework called the Biomedical Research Translation Continuum, which defines the translation process and describes the progression of knowledge from laboratory to health gains. This framework clarifies translation for readers who have not followed the evolving and complicated models currently described. Authors and researchers may use the continuum to understand and describe their research better as well as the translational activities within a conceptual framework. Additionally, the framework may increase the advancement of knowledge by refining discussions of translation and allowing more precise identification of barriers to progress. Copyright © 2011 Mosby, Inc. All rights reserved.

Mapping the Margins in Higher Education: On the Promise of Intersectionality Frameworks in Research and Discourse

ERIC Educational Resources Information Center

Museus, Samuel D.; Griffin, Kimberly A.

2011-01-01

"Intersectionality" can be defined as the "relationships among multiple social dimensions and modalities of social relations and subject formations." In simpler terms, it can be defined as the processes through which multiple social identities converge and ultimately shape individual and group experiences. In this article, the authors discuss the…

Potential Applications of Power Load Margin Theory for Women with Tenure in Higher Education

ERIC Educational Resources Information Center

Salyer-Funk, Amanda

2012-01-01

The purpose of this case study is to explore how tenured women with children describe their experiences; to discuss what institutional structures and policies they identify as influencing their advancement; and to see what they identify as the benefits, rewards, challenges, and/or sacrifices related to having tenure. Ultimately, a collection of…

Health literacy lost in translations? Introducing the European Health Literacy Glossary.

PubMed

Sørensen, Kristine; Brand, Helmut

2014-12-01

Health literacy has gained momentum in the Western world, yet in Europe the concept of health literacy is only marginally integrated in research, policy and practice. The present paper presents how translation may act as an influential factor with regard to integration of the health literacy notion in Europe. This study has compared five data sources that provide translations of health literacy: The European Union's Health Strategy; the translations applied in the European Health Literacy Project; national health expert opinions and Google Translate. The comparison integrated Peter Fawcett's translation techniques as a framework for analysis. The results showed a total of 28 translations: 22 from the European Union Health Strategy; 6 from the HLS-EU project; 17 from experts; 25 from Google Translate. Some countries are consistent in translations of health literacy, other countries diverge, the reasons being that health literacy is not yet mainstreamed and the translations are primarily driven by a latent polarized discourse of the concept of literacy. The study showed that translations in general reveals enriched insights in the cohesion of health literacy as one notion and provides the European Health Literacy Glossary that can inform health professionals, academia and decision-makers to further advance health literacy across Europe. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The ever-evolving role of mTOR in translation.

PubMed

Fonseca, Bruno D; Smith, Ewan M; Yelle, Nicolas; Alain, Tommy; Bushell, Martin; Pause, Arnim

2014-12-01

Control of translation allows for the production of stoichiometric levels of each protein in the cell. Attaining such a level of fine-tuned regulation of protein production requires the coordinated temporal and spatial control of numerous cellular signalling cascades impinging on the various components of the translational machinery. Foremost among these is the mTOR signalling pathway. The mTOR pathway regulates both the initiation and elongation steps of protein synthesis through the phosphorylation of numerous translation factors, while simultaneously ensuring adequate folding of nascent polypeptides through co-translational degradation of misfolded proteins. Perhaps most remarkably, mTOR is also a key regulator of the synthesis of ribosomal proteins and translation factors themselves. Two seminal studies have recently shown in translatome analysis that the mTOR pathway preferentially regulates the translation of mRNAs encoding ribosomal proteins and translation factors. Therefore, the role of the mTOR pathway in the control of protein synthesis extends far beyond immediate translational control. By controlling ribosome production (and ultimately ribosome availability), mTOR is a master long-term controller of protein synthesis. Herein, we review the literature spanning the early discoveries of mTOR on translation to the latest advances in our understanding of how the mTOR pathway controls the synthesis of ribosomal proteins. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Campaigning for Children's Oral Health: A Case Study

ERIC Educational Resources Information Center

Vaughan, Kate

2009-01-01

Arguably, the ultimate application of evidenced-based communications is translating the research recommendations into a full-fledged media campaign. This article explains the development and implementation of Watch Your Mouth, a campaign based on FrameWorks Institute's research on children's oral health. To date, this innovative campaign has been…

Shelf-geometry response to changes in relative sea level on a mixed carbonate siliciclastic shelf in the Guyana Basin

NASA Astrophysics Data System (ADS)

Campbell, A. Ewan

2005-04-01

Differences in the shelf-margin geometry for various depositional regimes show how siliciclastic and carbonate margins respond differently to changes in accommodation space. During the Cenozoic, sequences of carbonate and siliciclastic sediment were deposited in the Guyana Basin on the passive continental margin of NE South America. Study of the sequence geometries reveal significantly different geometric responses to changes in relative sea level of intervals dominated by carbonates to intervals dominated by siliciclastics. Using the geometrical shelf break as a reference point, aggradation and progradation rates for the carbonate and siliciclastic depositional systems were measured. In siliciclastics, the lateral position of the margin remains roughly stationary with relative sea-level rises in the order of 30 m/My. At higher rates the margin retreats at lower rates it progrades. Carbonate margins remain stationary or slightly progradational even with relative sea-level rises of up to 100 m/My, the fastest rates observed in this study. This illustrates the strong tendency of carbonate platforms to stack their margins and keep up with relative rises in sea level, rather than gradually retreat landward as do siliciclastics. This observation may explain why carbonate platforms preferentially try to defend a margin prior to ultimate backstepping. The high aggradation potential of carbonate margins also gives onlap and downlap termination patterns on seismic profiles where carbonate platforms develop on sloping siliciclastic shelves. The resulting unconformities are a result of differences in sediment dispersal between the two systems and not necessarily from changes of relative sea level.

Neogene rotations and quasicontinuous deformation of the Pacific Northwest continental margin

USGS Publications Warehouse

England, Philip; Wells, Ray E.

1991-01-01

Paleomagnetically determined rotations about vertical axes of 15 to 12 Ma flows of the Miocene Columbia River Basalt Group of Oregon and Washington decrease smoothly with distance from the plate margin, consistent with a simple physical model for continental deformation that assumes the lithosphere behaves as a thin layer of fluid. The average rate of northward translation of the continental margin since 15 Ma calculated from the rotations, using this model, is about 15 mm/yr, which suggests that much of the tangential motion between the Juan de Fuca and North American plates since middle Miocene time has been taken up by deformation of North America. The fluid-like character of the large-scale deformation implies that the brittle upper crust follows the motions of the deeper parts of the lithosphere.

Home-Schooled Students Rise in Supply and Demand

ERIC Educational Resources Information Center

Wasley, Paula

2007-01-01

The home-school movement, a once-marginalized segment of the educational community, is all grown up and going off to college. As colleges across the nation report increasing numbers of applications from home-schooled students, policies have been developed to evaluate these candidates. Translating years of independent study into something that…

Priority-setting in New Zealand: translating principles into practice.

PubMed

Ashton, T; Cumming, J; Devlin, N

2000-07-01

In May 1998 the New Zealand Health Funding Authority released a discussion paper which proposed a principles-based approach to setting purchasing priorities that incorporates the economic methods of programme budgeting and marginal analysis, and cost-utility analysis. The principles upon which the process was to be based are effectiveness, cost, equity of health outcomes, Maori health and acceptability. This essay describes and critiques issues associated with translating the principles into practice, most particularly the proposed methods for evaluating the effectiveness and measuring the cost of services. It is argued that the proposals make an important contribution towards the development of a method for prioritizing services which challenges our thinking about those services and their goals, and which is systematic, explicit, and transparent. The shift towards 'thinking at the margin' and systematically reviewing the value for money of competing claims on resources is likely to improve the quality of decision-making compared with the status quo. This does not imply that prioritization can, or should, be undertaken by means of any simple formula. Any prioritization process should always be guided by informed judgement. The approach is more appropriate for some services than for others. Key methodological issues that need further consideration include the choice of instrument for measuring health gains, the identification of marginal services, how to combine qualitative and quantitative information, and how to ensure consistency across different levels of decision-making.

Marginal adaptation of composite resins under two adhesive techniques.

PubMed

Dačić, Stefan; Veselinović, Aleksandar M; Mitić, Aleksandar; Nikolić, Marija; Cenić, Milica; Dačić-Simonović, Dragica

2016-11-01

In the present research, different adhesive techniques were used to set up fillings with composite resins. After the application of etch and rinse or self etch adhesive technique, marginal adaptation of composite fillings was estimated by the length of margins without gaps, and by the microretention of resin in enamel and dentin. The study material consisted of 40 extracted teeth. Twenty Class V cavities were treated with 35% phosphorous acid and restored after rinsing by Adper Single Bond 2 and Filtek Ultimate-ASB/FU 3M ESPE composite system. The remaining 20 cavities were restored by Adper Easy One-AEO/FU 3M ESPE composite system. Marginal adaptation of composite fillings was examined using a scanning electron microscope (SEM). The etch and rinse adhesive technique showed a significantly higher percentage of margin length without gaps (in enamel: 92.5%, in dentin: 57.3%), compared with the self-etch technique with lower percentage of margin length without gaps, in enamel 70.4% (p < .001), and in dentin-22.6% (p < .05). In the first technique, microretention was composed of adhesive and hybrid layers as well as resin tugs in interprismatic spaces of enamel, while the dentin microretention was composed of adhesive and hybrid layers with resin tugs in dentin canals. In the second technique, resin tugs were rarely seen and a microgap was dominant along the border of restoration margins. The SEM analysis showed a better marginal adaptation of composite resin to enamel and dentin with better microretention when the etch and rinse adhesive procedure was applied. © 2016 Wiley Periodicals, Inc.

Translational medicine: science or wishful thinking?

PubMed Central

Wehling, Martin

2008-01-01

"Translational medicine" as a fashionable term is being increasingly used to describe the wish of biomedical researchers to ultimately help patients. Despite increased efforts and investments into R&D, the output of novel medicines has been declining dramatically over the past years. Improvement of translation is thought to become a remedy as one of the reasons for this widening gap between input and output is the difficult transition between preclinical ("basic") and clinical stages in the R&D process. Animal experiments, test tube analyses and early human trials do simply not reflect the patient situation well enough to reliably predict efficacy and safety of a novel compound or device. This goal, however, can only be achieved if the translational processes are scientifically backed up by robust methods some of which still need to be developed. This mainly relates to biomarker development and predictivity assessment, biostatistical methods, smart and accelerated early human study designs and decision algorithms among other features. It is therefore claimed that a new science needs to be developed called 'translational science in medicine'. PMID:18559092

Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

PubMed

Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

2014-05-06

Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

The Privileging of Communitarian Ideas: Citation Practices and the Translation of Social Capital Into Public Health Research

PubMed Central

Moore, Spencer; Shiell, Alan; Hawe, Penelope; Haines, Valerie A.

2005-01-01

The growing use of social science constructs in public health invites reflection on how public health researchers translate, that is, appropriate and reshape, constructs from the social sciences. To assess how 1 recently popular construct has been translated into public health research, we conducted a citation network and content analysis of public health articles on the topic of social capital. The analyses document empirically how public health researchers have privileged communitarian definitions of social capital and marginalized network definitions in their citation practices. Such practices limit the way public health researchers measure social capital’s effects on health. The application of social science constructs requires that public health scholars be sensitive to how their own citation habits shape research and knowledge. PMID:16006421

If brands are built over years, why are they managed over quarters?

PubMed

Lodish, Leonard M; Mela, Carl F

2007-01-01

Brands are on the wane. Many consumer-goods companies blame the big-box discount retailers, but the Wharton School's Leonard Lodish and the Fuqua School's Carl Mela have a different explanation. Their research suggests that companies have damaged their brands by investing too much in short-term price promotions and too little in long-term brand building. To rescue their brands and increase profitability, corporate managers must arm themselves with long-term measures of brand performance and use them to make smarter marketing decisions. Several factors explain the short-sightedness of brand management: the increased availability of weekly, or even hourly, scanner data, which show a clear link between discounts and immediate boosts in sales; the relative difficulty of measuring the effects of advertising, new-product development, and distribution--all of which can contribute to a brand's long-term health; the short tenure of most brand managers; and the near-term orientation of Wall Street analysts. Although discounts do increase sales in the short-term, they ultimately lower profit margins. If a product is often discounted, consumers learn to buy it only when it's on sale. Moreover, when one firm increases its discounts, others usually follow suit, lowering everyone's margins. Executives can monitor a brand's long-term performance by watching a dashboard of measures. Only after examining such measures, for example, did managers at Clorox discover that the company's heavy discounting and decreased advertising had caused a steady decline in overall bleach sales and profit margins. In response, Clorox reduced discounting and increased television advertising, moves that ultimately strengthened the brand and reversed the firm's downward trends.

Do marginalized neighbourhoods have less healthy retail food environments? An analysis using Bayesian spatial latent factor and hurdle models.

PubMed

Luan, Hui; Minaker, Leia M; Law, Jane

2016-08-22

Findings of whether marginalized neighbourhoods have less healthy retail food environments (RFE) are mixed across countries, in part because inconsistent approaches have been used to characterize RFE 'healthfulness' and marginalization, and researchers have used non-spatial statistical methods to respond to this ultimately spatial issue. This study uses in-store features to categorize healthy and less healthy food outlets. Bayesian spatial hierarchical models are applied to explore the association between marginalization dimensions and RFE healthfulness (i.e., relative healthy food access that modelled via a probability distribution) at various geographical scales. Marginalization dimensions are derived from a spatial latent factor model. Zero-inflation occurring at the walkable-distance scale is accounted for with a spatial hurdle model. Neighbourhoods with higher residential instability, material deprivation, and population density are more likely to have access to healthy food outlets within a walkable distance from a binary 'have' or 'not have' access perspective. At the walkable distance scale however, materially deprived neighbourhoods are found to have less healthy RFE (lower relative healthy food access). Food intervention programs should be developed for striking the balance between healthy and less healthy food access in the study region as well as improving opportunities for residents to buy and consume foods consistent with dietary recommendations.

Contextual analysis and the success of translational research.

PubMed

Biglan, Anthony; Levin, Michael E

2016-03-01

The success of translational research can ultimately be judged by the degree to which it reduces the incidence and prevalence of psychological, behavioral, and physical disorders and the major factors influencing them. In our view, we currently place insufficient emphasis on assessing our impact on the social determinants of disorders. As a result, we are failing to affect the incidence and prevalence of critical disorders. Moreover, translational research fails to take into account the full range of interventions that could significantly reduce the incidence and prevalence of our most pressing disorders. These include policy changes, media, and broad cultural change movements. In this paper, we discuss the momentous achievements the tobacco prevention movement made over the last half-century, describe how the lessons gleaned from this success can apply to other prevention efforts, and contrast this success with progress made in battling other major public health concerns. We call for an expansion of the translational research agenda to develop and evaluate broader and more comprehensive strategies to affect well-being in entire populations.

Outward bound: women translators and scientific travel writing, 1780-1800.

PubMed

Martin, Alison E

2016-04-01

As the Enlightenment drew to a close, translation had gradually acquired an increasingly important role in the international circulation and transmission of scientific knowledge. Yet comparatively little attention has been paid to the translators responsible for making such accounts accessible in other languages, some of whom were women. In this article I explore how European women cast themselves as intellectually enquiring, knowledgeable and authoritative figures in their translations. Focusing specifically on the genre of scientific travel writing, I investigate the narrative strategies deployed by women translators to mark their involvement in the process of scientific knowledge-making. These strategies ranged from rhetorical near-invisibility, driven by women's modest marginalization of their own public engagement in science, to the active advertisement of themselves as intellectually curious consumers of scientific knowledge. A detailed study of Elizabeth Helme's translation of the French ornithologist François le Vaillant's Voyage dans l'intérieur de l'Afrique [Voyage into the Interior of Africa] (1790) allows me to explore how her reworking of the original text for an Anglophone reading public enabled her to engage cautiously - or sometimes more openly - with questions regarding how scientific knowledge was constructed, for whom and with which aims in mind.

Kreol: A Language Training Program for Peace Corps-Seychelles.

ERIC Educational Resources Information Center

Mancienne, Roger

A course in French-derived Kreol is designed for language learning among Peace Corps volunteers assigned to the Seychelles. The materials consist of 36 lessons on topics of daily communication needs. Lessons contain a story, dialogue, and/or list of expressions, exercises, and vocabulary and grammar notes and translations in the margin. Some…

The effect of uterine motion and uterine margins on target and normal tissue doses in intensity modulated radiation therapy of cervical cancer

NASA Astrophysics Data System (ADS)

Gordon, J. J.; Weiss, E.; Abayomi, O. K.; Siebers, J. V.; Dogan, N.

2011-05-01

In intensity modulated radiation therapy (IMRT) of cervical cancer, uterine motion can be larger than cervix motion, requiring a larger clinical target volume to planning target volume (CTV-to-PTV) margin around the uterine fundus. This work simulates different motion models and margins to estimate the dosimetric consequences. A virtual study used image sets from ten patients. Plans were created with uniform margins of 1 cm (PTVA) and 2.4 cm (PTVC), and a margin tapering from 2.4 cm at the fundus to 1 cm at the cervix (PTVB). Three inter-fraction motion models (MM) were simulated. In MM1, all structures moved with normally distributed rigid body translations. In MM2, CTV motion was progressively magnified as one moved superiorly from the cervix to the fundus. In MM3, both CTV and normal tissue motion were magnified as in MM2, modeling the scenario where normal tissues move into the void left by the mobile uterus. Plans were evaluated using static and percentile DVHs. For a conventional margin (PTVA), quasi-realistic uterine motion (MM3) reduces fundus dose by about 5 Gy and increases normal tissue volumes receiving 30-50 Gy by ~5%. A tapered CTV-to-PTV margin can restore fundus and CTV doses, but will increase normal tissue volumes receiving 30-50 Gy by a further ~5%.

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

PubMed Central

Brown, Sherry-Ann; McCullough, Louise D.; Loew, Leslie M.

2014-01-01

Hereditary ataxia, or motor incoordination, affects approximately 150,000 Americans and hundreds of thousands of individuals worldwide with onset from as early as mid-childhood. Affected individuals exhibit dysarthria, dysmetria, action tremor, and diadochokinesia. In this review, we consider an array of computational studies derived from experimental observations relevant to human neuropathology. A survey of related studies illustrates the impact of integrating clinical evidence with data from mouse models and computational simulations. Results from these studies may help explain findings in mice, and after extensive laboratory study, may ultimately be translated to ataxic individuals. This inquiry lays a foundation for using computation to understand neurobiochemical and electrophysiological pathophysiology of spinocerebellar ataxias and may contribute to development of therapeutics. The interdisciplinary analysis suggests that computational neurobiology can be an important tool for translational neurology. PMID:25653585

Commentary: Online Reviews and Other Digital Marketing Strategies.

PubMed

Levin, Roger P

2017-02-01

As getting patient reviews posted on online sites appears problematic for periodontal practices, the author urges periodontists to encourage patients to review their practices online on Yelp and other sites. The more positive online reviews practices receive, the higher the rankings on review sites, which will translate into more website visits and, ultimately, more new patient appointments.

Mashing up Multiple Web Feeds Using Yahoo! Pipes

ERIC Educational Resources Information Center

Fagan, Jody Condit

2007-01-01

Pipes is an interactive data aggregator and manipulator that lets you mashup your favorite online data sources. Pipes could be used to "combine many feeds into one, then sort, filter and translate to create your ultimate custom feed. In this article, the author describes how to use Yahoo! Pipes. The author shares what she has learned in…

[Medical big data and precision medicine: prospects of epidemiology].

PubMed

Song, J; Hu, Y H

2016-08-10

Since the development of high-throughput technology, electronic medical record system and big data technology, the value of medical data has caused more attention. On the other hand, the proposal of Precision Medicine Initiative opens up the prospect for medical big data. As a Tool-related Discipline, Epidemiology is, focusing on exploitation the resources of existing big data and promoting the integration of translational research and knowledge to completely unlocking the "black box" of exposure-disease continuum. It also tries to accelerating the realization of the ultimate goal on precision medicine. The overall purpose, however is to translate the evidence from scientific research to improve the health of the people.

Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

PubMed Central

Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

2015-01-01

Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

Estimation of the full marginal costs of port related truck traffic.

PubMed

Berechman, Joseph

2009-11-01

NY region is expected to grow by additional 1 million people by 2020, which translates into roughly 70 million more tons of goods to be delivered annually. Due to lack of rail capacity, mainly trucks will haul this volume of freight, challenging an already much constrained highway network. What are the total costs associated with this additional traffic, in particular, congestion, safety and emission? Since a major source of this expected flow is the Port of New York-New Jersey, this paper focuses on the estimation of the full marginal costs of truck traffic resulting from the further expansion of the port's activities.

Immobilisation precision in VMAT for oral cancer patients

NASA Astrophysics Data System (ADS)

Norfadilah, M. N.; Ahmad, R.; Heng, S. P.; Lam, K. S.; Radzi, A. B. Ahmad; John, L. S. H.

2017-05-01

A study was conducted to evaluate and quantify a precision of the interfraction setup with different immobilisation devices throughout the treatment time. Local setup accuracy was analysed for 8 oral cancer patients receiving radiotherapy; 4 with HeadFIX® mouthpiece moulded with wax (HFW) and 4 with 10 ml/cc syringe barrel (SYR). Each patients underwent Image Guided Radiotherapy (IGRT) with total of 209 cone-beam computed tomography (CBCT) data sets for position set up errors measurement. The setup variations in the mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) dimensions were measured. Overall mean displacement (M), the population systematic (Σ) and random (σ) errors and the 3D vector length were calculated. Clinical target volume to planning target volume (CTV-PTV) margins were calculated according to the van Herk formula (2.5Σ+0.7σ). The M values for both group were < 1 mm and < 1° in all translational and rotational directions. This indicate there is no significant imprecision in the equipment (lasers) and during procedure. The interfraction translational 3 dimension vector for HFW and SYR were 1.93±0.66mm and 3.84±1.34mm, respectively. The interfraction average rotational error were 0.00°±0.65° and 0.34°±0.59°, respectively. CTV-PTV margins along the 3 translational axis (Right-Left, Superior-Inferior, Anterior-Posterior) calculated were 3.08, 2.22 and 0.81 mm for HFW and 3.76, 6.24 and 5.06 mm for SYR. The results of this study have demonstrated that HFW more precise in reproducing patient position compared to conventionally used SYR (p<0.001). All margin calculated did not exceed hospital protocol (5mm) except S-I and A-P axes using syringe. For this reason, a daily IGRT is highly recommended to improve the immobilisation precision.

TU-F-CAMPUS-J-01: Inference of Prostate PTV Margins in VMAT Delivery From Intra-Fraction Prostate Motion During SBRT Delivery

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

Thind, K; Wong, R; Gerdes, C

2015-06-15

Purpose: To retrospectively quantify the intra-fraction prostate motion during stereotactic body radiation therapy (SBRT) treatment using CyberKnife’s target tracking system, which may provide insight into expansion margins from GTV to PTV used in gantry-based treatments. CyberKnife is equipped with an active tracking system (InTempo) that tracks the four fiducials placed in the prostate gland. The system acquires intra-fraction orthogonal kV images at 45° and 315° in a sequential fashion. Methods: A total of 38 patients treated with SBRT using CyberKnife between 2011 and 2013 were studied. Dose-regime was 36.25 Gy in 5 fractions (7.25 Gy/fraction, twice per week) as permore » RTOG 0938 guidelines. The CyberKnife image tracking logs for all SBRT treatments using InTempo were examined. A total of 13663 images were examined for the superior/inferior (SI), anterior/posterior (AP) and left/right (LR) translation as well as roll, pitch and yaw rotations for the target position relative to the last known model position. Results: The mean ± 2 SD of intra-fraction motion was contained within 3 mm for SI and LR and 4.5 mm for AP directions at 5 minutes into the treatment delivery. It was contained within 4 mm for SI and LR and 5 mm for AP at 10 minutes. At 15 minutes into delivery, all translations were contained within 5 mm. The mean ± 2 SD of prostate roll, pitch and yaw increased with time but were contained within 5 degree at 5, 10 and 15 minutes into treatment. Additionally, target translations and rotations were within ± 1 mm and ± 1 degree for 90% and 78% of the time. Conclusion: The organ motion component of PTV margin for 10 minute VMAT delivery is contained within 4 mm in SI and LR direction and within 5 mm in the AP direction.« less

Controls on continental strain partitioning above an oblique subduction zone, Northern Andes

NASA Astrophysics Data System (ADS)

Schütt, Jorina M.; Whipp, David M., Jr.

2016-04-01

Strain partitioning is a common process at obliquely convergent plate margins dividing oblique convergence into margin-normal slip on the plate-bounding fault and horizontal shearing on a strike-slip system parallel to the subduction margin. In subduction zones, strain partitioning in the upper continental plate is mainly controlled by the shear forces acting on the plate interface and the strength of the continental crust. The plate interface forces are influenced by the subducting plate dip angle and the obliquity angle between the normal to the plate margin and the convergence velocity vector, and the crustal strength of the continent is strongly affected by the presence or absence of a volcanic arc, with the presence of the volcanic arcs being common at steep subduction zones. Along the ˜7000 km western margin of South America the convergence obliquity, subduction dip angles and presence of a volcanic arc all vary, but strain partitioning is only observed along parts of it. This raises the questions, to what extent do subduction zone characteristics control strain partitioning in the overriding continental plate, and which factors have the largest influence? We address these questions using lithospheric-scale 3D numerical geodynamic experiments to investigate the influence of subduction dip angle, convergence obliquity, and weaknesses in the crust owing to the volcanic arc on strain partitioning behavior. We base the model design on the Northern Volcanic Zone of the Andes (5° N - 2° S), characterized by steep subduction (˜ 35°), a convergence obliquity between 31° -45° and extensive arc volcanism, and where strain partitioning is observed. The numerical modelling software (DOUAR) solves the Stokes flow and heat transfer equations for a viscous-plastic creeping flow to calculate velocity fields, thermal evolution, rock uplift and strain rates in a 1600 km x 1600 km box with depth 160 km. Subduction geometry and material properties are based on a simplified, generic subduction zone similar to the northern Andes. The upper surface is initially defined to resemble the Andes, but is free to deform during the experiments. We consider two main model designs, one with and one without a volcanic arc (weak continental zone). A relatively high angle of convergence obliquity is predicted to favor strain partitioning, but preliminary model results show no strain partitioning for a uniform continental crustal strength with a friction angle of Φ = 15° . However, strain partitioning does occur when including a weak zone in the continental crust resulting from arc volcanic activity with Φ = 5° . This results in margin-parallel northeastward translation of a continental sliver at 3.2 cm/year. The presence of the sliver agrees well with observations of a continental sliver identified by GPS measurements in the Northern Volcanic Zone with a translation velocity of about 1 cm/year, though the GPS-derived velocity may not be representative of the long-term rate of translation depending on whether the observation period includes one or more seismic cycles. Regardless, the observed behavior is consistent with the observed earthquake focal mechanisms and GPS measurements, suggesting significant northeastward transport of Andean crust along the margin of the northern Andes.

WSEAT Shock Testing Margin Assessment Using Energy Spectra Final Report.

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

Sisemore, Carl; Babuska, Vit; Booher, Jason

Several programs at Sandia National Laboratories have adopted energy spectra as a metric to relate the severity of mechanical insults to structural capacity. The purpose being to gain insight into the system's capability, reliability, and to quantify the ultimate margin between the normal operating envelope and the likely system failure point -- a system margin assessment. The fundamental concern with the use of energy metrics was that the applicability domain and implementation details were not completely defined for many problems of interest. The goal of this WSEAT project was to examine that domain of applicability and work out the necessarymore » implementation details. The goal of this project was to provide experimental validation for the energy spectra based methods in the context of margin assessment as they relate to shock environments. The extensive test results concluded that failure predictions using energy methods did not agree with failure predictions using S-N data. As a result, a modification to the energy methods was developed following the form of Basquin's equation to incorporate the power law exponent for fatigue damage. This update to the energy-based framework brings the energy based metrics into agreement with experimental data and historical S-N data.« less

Risk Belief and Attitude Formation From Translated Scientific Messages About PFOA, an Environmental Risk Associated With Breast Cancer.

PubMed

Smith, Sandi W; Hitt, Rose; Russell, Jessica; Nazione, Samantha; Silk, Kami; Atkin, Charles K; Keating, David

2017-03-01

Evidence regarding possible environmental causes of breast cancer is advancing. Often, however, the public is not informed about these advances in a manner that is easily understandable. This research translates findings from biologists into messages at two literacy levels about perfluorooctanoic acid (PFOA), a possible environmental contributor to breast cancer. The Heuristic Systematic Model (HSM) was used to investigate how ability, motivation, and systematic and heuristic processing lead to risk beliefs and, ultimately, to negative attitudes for individuals receiving translated scientific messages about PFOA. Participants (N = 1,389) came from the Dr. Susan Love Research Foundation's Army of Women. Findings indicated that ability, in the form of translated messages, predicted systematic processing, operationalized as knowledge gain, which was negatively associated with formation of risk beliefs that led to negative attitudes toward PFOA. Heuristic processing cues, operationalized as perceived message quality and source credibility, were positively associated with risk beliefs, which predicted negative attitudes about PFOA. Overall, more knowledge and lower literacy messages led to lower perceived risk, while greater involvement and ratings of heuristic cues led to greater risk perceptions. This is an example of a research, translation, and dissemination team effort in which biologists created knowledge, communication scholars translated and tested messages, and advocates were participants and those who disseminated messages.

Textual and Pictorial Glosses: Effectiveness on Incidental Vocabulary Growth When Reading in a Foreign Language.

ERIC Educational Resources Information Center

Kost, Claudia R.; Foss, Pamelo; Lenzini, John J.

1999-01-01

Investigates the effects of pictorial and textual glosses and a combination thereof on incidental vocabulary growth of foreign language learners. Subjects from second-semester German classes read a narrative text passage under one of three marginal gloss conditions: textual gloss (English translation); pictorial gloss; and text and pictures in the…

The Old Man and the Sea: Navigating the Gulf between Special Educators and the Content Area Classroom

ERIC Educational Resources Information Center

Kennedy, Michael J.; Ihle, Frances M.

2012-01-01

The special educator in the content area classroom often experiences an ill-defined role, which can translate into marginalization within instructional settings. Indeed, most students with learning disabilities (LD) receive content area instruction from a general education teacher with the support of a special educator. However, the literacy…

Reengineering the National Clinical and Translational Research Enterprise: The Strategic Plan of the National Clinical and Translational Science Awards Consortium

PubMed Central

Reis, Steven E.; Berglund, Lars; Bernard, Gordon R.; Califf, Robert M.; FitzGerald, Garret A.; Johnson, Peter C.

2009-01-01

Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process in turn depends upon observational data gathered from patients, communities, and public-health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation’s academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding. To address these serious and systemic problems, in 2006, the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program’s overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation’s academic health centers. PMID:20182119

Effective knowledge management in translational medicine.

PubMed

Szalma, Sándor; Koka, Venkata; Khasanova, Tatiana; Perakslis, Eric D

2010-07-19

The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health. The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern. The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface. The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.

Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

PubMed Central

Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

2014-01-01

Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

Signalling to eIF4E in cancer

PubMed Central

Siddiqui, Nadeem; Sonenberg, Nahum

2015-01-01

Translational control plays a critical role in the regulation of gene expression in eukaryotes and affects many essential cellular processes, including proliferation, apoptosis and differentiation. Under most circumstances, translational control occurs at the initiation step at which the ribosome is recruited to the mRNA. The eukaryotic translation initiation factor 4E (eIF4E), as part of the eIF4F complex, interacts first with the mRNA and facilitates the recruitment of the 40S ribosomal subunit. The activity of eIF4E is regulated at many levels, most profoundly by two major signalling pathways: PI3K (phosphoinositide 3-kinase)/Akt (also known and Protein Kinase B, PKB)/mTOR (mechanistic/mammalian target of rapamycin) and Ras (rat sarcoma)/MAPK (mitogen-activated protein kinase)/Mnk (MAPK-interacting kinases). mTOR directly phosphorylates the 4E-BPs (eIF4E-binding proteins), which are inhibitors of eIF4E, to relieve translational suppression, whereas Mnk phosphorylates eIF4E to stimulate translation. Hyperactivation of these pathways occurs in the majority of cancers, which results in increased eIF4E activity. Thus, translational control via eIF4E acts as a convergence point for hyperactive signalling pathways to promote tumorigenesis. Consequently, recent works have aimed to target these pathways and ultimately the translational machinery for cancer therapy. PMID:26517881

Reengineering the national clinical and translational research enterprise: the strategic plan of the National Clinical and Translational Science Awards Consortium.

PubMed

Reis, Steven E; Berglund, Lars; Bernard, Gordon R; Califf, Robert M; Fitzgerald, Garret A; Johnson, Peter C

2010-03-01

Advances in human health require the efficient and rapid translation of scientific discoveries into effective clinical treatments; this process, in turn, depends on observational data gathered from patients, communities, and public health research that can be used to guide basic scientific investigation. Such bidirectional translational science, however, faces unprecedented challenges due to the rapid pace of scientific and technological development, as well as the difficulties of negotiating increasingly complex regulatory and commercial environments that overlap the research domain. Further, numerous barriers to translational science have emerged among the nation's academic research centers, including basic structural and cultural impediments to innovation and collaboration, shortages of trained investigators, and inadequate funding.To address these serious and systemic problems, in 2006 the National Institutes of Health created the Clinical and Translational Science Awards (CTSA) program, which aims to catalyze the transformation of biomedical research at a national level, speeding the discovery and development of therapies, fostering collaboration, engaging communities, and training succeeding generations of clinical and translational researchers. The authors report in detail on the planning process, begun in 2008, that was used to engage stakeholders and to identify, refine, and ultimately implement the CTSA program's overarching strategic goals. They also discuss the implications and likely impact of this strategic planning process as it is applied among the nation's academic health centers.

The material, moral, and affective worlds of dealing and crime among young men entrenched in an inner city drug scene

PubMed Central

Fast, Danya; Shoveller, Jean; Kerr, Thomas

2017-01-01

A large body of previous research has elucidated how involvement in drug dealing and crime among marginalized urban youth who use drugs is shaped by the imperatives of addiction and survival in the context of poverty. However, a growing body of research has examined how youth’s involvement in these activities is shaped by more expansive desires and moralities. In this paper, we examine the material, moral, and affective worlds of loosely gang affiliated, street level dealing and crime among one group of young men in Vancouver, Canada. Drawing on longitudinal interviews with 44 young men from 2008 to 2016, and ethnographic fieldwork with a group of approximately 15 of those young men over the same time period, we argue that for these youth, dealing and crime were not solely about economic survival, or even the accrual of highly meaningful forms of “street capital” in the margins. Rather, as “regimes of living,” dealing and crime also opened up new value systems, moral logics, and affects in relation to the tremendous risks, potential rewards, and crushing boredom of life in the margins. These activities were also understood as a way into deeply desired forms of social spatial belonging in the city, which had previously only been imagined. However, across time dealing and crime ultimately “embedded” young men in cycles of incarceration, destitution, addictions, and mental health crises that ultimately reinforced their exclusion – from legal employment, but also within the world of crime. The findings of this study underscore the importance of adopting a life course perspective in order to meaningfully address the harms associated with involvement in dealing and crime among youth in our setting. PMID:28343062

Genes and chronic obstructive pulmonary disease.

PubMed

Foreman, Marilyn G; Campos, Michael; Celedón, Juan C

2012-07-01

Although much remains to be done, recent advances and the advent of new methodologies are promising and should yield increased understanding of the genetic and epigenetic mechanisms influencing the pathogenesis of COPD, both related and unrelated to severe AAT deficiency. Such understanding should ultimately be translated into novel approaches to prevent, diagnose, and treat COPD. Copyright © 2012 Elsevier Inc. All rights reserved.

Patterns of knowing: proposing a theory for nursing leadership.

PubMed

Jackson, Janet R; Clements, Paul T; Averill, Jennifer B; Zimbro, Kathie

2009-01-01

In a time of chaotic and unpredictable health care, it is vital for nursing to employ a nursing leadership theory that is specifically applicable to nurses and will holistically, and comprehensively address and support both the science and art of this honored profession. The authors propose that Nursing Leadership Knowing can address and impact the myriad issues confronting managers and administrators within the turbulent health care industry, with the ultimate goals of quality comprehensive patient care and improved employee satisfaction. They believe that Nursing Leadership Knowing, grounded in the realties of nursing experience, is a logical theoretical extension that can be translated into nursing leadership practice particular and specific focus on empirics and evidence-based practice will not attend to the robust and multidimensional underpinnings of the lived experience that is so vital to nursing as a caring profession. The ideal of nursing leadership theory is not a single-focused shadow of its history, but a rich, inclusive, multi-faceted network of knowing. As such, Nursing Leadership Knowing provides a forum for leaders to enhance their practice, as well as their relationship with their employees, which ultimately translates into optimal care for the patients we serve.

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

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan

Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.« less

Paleogeographic constraints on continental-scale source-to-sink systems: Northern South America and its Atlantic margins

NASA Astrophysics Data System (ADS)

Bajolet, Flora; Chardon, Dominique; Rouby, Delphine; Dall'Asta, Massimo; Roig, Jean-Yves; Loparev, Artiom; Coueffe, Renaud

2017-04-01

Our work aims at setting the evolving boundary conditions of erosion and sediments transfer, transit, and onshore-offshore accumulations on northern South America and along its Atlantic margins. Since the Early Mesozoic, the source-to-sink system evolved under the interplay of four main processes, which are (i) volcanism and arc building along the proto-Andes, (ii) long-term dynamics of the Amazon incratonic basin, (iii) rifting, relaxation and rejuvenation of the Atlantic margins and (iv) building of the Andes. We compiled information available from geological maps and the literature regarding tectonics, plate kinematics, magmatism, stratigraphy, sedimentology (including paleoenvironments and currents) and thermochronology to produce a series of paleogeographic maps showing the tectonic and kinematic framework of continental areas under erosion (sources), by-pass and accumulation (sinks) over the Amazonian craton, its adjacent regions and along its Atlantic margins. The maps also allow assessing the relative impact of (i) ongoing Pacific subduction, (ii) Atlantic rifting and its aftermath, and (iii) Atlantic slab retreat from under the Caribbean domain on the distribution and activity of onshore/offshore sedimentary basins. Stratigraphic and thermochronology data are also used to assess denudation / vertical motions due to sediment transfers and lithosphere-asthenosphere interactions. This study ultimately aims at linking the sediment routing system to long-wavelength deformation of northern South America under the influence of mountain building, intracratonic geodynamics, divergent margin systems and mantle dynamics.

Two Basic Scientists Walk into a Translational Space.

PubMed

2017-09-21

When John Schiller first joined Douglas Lowy's lab at the National Cancer Institute of the NIH, he could have not predicted that their common interest in the molecular biology of oncogenes would set them in path for discoveries that ultimately enabled the development of a vaccine for the human papillomavirus, which causes the majority of cervical cancers worldwide. John and Doug, the recipients of the 2017 Lasker-DeBakey Clinical Award, have joined Cell editor João Monteiro in a Conversation about science, public health, and the joys and challenges of being basic scientists in a translational space. Annotated excerpts from this conversation are presented below. Copyright © 2017. Published by Elsevier Inc.

Long-Range Pre-Thermal Time Crystals

NASA Astrophysics Data System (ADS)

Machado, Francisco; Else, Dominic V.; Nayak, Chetan; Yao, Norman

Driven quantum systems have recently enabled the realization of a discrete time crystal - an intrinsically out-of-equilibrium phase of matter that spontaneously breaks time translation symmetry. One strategy to prevent the drive-induced, runaway heating of the time crystal phase is the presence of strong disorder leading to many-body localization. A simpler disorder-less approach is to work in the pre-thermal regime where time crystalline order can persist to long times, before ultimately being destroyed by thermalization. In this talk, we will consider the interplay between long-range interactions, dimensionality, and pre-thermal time-translation symmetry breaking. As an example, we will consider the phase diagram of a 1D long-range pre-thermal time crystal.

Tri-modal confocal margin screening for the presence of residual squamous cell carcinoma in Mohs surgical excisions

NASA Astrophysics Data System (ADS)

Bar, Anna; Snavely, Nicholas; Chen, Nathaniel; Jacques, Steven; Gareau, Daniel S.

2012-03-01

Screening cancer in excision margins may be done with confocal microscopy to save time and cost over the gold standard histopathology (H&E). However, diagnostic accuracy requires sufficient contrast. Reflectance mode enables detection of large (>500um) nodular tumors. Enhanced nuclear contrast with acridine orange fluorescence mode additionally enables detection of tiny (<50um) basal cell carcinomas. Here, we present a novel combination of three modes to detect squamous cell carcinoma (SCC). Accurate screening of SCC requires eosin fluorescence, reflectance and acridine orange fluorescence to enable contrast for cytoplasm, collagen and nuclei respectively. Combining these signals replicates H&E for rapid clinical translation.

Parotid gland biopsy and /sup 67/Ga imaging correlation in systemic sarcoidosis

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

Brantley, S.D.; Orzel, J.A.; Weiland, F.L.

1987-03-01

We correlated the results of parotid gland biopsy, chest roentgenograms, and gallium citrate scintigraphy in 24 patients evaluated for possible systemic sarcoidosis. Of 19 patients ultimately proven to have sarcoidosis, 11 (57.9 percent) had positive parotid gland biopsy. The yield of parotid gland biopsy in patients with abnormal gallium parotid activity was only marginally higher (64.7 percent). Abnormal parotid gland uptake of gallium citrate was seen in 17 of these 19 patients (89.5 percent) and was always associated with abnormal lung or perihilar activity. The parotid gland biopsy is a useful technique for obtaining the tissue diagnosis of sarcoidosis; however,more » gallium scintigraphy should not be performed to select patients as this will only marginally increase the biopsy yield.« less

Advancing neurosurgery through translational research.

PubMed

Lacey, Claire; Sutherland, Garnette

2013-01-01

Every year, the number of published research articles increases significantly. However, many potentially useful ideas are lost in this flood of data. Translational research provides a framework through which investigators or laboratories can maximize the likelihood that the product of their research will be adopted in medical practice. There are 2 recognizable models of translation appropriate for the majority of research: investigator driven and industry enabled. Investigator-driven research has more range because it does not have to consider the profit margin of research, but it is a slow process. The industry-enabled model accelerates the translational research process through the power of industry funding but is interested primarily in products with potential for profit. Two cases are examined to illustrate different methods of partnering with industry. IMRIS is a company founded by investigators to distribute intraoperative magnetic resonance imaging technology based on a movable high-field magnet. It took 7 years for IMRIS to make its first sale, but it is now a successful company. With neuroArm, a surgical robot, investigators decided to sell the intellectual property to an established company to ensure successful global commercialization. Translational research advances medicine by creating and distributing effective solutions to contemporary problems.

Effects of Different PER Translational Kinetics on the Dynamics of a Core Circadian Clock Model

PubMed Central

Nieto, Paula S.; Revelli, Jorge A.; Garbarino-Pico, Eduardo; Condat, Carlos A.; Guido, Mario E.; Tamarit, Francisco A.

2015-01-01

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis. PMID:25607544

Effects of different per translational kinetics on the dynamics of a core circadian clock model.

PubMed

Nieto, Paula S; Revelli, Jorge A; Garbarino-Pico, Eduardo; Condat, Carlos A; Guido, Mario E; Tamarit, Francisco A

2015-01-01

Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.

MRI Quantification of Human Spine Cartilage Endplate Geometry: Comparison With Age, Degeneration, Level, and Disc Geometry

PubMed Central

DeLucca, John F.; Peloquin, John M.; Smith, Lachlan J.; Wright, Alexander C.; Vresilovic, Edward J.; Elliott, Dawn M.

2017-01-01

Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3–1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. PMID:27232974

The influence of FRCs reinforcement on marginal adaptation of CAD/CAM composite resin endocrowns after simulated fatigue loading.

PubMed

Rocca, Giovanni Tommaso; Saratti, Carlo Massimo; Poncet, Antoine; Feilzer, Albert J; Krejci, Ivo

2016-05-01

To evaluate the marginal adaptation of endodontically treated molars restored with CAD/CAM composite resin endocrowns either with or without reinforcement by fibre reinforced composites (FRCs), used in different configurations. 32 human endodontically treated molars were cut 2 mm over the CEJ. Two interproximal boxes were created with the margins located 1 mm below the CEJ (distal box) and 1 mm over the CEJ (mesial box). All specimens were divided in four groups (n = 8). The pulp chamber was filled with: group 1 (control), hybrid resin composite (G-aenial Posterior, GC); group 2, as group 1 but covered by 3 meshes of E-glass fibres (EverStick NET, Stick Tech); group 3, FRC resin (EverX Posterior, GC); group 4, as group 3 but covered by 3 meshes of E-glass fibres. The crowns of all teeth were restored with CAD/CAM composite resin endocrowns (LAVA Ultimate, 3M). All specimens were thermo-mechanically loaded in a computer-controlled chewing machine (600,000 cycles, 1.6 Hz, 49 N and simultaneously 1500 thermo-cycles, 60 s, 5-55 °C). Marginal analysis before and after the loading was carried out on epoxy replicas by SEM at 200× magnification. For all the groups, the percentage values of perfect marginal adaptation after loading were always significantly lower than before loading (p < 0.05). The marginal adaptation before and after loading was not significantly different between the experimental groups (p > 0.05). Within the limitations of this in vitro study, the use of FRCs to reinforce the pulp chamber of devitalized molars restored with CAD/CAM composite resin restorations did not significantly influenced their marginal quality.

Across Europe to CERN: Taking Students on the Ultimate Physics Experience

ERIC Educational Resources Information Center

Wheeler, Sam

2018-01-01

In 2013, I was an Einstein Fellow with the U.S. Department of Energy and I was asked by a colleague, working in a senator's office, if I would join him in a meeting with a physicist to "translate" the science into something more understandable. That meeting turned out to be a wonderful opportunity I would never have otherwise had. During…

Ontogenetical and histochemical studies on the translator apparatus in Calotropis procera R. Br. I. The retinaculum.

PubMed

Vijayaraghavan, M R; Cheema, K

1977-01-01

Translator apparatus consists of 2 parts--the corpusculum, which is attached to the margin of the stigmatic head between the anthers, and a pair of arms by which the corpusculum is attached to the pollinia of the adjacent anther halves. Retinaculum spans the lateral blade of the corpusculum to the acellular beak of the pollinium. Ontogenetically, it is the secretory product of the stigma along the secondary stigmatic groove. Histochemically, it is composed of lipid, lignin, cutin and a little amount of proteins. Retinaculum, like corpusculum, is stigmatic in origin, but differs histochemically from the latter being composed mainly of lipo-protein complex and lacking phenolic compounds.

Development, survival, and phenotypic plasticity in anthropogenic landscapes: trade-offs between offspring quantity and quality in the nettle-feeding peacock butterfly.

PubMed

Serruys, Mélanie; Van Dyck, Hans

2014-10-01

Habitats selected for development may have important fitness consequences. This is relevant within the framework of niche shifts in human-dominated landscapes. Currently, the peacock butterfly (Aglais io) occurs ubiquitously, covering many habitat types, whereas its distribution used to be much more restricted. Indeed, its host plant (stinging nettle Urtica dioica) was limited to natural forest gaps on relatively nitrogen-rich soil, but due to land use changes and eutrophication, host plants are now quasi-omnipresent in Western Europe. In order to assess the impact of specific anthropogenic habitat types on host plant quality and environmental conditions for phenotypic trait values, an experiment was conducted in woodlands, field margins, and urban gardens. Larval development was studied in field enclosures, and adult traits were analyzed to test predicted effects of warmer and more nitrogen-rich conditions in field margins compared to woodlands and urban gardens. Survival to the adult stage was highest in woodlands and lowest in field margins, and whilst development time did not differ amongst habitat types, butterflies that developed in field margins were larger and had higher lipid content and wing loadings than conspecifics from woodlands and urban gardens. Nettles in field margins provided warmer microclimates. However, and contrary to predictions, the nitrogen level within host plant leaves was highest in woodlands. Hence, anthropogenic landscapes may pose a conflict for choosing what is ultimately the best breeding habitat, as survival was highest in woodlands (followed by urban gardens), but adults with highest fitness predictions were produced in field margins (and secondarily urban gardens).

TaxaGloss - A Glossary and Translation Tool for Biodiversity Studies.

PubMed

Collin, Rachel; Fredericq, Suzanne; Freshwater, D Wilson; Gilbert, Edward; Madrid, Maycol; Maslakova, Svetlana; Miglietta, Maria Pia; Rocha, Rosana M; Rodríguez, Estefanía; Thacker, Robert W

2016-01-01

Correctly identifying organisms is key to most biological research, and is especially critical in areas of biodiversity and conservation. Yet it remains one of the greatest challenges when studying all but the few well-established model systems. The challenge is in part due to the fact that most species have yet to be described, vanishing taxonomic expertise and the relative inaccessibility of taxonomic information. Furthermore, identification keys and other taxonomic resources are based on complex, taxon-specific vocabularies used to describe important morphological characters. Using these resources is made difficult by the fact that taxonomic documentation of the world's biodiversity is an international endeavour, and keys and field guides are not always available in the practitioner's native language. To address this challenge, we have developed a publicly available on-line illustrated multilingual glossary and translation tool for technical taxonomic terms using the Symbiota Software Project biodiversity platform. Illustrations, photographs and translations have been sourced from the global community of taxonomists working with marine invertebrates and seaweeds. These can be used as single-language illustrated glossaries or to make customized translation tables. The glossary has been launched with terms and illustrations of seaweeds, tunicates, sponges, hydrozoans, sea anemones, and nemerteans, and already includes translations into seven languages for some groups. Additional translations and development of terms for more taxa are underway, but the ultimate utility of this tool depends on active participation of the international taxonomic community.

Increasing Safety of a Robotic System for Inner Ear Surgery Using Probabilistic Error Modeling Near Vital Anatomy

PubMed Central

Dillon, Neal P.; Siebold, Michael A.; Mitchell, Jason E.; Blachon, Gregoire S.; Balachandran, Ramya; Fitzpatrick, J. Michael; Webster, Robert J.

2017-01-01

Safe and effective planning for robotic surgery that involves cutting or ablation of tissue must consider all potential sources of error when determining how close the tool may come to vital anatomy. A pre-operative plan that does not adequately consider potential deviations from ideal system behavior may lead to patient injury. Conversely, a plan that is overly conservative may result in ineffective or incomplete performance of the task. Thus, enforcing simple, uniform-thickness safety margins around vital anatomy is insufficient in the presence of spatially varying, anisotropic error. Prior work has used registration error to determine a variable-thickness safety margin around vital structures that must be approached during mastoidectomy but ultimately preserved. In this paper, these methods are extended to incorporate image distortion and physical robot errors, including kinematic errors and deflections of the robot. These additional sources of error are discussed and stochastic models for a bone-attached robot for otologic surgery are developed. An algorithm for generating appropriate safety margins based on a desired probability of preserving the underlying anatomical structure is presented. Simulations are performed on a CT scan of a cadaver head and safety margins are calculated around several critical structures for planning of a robotic mastoidectomy. PMID:29200595

Increasing safety of a robotic system for inner ear surgery using probabilistic error modeling near vital anatomy

NASA Astrophysics Data System (ADS)

Dillon, Neal P.; Siebold, Michael A.; Mitchell, Jason E.; Blachon, Gregoire S.; Balachandran, Ramya; Fitzpatrick, J. Michael; Webster, Robert J.

2016-03-01

Safe and effective planning for robotic surgery that involves cutting or ablation of tissue must consider all potential sources of error when determining how close the tool may come to vital anatomy. A pre-operative plan that does not adequately consider potential deviations from ideal system behavior may lead to patient injury. Conversely, a plan that is overly conservative may result in ineffective or incomplete performance of the task. Thus, enforcing simple, uniform-thickness safety margins around vital anatomy is insufficient in the presence of spatially varying, anisotropic error. Prior work has used registration error to determine a variable-thickness safety margin around vital structures that must be approached during mastoidectomy but ultimately preserved. In this paper, these methods are extended to incorporate image distortion and physical robot errors, including kinematic errors and deflections of the robot. These additional sources of error are discussed and stochastic models for a bone-attached robot for otologic surgery are developed. An algorithm for generating appropriate safety margins based on a desired probability of preserving the underlying anatomical structure is presented. Simulations are performed on a CT scan of a cadaver head and safety margins are calculated around several critical structures for planning of a robotic mastoidectomy.

How Cuba's Latin American School of Medicine challenges the ethics of physician migration.

PubMed

Huish, Robert

2009-08-01

This paper demonstrates a working alternative to the accepted ethics of physician migration. A dominant cosmopolitan ethics encourages upward mobility of physicians in a globalized labour force, and this ultimately advances the position of individuals rather than improving public health-care service for vulnerable communities in the global South. Cuba's Escuela Latinoamericana de Medicina (ELAM) challenges this trend as its institutional ethics furnishes graduates with appropriate skills, knowledge and service ethics to deliver quality care in marginalized areas. This paper provides an analysis of how ELAM trains physicians in community-oriented service for marginalized areas in the global South. The principle finding of this analysis is that ELAM exhibits a working alternative to the accepted ethics of physician migration, as it encourages graduates to practice in marginalized communities rather than feed the migration pipeline into the North. Arguably, ELAM serves as an important case study in how a medical school's ethics can work to bring graduates closer to the communities that are in desperate need of their skills and of their compassion.

Can we prevent ischemic-type biliary lesions in donation after circulatory determination of death liver transplantation?

PubMed

Hessheimer, Amelia J; Cárdenas, Andrés; García-Valdecasas, Juan C; Fondevila, Constantino

2016-07-01

The pool of livers for transplantation consists of an increasingly greater proportion of marginal grafts, in particular those arising through donation after circulatory determination of death (DCD). However, a primary factor limiting the use of marginal livers, and, thereby, the applicability of liver transplantation in general, is concern over the subsequent development of ischemic-type biliary lesion (ITBL). ITBL is a devastating complication of liver transplantation; in its most severe forms, recipients suffer frequent infectious complications that require repeated invasive biliary procedures and ultimately result in either retransplantation or death. In the present review article, we discuss our current understanding of ITBL pathogenesis as it pertains to DCD, in particular. We discuss the most relevant theories regarding its development and provide a comprehensive overview of the most promising strategies we have available today to prevent the appearance of ITBL, strategies that may, furthermore, allow us to transplant a greater proportion of marginal livers in the future. Liver Transplantation 22 1025-1033 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.

PubMed

Pelletier, Jerry; Graff, Jeremy; Ruggero, Davide; Sonenberg, Nahum

2015-01-15

Elevated protein synthesis is an important feature of many cancer cells and often arises as a consequence of increased signaling flux channeled to eukaryotic initiation factor 4F (eIF4F), the key regulator of the mRNA-ribosome recruitment phase of translation initiation. In many cellular and preclinical models of cancer, eIF4F deregulation results in changes in translational efficiency of specific mRNA classes. Importantly, many of these mRNAs code for proteins that potently regulate critical cellular processes, such as cell growth and proliferation, enhanced cell survival and cell migration that ultimately impinge on several hallmarks of cancer, including increased angiogenesis, deregulated growth control, enhanced cellular survival, epithelial-to-mesenchymal transition, invasion, and metastasis. By being positioned as the molecular nexus downstream of key oncogenic signaling pathways (e.g., Ras, PI3K/AKT/TOR, and MYC), eIF4F serves as a direct link between important steps in cancer development and translation initiation. Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eIF4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents. ©2014 American Association for Cancer Research.

Companion animals: Translational scientist’s new best friends

PubMed Central

Kol, Amir; Arzi, Boaz; Athanasiou, Kyriacos A.; Farmer, Diana L.; Nolta, Jan A.; Rebhun, Robert B.; Chen, Xinbin; Griffiths, Leigh G.; Verstraete, Frank J. M.; Murphy, Christopher J.; Borjesson, Dori L.

2016-01-01

Knowledge and resources derived from veterinary medicine represent an underused resource that could serve as a bridge between data obtained from diseases models in laboratory animals and human clinical trials. Naturally occurring disease in companion animals that display the defining attributes of similar, if not identical, diseases in humans hold promise for providing predictive proof of concept in the evaluation of new therapeutics and devices. Here we outline comparative aspects of naturally occurring diseases in companion animals and discuss their current uses in translational medicine, benefits, and shortcomings. Last, we envision how these natural models of disease might ultimately decrease the failure rate in human clinical trials and accelerate the delivery of effective treatments to the human clinical market. PMID:26446953

The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.

PubMed

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2011-02-01

To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma. Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed. A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival. The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found. The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.

Evaluation of marginal and internal adaptation of hybrid and nanoceramic systems with microcomputed tomography: An in vitro study.

PubMed

Yildirim, Güler; Uzun, Ismail H; Keles, Ali

2017-08-01

The accuracy of recently introduced chairside computer-aided design and computer-aided manufacturing (CAD-CAM) blocks is not well established, and marginal integrity and internal adaptation are not known. The purpose of this in vitro study was to evaluate the marginal and internal adaptation of hybrid and nanoceramics using microcomputed tomography (μ-CT). The marginal and internal adaptation of 3 polymer-infiltrated ceramic-network (PICN) materials (Vita Enamic [VE]; Lava Ultimate [LU]; Vita Suprinity [VS]) were compared with lithium disilicate (IPS e.max.CAD, IPS). Ninety-six specimens (48 dies and 48 crowns) were prepared (n=12 each group) using a chairside CAD-CAM system. The restorations were scanned with μ-CT, with 160 measurements made for each crown, and used in 2-dimensional (2D) analysis. The marginal adaptation of marginal discrepancy (MD), absolute marginal discrepancy (AMD), internal adaptation of shoulder area (SA), axial space (AS), and occlusal space (OS) were compared using appropriate statistical analysis methods (α=.05). Cement volumes were compared using 3D analysis. The IPS blocks showed higher MD (130 μm), AMD (156 μm), SA (111 μm) (P<.05), AS (52 μm), and OS (192 μm) than the other blocks (P<.01). The adaptation values of VS were significantly lower than those of the IPS block (P<.05). The adaption values of the LU and VE blocks were significantly lower than those of others (P<.01) but were statistically similar to one another (P>.05). IPS had the largest cement space at 18 mm 3 (P<.01). The marginal and internal adaptation values were within a clinically acceptable range for all 3 hybrids and nanoceramics tested. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Bilingual and Monolingual Idiom Processing Is Cut from the Same Cloth: The Role of the L1 in Literal and Figurative Meaning Activation

PubMed Central

Beck, Sara D.; Weber, Andrea

2016-01-01

The present study examines non-native (L2) and native (L1) listeners' access to figurative idiomatic meaning and literal constituent meaning in two cross-modal priming experiments. Proficient German learners of English (L2) and native speakers of American English (L1) responded to English target words preceded by English idioms embedded in non-biasing prime sentences in a lexical decision task. English idioms differed in levels of translatability: Lexical level idioms had word-for-word translation equivalents in German, while post-lexical level idioms had matching idiomatic concepts in German but could not be translated word for word. Target words either related to the figurative meaning of the idiom or related to the literal meaning of the final constituent word of the idiom (e.g., to pull someone's leg, literal target: walk, figurative target: joke). Both L1 and L2 listeners showed facilitatory priming for literally- and figuratively-related target words compared to unrelated control target words, with only marginal differences between the listener groups. No effect of translatability was found; that is, the existence of word-for-word translation equivalents in German neither facilitated nor hindered meaning activation for German L2 listeners. The results are interpreted in the context of L1 and L2 models of idiom processing as well as further relevant translation studies. PMID:27667979

Bilingual and Monolingual Idiom Processing Is Cut from the Same Cloth: The Role of the L1 in Literal and Figurative Meaning Activation.

PubMed

Beck, Sara D; Weber, Andrea

2016-01-01

The present study examines non-native (L2) and native (L1) listeners' access to figurative idiomatic meaning and literal constituent meaning in two cross-modal priming experiments. Proficient German learners of English (L2) and native speakers of American English (L1) responded to English target words preceded by English idioms embedded in non-biasing prime sentences in a lexical decision task. English idioms differed in levels of translatability: Lexical level idioms had word-for-word translation equivalents in German, while post-lexical level idioms had matching idiomatic concepts in German but could not be translated word for word. Target words either related to the figurative meaning of the idiom or related to the literal meaning of the final constituent word of the idiom (e.g., to pull someone's leg, literal target: walk, figurative target: joke). Both L1 and L2 listeners showed facilitatory priming for literally- and figuratively-related target words compared to unrelated control target words, with only marginal differences between the listener groups. No effect of translatability was found; that is, the existence of word-for-word translation equivalents in German neither facilitated nor hindered meaning activation for German L2 listeners. The results are interpreted in the context of L1 and L2 models of idiom processing as well as further relevant translation studies.

Marginal and internal fit of nano-composite CAD/CAM restorations.

PubMed

Park, So-Hyun; Yoo, Yeon-Jee; Shin, Yoo-Jin; Cho, Byeong-Hoon; Baek, Seung-Ho

2016-02-01

The purpose of this study was to compare the marginal and internal fit of nano-composite CAD-CAM restorations. A full veneer crown and an mesio-occluso-distal (MOD) inlay cavity, which were prepared on extracted human molars, were used as templates of epoxy resin replicas. The prepared teeth were scanned and CAD-CAM restorations were milled using Lava Ultimate (LU) and experimental nano-composite CAD/CAM blocks (EB) under the same milling parameters. To assess the marginal and internal fit, the restorations were cemented to replicas and were embedded in an acrylic mold for sectioning at 0.5 mm intervals. The measured gap data were pooled according to the block types and measuring points for statistical analysis. Both the block type and measuring point significantly affected gap values, and their interaction was significant (p = 0.000). In crowns and inlays made from the two blocks, gap values were significantly larger in the occlusal area than in the axial area, while gap values in the marginal area were smallest (p < 0.001). Among the blocks, the restorations milled from EB had a significantly larger gap at all measuring points than those milled from LU (p = 0.000). The marginal and internal gaps of the two nano-composite CAD/CAM blocks differed according to the measuring points. Among the internal area of the two nano-composite CAD/CAM restorations, occlusal gap data were significantly larger than axial gap data. The EB crowns and inlays had significantly larger gaps than LU restorations.

Conversion of laser energy to gas kinetic energy

NASA Technical Reports Server (NTRS)

Caledonia, G. E.

1976-01-01

Techniques for the gas phase absorption of laser radiation for ultimate conversion to gas kinetic energy are discussed. Particular emphasis is placed on absorption by the vibration rotation bands of diatomic molecules at high pressures. This high pressure absorption appears to offer efficient conversion of laser energy to gas translational energy. Bleaching and chemical effects are minimized and the variation of the total absorption coefficient with temperature is minimal.

Design Through Manufacturing: The Solid Model - Finite Element Analysis Interface

NASA Technical Reports Server (NTRS)

Rubin, Carol

2003-01-01

State-of-the-art computer aided design (CAD) presently affords engineers the opportunity to create solid models of machine parts which reflect every detail of the finished product. Ideally, these models should fulfill two very important functions: (1) they must provide numerical control information for automated manufacturing of precision parts, and (2) they must enable analysts to easily evaluate the stress levels (using finite element analysis - FEA) for all structurally significant parts used in space missions. Today's state-of-the-art CAD programs perform function (1) very well, providing an excellent model for precision manufacturing. But they do not provide a straightforward and simple means of automating the translation from CAD to FEA models, especially for aircraft-type structures. The research performed during the fellowship period investigated the transition process from the solid CAD model to the FEA stress analysis model with the final goal of creating an automatic interface between the two. During the period of the fellowship a detailed multi-year program for the development of such an interface was created. The ultimate goal of this program will be the development of a fully parameterized automatic ProE/FEA translator for parts and assemblies, with the incorporation of data base management into the solution, and ultimately including computational fluid dynamics and thermal modeling in the interface.

Marginal adaptation of CAD-CAM onlays: Influence of preparation design and impression technique.

PubMed

Lima, Fernanda Ferruzzi; Neto, Constantino Fernandes; Rubo, José H; Santos, Gildo Coelho; Moraes Coelho Santos, Maria Jacinta

2018-03-15

Factors that may affect the marginal adaptation of computer-aided design and computer-aided manufacturing (CAD-CAM) restorations include preparation design, impression technique, and CAD-CAM system. The influence of impression technique and preparation design on CAD-CAM partial coverage restorations has not been fully addressed. The purpose of this in vitro study was to investigate the influence of direct and indirect digital impression techniques and 2 preparation designs on the marginal adaptation of CAD-CAM onlays. Two mesio-occlusal buccal onlay preparations with reduction of the mesiobuccal cusp were made: conventional preparation (CP) with a 1.2-mm modified shoulder margin and modified preparation (MP) flat cuspal reduction without shoulder. Virtual models were generated from each preparation by using a digital scanner (BlueCam; Dentsply Sirona) from the plastic teeth (direct digital impression) or from the stone dies (indirect digital impression). Onlays were designed using a CAD-CAM system (CEREC 4.0; Dentsply Sirona), and nanoceramic resin blocks (Lava Ultimate Restorative; 3M ESPE) were milled using the CEREC MCX milling machine. Marginal discrepancy was evaluated using an optical stereomicroscope at ×25 magnification in 18 locations distributed along the margins of the preparation. The data were analyzed by using 3-way ANOVA followed by the Tukey HSD test (α=.05). CP presented a statistically significant reduced average marginal adaptation (59 ±50 μm) than did MP (69 ±58 μm) (P<.001). The Tukey HSD test showed the presence of a significantly larger marginal discrepancy in the mesial and buccal locations of MP when compared with CP. Regarding impression techniques, the buccal location presented the smallest average marginal discrepancy in restorations fabricated with indirect impression when compared with direct impression (42 ±33 μm and 60 ±39 μm) (P<.001). The results showed that conventional preparation with a modified shoulder margin presented improved marginal adaptation compared with modified preparation with flat cuspal reduction. Direct and indirect digital impression techniques produced restorations within a clinically acceptable range; however, the indirect impression technique resulted in the fabrication of restorations with superior marginal adaptation on the buccal location. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

"This is Why you've Been Suffering": Reflections of Providers on Neuroimaging in Mental Health Care.

PubMed

Borgelt, Emily; Buchman, Daniel Z; Illes, Judy

2011-03-01

Mental health care providers increasingly confront challenges posed by the introduction of new neurotechnology into the clinic, but little is known about the impact of such capabilities on practice patterns and relationships with patients. To address this important gap, we sought providers' perspectives on the potential clinical translation of functional neuroimaging for prediction and diagnosis of mental illness. We conducted 32 semi-structured telephone interviews with mental health care providers representing psychiatry, psychology, family medicine, and allied mental health. Our results suggest that mental health providers have begun to re-conceptualize mental illness with a neuroscience gaze. They report an epistemic commitment to the value of a brain scan to provide a meaningful explanation of mental illness for their clients. If functional neuroimaging continues along its projected trajectory to translation, providers will ultimately have to negotiate its role in mental health. Their perspectives, therefore, enrich bioethical discourse surrounding neurotechnology and inform the translational pathway.

FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

DOE PAGES

Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan; ...

2016-09-13

Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. But, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. We found that this slowdown wasmore » most prominent for translation-related and mitochondrial proteins. Conversely, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.« less

Resuscitation Education Science: Educational Strategies to Improve Outcomes From Cardiac Arrest: A Scientific Statement From the American Heart Association.

PubMed

Cheng, Adam; Nadkarni, Vinay M; Mancini, Mary Beth; Hunt, Elizabeth A; Sinz, Elizabeth H; Merchant, Raina M; Donoghue, Aaron; Duff, Jonathan P; Eppich, Walter; Auerbach, Marc; Bigham, Blair L; Blewer, Audrey L; Chan, Paul S; Bhanji, Farhan

2018-06-21

The formula for survival in resuscitation describes educational efficiency and local implementation as key determinants in survival after cardiac arrest. Current educational offerings in the form of standardized online and face-to-face courses are falling short, with providers demonstrating a decay of skills over time. This translates to suboptimal clinical care and poor survival outcomes from cardiac arrest. In many institutions, guidelines taught in courses are not thoughtfully implemented in the clinical environment. A current synthesis of the evidence supporting best educational and knowledge translation strategies in resuscitation is lacking. In this American Heart Association scientific statement, we provide a review of the literature describing key elements of educational efficiency and local implementation, including mastery learning and deliberate practice, spaced practice, contextual learning, feedback and debriefing, assessment, innovative educational strategies, faculty development, and knowledge translation and implementation. For each topic, we provide suggestions for improving provider performance that may ultimately optimize patient outcomes from cardiac arrest. © 2018 American Heart Association, Inc.

Genetics and epigenetics of rheumatoid arthritis

PubMed Central

Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

2013-01-01

Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

Translating findings from basic fear research to clinical psychiatry in Puerto Rico

PubMed Central

Quirk, Gregory J.; Martinez, Karen G.; Nazario Rodríguez, Lelis L.

2009-01-01

Recent advances in the neuroscience of classical fear conditioning from both rodent and human studies are beginning to be translated to the psychiatry clinic. In particular, our understanding of fear extinction as a form of “safety learning” holds promise for the treatment of anxiety disorders in which extinction learning is thought to be compromised. The Department of Psychiatry at the UPR, School of Medicine promotes the development of innovative strategies for treating mental health problems. Given the burden resulting from anxiety disorders in Puerto Rico, and the lack of evidence-based treatment practices, there is a pressing need for a future center specializing in the treatment of anxiety related disorders. This center would also serve research and training functions, with the ultimate goal of translating extinction research into clinical practice. This review presents the current developments in extinction research and its relationship to anxiety disorders and treatment. We also analyze the available literature on the epidemiology of anxiety disorders and the existing evidence-based treatments for these conditions. PMID:18246959

“This is Why you've Been Suffering”: Reflections of Providers on Neuroimaging in Mental Health Care

PubMed Central

Borgelt, Emily; Buchman, Daniel Z.; Illes, Judy

2011-01-01

Mental health care providers increasingly confront challenges posed by the introduction of new neurotechnology into the clinic, but little is known about the impact of such capabilities on practice patterns and relationships with patients. To address this important gap, we sought providers' perspectives on the potential clinical translation of functional neuroimaging for prediction and diagnosis of mental illness. We conducted 32 semi-structured telephone interviews with mental health care providers representing psychiatry, psychology, family medicine, and allied mental health. Our results suggest that mental health providers have begun to re-conceptualize mental illness with a neuroscience gaze. They report an epistemic commitment to the value of a brain scan to provide a meaningful explanation of mental illness for their clients. If functional neuroimaging continues along its projected trajectory to translation, providers will ultimately have to negotiate its role in mental health. Their perspectives, therefore, enrich bioethical discourse surrounding neurotechnology and inform the translational pathway. PMID:21572566

Two-Photon and Second Harmonic Microscopy in Clinical and Translational Cancer Research

PubMed Central

PERRY, SETH W.; BURKE, RYAN M.; BROWN, EDWARD B.

2012-01-01

Application of two-photon microscopy (TPM) to translational and clinical cancer research has burgeoned over the last several years, as several avenues of pre-clinical research have come to fruition. In this review, we focus on two forms of TPM—two-photon excitation fluorescence microscopy, and second harmonic generation microscopy—as they have been used for investigating cancer pathology in ex vivo and in vivo human tissue. We begin with discussion of two-photon theory and instrumentation particularly as applicable to cancer research, followed by an overview of some of the relevant cancer research literature in areas that include two-photon imaging of human tissue biopsies, human skin in vivo, and the rapidly developing technology of two-photon microendoscopy. We believe these and other evolving two-photon methodologies will continue to help translate cancer research from the bench to the bedside, and ultimately bring minimally invasive methods for cancer diagnosis and treatment to therapeutic reality. PMID:22258888

Robust adaptive relative position and attitude control for spacecraft autonomous proximity.

PubMed

Sun, Liang; Huo, Wei; Jiao, Zongxia

2016-07-01

This paper provides new results of the dynamical modeling and controller designing for autonomous close proximity phase during rendezvous and docking in the presence of kinematic couplings and model uncertainties. A globally defined relative motion mechanical model for close proximity operations is introduced firstly. Then, in spite of the kinematic couplings and thrust misalignment between relative rotation and relative translation, robust adaptive relative position and relative attitude controllers are designed successively. Finally, stability of the overall system is proved that the relative position and relative attitude are uniformly ultimately bounded, and the size of the ultimate bound can be regulated small enough by control system parameters. Performance of the controlled overall system is demonstrated via a representative numerical example. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Tactical STOL moment balance through innovative configuration technology

NASA Technical Reports Server (NTRS)

Eckard, G. J.; Sutton, R. C.; Poth, G. E.

1981-01-01

Innovative and conventional thrust vectoring moment balance mechanisms, as applied to advanced tactical fighters, are examined. The innovative mechanisms include thrust line translation, life line translation, and auxiliary power control; the conventional mechanisms under investigation are horizontal tails, canards, and variable sweep wings. These mechanisms are tested for their ability to provide negative static margins for landing approach or relocation of the vectored thrust line nearer the aircraft's center of gravity. The net pitching moment due to wing, flaps, and vectored thrust lift would then be small, making possible beneficial trim forces from small trimming devices. These innovative mechanisms are, however, possibly heavy and must be evaluated on their complexity, reliability, maintainability, and STOL capabilities. Several candidate fighter configurations are compared and evaluated.

Role of TAR RNA splicing in translational regulation of simian immunodeficiency virus from rhesus macaques.

PubMed Central

Viglianti, G A; Rubinstein, E P; Graves, K L

1992-01-01

The untranslated leader sequences of rhesus macaque simian immunodeficiency virus mRNAs form a stable secondary structure, TAR. This structure can be modified by RNA splicing. In this study, the role of TAR splicing in virus replication was investigated. The proportion of viral RNAs containing a spliced TAR structure is high early after infection and decreases at later times. Moreover, proviruses containing mutations which prevent TAR splicing are significantly delayed in replication. These mutant viruses require approximately 20 days to achieve half-maximal virus production, in contrast to wild-type viruses, which require approximately 8 days. We attribute this delay to the inefficient translation of unspliced-TAR-containing mRNAs. The molecular basis for this translational effect was examined in in vitro assays. We found that spliced-TAR-containing mRNAs were translated up to 8.5 times more efficiently than were similar mRNAs containing an unspliced TAR leader. Furthermore, these spliced-TAR-containing mRNAs were more efficiently associated with ribosomes. We postulate that the level of TAR splicing provides a balance for the optimal expression of both viral proteins and genomic RNA and therefore ultimately controls the production of infectious virions. Images PMID:1629957

Synaptic control of local translation: the plot thickens with new characters.

PubMed

Thomas, María Gabriela; Pascual, Malena Lucía; Maschi, Darío; Luchelli, Luciana; Boccaccio, Graciela Lidia

2014-06-01

The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

Symptoms of depression as reported by Norwegian adolescents on the Short Mood and Feelings Questionnaire

PubMed Central

Lundervold, Astri J.; Breivik, Kyrre; Posserud, Maj-Britt; Stormark, Kjell Morten; Hysing, Mari

2013-01-01

The present study investigated sex-differences in reports of depressive symptoms on a Norwegian translation of the short version of the Mood and Feelings Questionnaire (SMFQ). The sample comprised 9702 Norwegian adolescents (born 1993–1995, 54.9% girls), mainly attending highschool. A set of statistical analyses were run to investigate the dimensionality of the SMFQ. Girls scored significantly higher than boys on the SMFQ and used the most severe response-category far more frequently. Overall, the statistical analyses supported the essential unidimensionality of SMFQ. However, the items with the highest loadings according to the bifactor analysis, reflecting problems related to tiredness, restlessness and concentration difficulties, indicated that some of the symptoms may both be independent of and part of the symptomatology of depression. Measurement invariance analysis showed that girls scored slightly higher on some items when taking the latent variable into account; girls had a lower threshold for reporting mood problems and problems related to tiredness than boys, who showed a marginally lower threshold for reporting that no-one loved them. However, the effect on the total SMFQ score was marginal, supporting the use of the Norwegian translation of SMFQ as a continuous variable in further studies of adolescents. PMID:24062708

Understanding context in knowledge translation: a concept analysis study protocol.

PubMed

Squires, Janet E; Graham, Ian D; Hutchinson, Alison M; Linklater, Stefanie; Brehaut, Jamie C; Curran, Janet; Ivers, Noah; Lavis, John N; Michie, Susan; Sales, Anne E; Fiander, Michelle; Fenton, Shannon; Noseworthy, Thomas; Vine, Jocelyn; Grimshaw, Jeremy M

2015-05-01

To conduct a concept analysis of clinical practice contexts (work environments) that facilitate or militate against the uptake of research evidence by healthcare professionals in clinical practice. This will involve developing a clear definition of context by describing its features, domains and defining characteristics. The context where clinical care is delivered influences that care. While research shows that context is important to knowledge translation (implementation), we lack conceptual clarity on what is context, which contextual factors probably modify the effect of knowledge translation interventions (and hence should be considered when designing interventions) and which contextual factors themselves could be targeted as part of a knowledge translation intervention (context modification). Concept analysis. The Walker and Avant concept analysis method, comprised of eight systematic steps, will be used: (1) concept selection; (2) determination of aims; (3) identification of uses of context; (4) determination of defining attributes of context; (5) identification/construction of a model case of context; (6) identification/construction of additional cases of context; (7) identification/construction of antecedents and consequences of context; and (8) definition of empirical referents of context. This study is funded by the Canadian Institutes of Health Research (January 2014). This study will result in a much needed framework of context for knowledge translation, which identifies specific elements that, if assessed and used to tailor knowledge translation activities, will result in increased research use by nurses and other healthcare professionals in clinical practice, ultimately leading to better patient care. © 2014 John Wiley & Sons Ltd.

Poster — Thur Eve — 29: Characterization of Patient Immobilization for Head and Neck Cancer Treatment

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

Courneyea, L; Mullins, J; Howard, M

2014-08-15

Purpose: Evaluate an immobilization system to determine its adequacy for the reduced margins required for proton therapy. Methods: Twelve head-and-neck cancer patients were immobilized for conventional photon radiotherapy and imaged with pre- and post-treatment cone beam CTs (CBCTs) for each treatment fraction. To quantify the patient positioning reproducibility, each CBCT was registered to the simulation CT offline. Registrations were performed using auto-match tools and a matching volume-of-interest (VOI) consisting of a 5mm expansion around the mandible, occipital bone, C1/C2 and C7/T1. For each registration, the bony anatomy in the VOI was evaluated for agreement with the simulation position using 3more » and 5mm margins. Registrations were initially restricted to translational corrections. If the bony anatomy did not agree with the simulation position to within 3mm or 5mm, the auto-match was repeated with 3 additional rotational corrections. Intrafraction motion was calculated as the difference between the pre- and post-treatment CBCT matches. Results: Pre-treatment patient positioning agreed with the simulation CT to within 3mm/5mm for 62%/86% of fractions using translational matching and 84%/100% of fractions when rotations were included. Intrafraction motion averaged 1.1±0.8mm, with 12% of fractions having >2mm intrafraction motion. Post-treatment positioning accuracy was 57%/84% and 80%/100% for registrations without/with rotations. For the mandible, positioning accuracy dropped from 93% pre-treatment to 82% post-treatment. Conclusion: If rotational corrections are available, the immobilization system studied created reproducible patient positioning to within 3mm for 84% of fractions. However, intrafraction motion caused additional anatomy to fall outside the 3mm margin by the end of treatment.« less

The Emory Chemical Biology Discovery Center: leveraging academic innovation to advance novel targets through HTS and beyond.

PubMed

Johns, Margaret A; Meyerkord-Belton, Cheryl L; Du, Yuhong; Fu, Haian

2014-03-01

The Emory Chemical Biology Discovery Center (ECBDC) aims to accelerate high throughput biology and translation of biomedical research discoveries into therapeutic targets and future medicines by providing high throughput research platforms to scientific collaborators worldwide. ECBDC research is focused at the interface of chemistry and biology, seeking to fundamentally advance understanding of disease-related biology with its HTS/HCS platforms and chemical tools, ultimately supporting drug discovery. Established HTS/HCS capabilities, university setting, and expertise in diverse assay formats, including protein-protein interaction interrogation, have enabled the ECBDC to contribute to national chemical biology efforts, empower translational research, and serve as a training ground for young scientists. With these resources, the ECBDC is poised to leverage academic innovation to advance biology and therapeutic discovery.

A Journey in Science: Medical Scientist in Translation

PubMed Central

Hansson, Göran K

2014-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed and treated. In this volume, the Cerami Award Monograph is by Göran K Hansson, MD, PhD, Karolinska Institute. A visionary in the field of cardiovascular research, this is the story of Dr. Hansson’s scientific journey. PMID:25356751

The North Sakhalin Neogene total petroleum system of eastern Russia

USGS Publications Warehouse

Lindquist, S.J.

2000-01-01

The North Sakhalin Basin Province of eastern Russia contains one Total Petroleum System (TPS) ? North Sakhalin Neogene ? with more than 6 BBOE known, ultimately recoverable petroleum (61% gas, 36% oil, 3% condensate). Tertiary rocks in the basin were deposited by the prograding paleo-Amur River system. Marine to continental, Middle to Upper Miocene shale to coaly shale source rocks charged marine to continental Middle Miocene to Pliocene sandstone reservoir rocks in Late Miocene to Pliocene time. Fractured, self-sourced, Upper Oligocene to Lower Miocene siliceous shales also produce hydrocarbons. Geologic history is that of a Mesozoic Asian passive continental margin that was transformed into an active accretionary Tertiary margin and Cenozoic fold belt by the collision of India with Eurasia and by the subduction of Pacific Ocean crustal plates under the Asian continent. The area is characterized by extensional, compressional and wrench structural features that comprise most known traps.

Cultural adaptation in translational research: field experiences.

PubMed

Dévieux, Jessy G; Malow, Robert M; Rosenberg, Rhonda; Jean-Gilles, Michèle; Samuels, Deanne; Ergon-Pérez, Emma; Jacobs, Robin

2005-06-01

The increase in the incidence of HIV/AIDS among minorities in the United States and in certain developing nations has prompted new intervention priorities, stressing the adaptation of efficacious interventions for diverse and marginalized groups. The experiences of Florida International University's AIDS Prevention Program in translating HIV primary and secondary prevention interventions among these multicultural populations provide insight into the process of cultural adaptations and address the new scientific emphasis on ecological validity. An iterative process involving forward and backward translation, a cultural linguistic committee, focus group discussions, documentation of project procedures, and consultations with other researchers in the field was used to modify interventions. This article presents strategies used to ensure fidelity in implementing the efficacious core components of evidence-based interventions for reducing HIV transmission and drug use behaviors and the challenges posed by making cultural adaptation for participants with low literacy. This experience demonstrates the importance of integrating culturally relevant material in the translation process with intense focus on language and nuance. The process must ensure that the level of intervention is appropriate for the educational level of participants. Furthermore, the rights of participants must be protected during consenting procedures by instituting policies that recognize the socioeconomic, educational, and systemic pressures to participate in research.

Towards intraoperative assessment of tumor margins in breast surgery using optical coherence elastography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kennedy, Brendan F.; Wijesinghe, Philip; Allen, Wes M.; Chin, Lixin; Latham, Bruce; Saunders, Christobel M.; Sampson, David D.

2016-03-01

Surgical excision of tumor is a critical factor in the management of breast cancer. The most common surgical procedure is breast-conserving surgery. The surgeon's goal is to remove the tumor and a rim of healthy tissue surrounding the tumor: the surgical margin. A major issue in breast-conserving surgery is the absence of a reliable tool to guide the surgeon in intraoperatively assessing the margin. A number of techniques have been proposed; however, the re-excision rate remains high and has been reported to be in the range 30-60%. New tools are needed to address this issue. Optical coherence elastography (OCE) shows promise as a tool for intraoperative tumor margin assessment in breast-conserving surgery. Further advances towards clinical translation are limited by long scan times and small fields of view. In particular, scanning over sufficient areas to assess the entire margin in an intraoperative timeframe has not been shown to be feasible. Here, we present a protocol allowing ~75% of the surgical margins to be assessed within 30 minutes. To achieve this, we have incorporated a 65 mm-diameter (internal), wide-aperture annular piezoelectric transducer, allowing the entire surface of the excised tumor mass to be automatically imaged in an OCT mosaic comprised of 10 × 10 mm tiles. As OCT is effective in identifying adipose tissue, our protocol uses the wide-field OCT to selectively guide subsequent local OCE scanning to regions of solid tissue which often present low contrast in OCT images. We present promising examples from freshly excised human breast tissue.

Set-up uncertainties: online correction with X-ray volume imaging.

PubMed

Kataria, Tejinder; Abhishek, Ashu; Chadha, Pranav; Nandigam, Janardhan

2011-01-01

To determine interfractional three-dimensional set-up errors using X-ray volumetric imaging (XVI). Between December 2007 and August 2009, 125 patients were taken up for image-guided radiotherapy using online XVI. After matching of reference and acquired volume view images, set-up errors in three translation directions were recorded and corrected online before treatment each day. Mean displacements, population systematic (Σ), and random (σ) errors were calculated and analyzed using SPSS (v16) software. Optimum clinical target volume (CTV) to planning target volume (PTV) margin was calculated using Van Herk's (2.5Σ + 0.7 σ) and Stroom's (2Σ + 0.7 σ) formula. Patients were grouped in 4 cohorts, namely brain, head and neck, thorax, and abdomen-pelvis. The mean vector displacement recorded were 0.18 cm, 0.15 cm, 0.36 cm, and 0.35 cm for brain, head and neck, thorax, and abdomen-pelvis, respectively. Analysis of individual mean set-up errors revealed good agreement with the proposed 0.3 cm isotropic margins for brain and 0.5 cm isotropic margins for head-neck. Similarly, 0.5 cm circumferential and 1 cm craniocaudal proposed margins were in agreement with thorax and abdomen-pelvic cases. The calculated mean displacements were well within CTV-PTV margin estimates of Van Herk (90% population coverage to minimum 95% prescribed dose) and Stroom (99% target volume coverage by 95% prescribed dose). Employing these individualized margins in a particular cohort ensure comparable target coverage as described in literature, which is further improved if XVI-aided set-up error detection and correction is used before treatment.

Environmental and ammonoid faunal changes related to Albian Bay of Biscay opening: Insights from the northern margin of the Basque-Cantabrian Basin

NASA Astrophysics Data System (ADS)

Agirrezabala, Luis M.; López-Horgue, Mikel A.

2017-12-01

The opening and ocean floor spreading of the Bay of Biscay began in the earliest Albian. The integrative study of the Albian sedimentary record and its ammonoid fauna (around 250 specimens) from the northern margin of the Basque-Cantabrian Basin indicates that environmental changes, occurred as a consequence of the Bay of Biscay opening, triggered significant ammonoid bioevents. Main bioevents are diversity changes in the ammonoid associations, occurrence of large forms (diameter up to 0.45 m) and the incursion of elements from other basins. Time-correlation of faulting pulses with ammonoid bioevents indicates that transtensive tectonics was ultimately the major control on the marine environmental conditions such as depth, sea bottom physiography, seaways, sedimentary systems and sea-water chemistry. The pulsating faulting during the Albian led to the increment of the subsidence rate, the deepening and widening of the margin and the progressive increase in the oceanic circulation between the margin and the nascent Bay of Biscay and North Atlantic. In addition, Albian synsedimentary faults constituted conduits for ascending magmas and hydrocarbon-rich hydrothermal fluids, which expelled to the seafloor, causing changes in the sediments, the sea-water chemistry (fertilization) and biota. The integration of sedimentological and palaeontological data has given the basis for a conceptual model of the ammonoid habitats.

Validation of the Simple Shoulder Test in a Portuguese-Brazilian population. Is the latent variable structure and validation of the Simple Shoulder Test Stable across cultures?

PubMed

Neto, Jose Osni Bruggemann; Gesser, Rafael Lehmkuhl; Steglich, Valdir; Bonilauri Ferreira, Ana Paula; Gandhi, Mihir; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo

2013-01-01

The validation of widely used scales facilitates the comparison across international patient samples. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. The Simple Shoulder Test was translated from English into Brazilian Portuguese, translated back into English, and evaluated for accuracy by an expert committee. It was then administered to 100 patients with shoulder conditions. Psychometric properties were analyzed including factor analysis, internal reliability, test-retest reliability at seven days, and construct validity in relation to the Short Form 36 health survey (SF-36). Factor analysis demonstrated a three factor solution. Cronbach's alpha was 0.82. Test-retest reliability index as measured by intra-class correlation coefficient (ICC) was 0.84. Associations were observed in the hypothesized direction with all subscales of SF-36 questionnaire. The Simple Shoulder Test translation and cultural adaptation to Brazilian-Portuguese demonstrated adequate factor structure, internal reliability, and validity, ultimately allowing for its use in the comparison with international patient samples.

Validation of the Simple Shoulder Test in a Portuguese-Brazilian Population. Is the Latent Variable Structure and Validation of the Simple Shoulder Test Stable across Cultures?

PubMed Central

Neto, Jose Osni Bruggemann; Gesser, Rafael Lehmkuhl; Steglich, Valdir; Bonilauri Ferreira, Ana Paula; Gandhi, Mihir; Vissoci, João Ricardo Nickenig; Pietrobon, Ricardo

2013-01-01

Background The validation of widely used scales facilitates the comparison across international patient samples. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. Objective The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. Methods The Simple Shoulder Test was translated from English into Brazilian Portuguese, translated back into English, and evaluated for accuracy by an expert committee. It was then administered to 100 patients with shoulder conditions. Psychometric properties were analyzed including factor analysis, internal reliability, test-retest reliability at seven days, and construct validity in relation to the Short Form 36 health survey (SF-36). Results Factor analysis demonstrated a three factor solution. Cronbach’s alpha was 0.82. Test-retest reliability index as measured by intra-class correlation coefficient (ICC) was 0.84. Associations were observed in the hypothesized direction with all subscales of SF-36 questionnaire. Conclusion The Simple Shoulder Test translation and cultural adaptation to Brazilian-Portuguese demonstrated adequate factor structure, internal reliability, and validity, ultimately allowing for its use in the comparison with international patient samples. PMID:23675436

Marginal and internal fit of nano-composite CAD/CAM restorations

PubMed Central

Park, So-Hyun; Shin, Yoo-Jin

2016-01-01

Objectives The purpose of this study was to compare the marginal and internal fit of nano-composite CAD-CAM restorations. Materials and Methods A full veneer crown and an mesio-occluso-distal (MOD) inlay cavity, which were prepared on extracted human molars, were used as templates of epoxy resin replicas. The prepared teeth were scanned and CAD-CAM restorations were milled using Lava Ultimate (LU) and experimental nano-composite CAD/CAM blocks (EB) under the same milling parameters. To assess the marginal and internal fit, the restorations were cemented to replicas and were embedded in an acrylic mold for sectioning at 0.5 mm intervals. The measured gap data were pooled according to the block types and measuring points for statistical analysis. Results Both the block type and measuring point significantly affected gap values, and their interaction was significant (p = 0.000). In crowns and inlays made from the two blocks, gap values were significantly larger in the occlusal area than in the axial area, while gap values in the marginal area were smallest (p < 0.001). Among the blocks, the restorations milled from EB had a significantly larger gap at all measuring points than those milled from LU (p = 0.000). Conclusions The marginal and internal gaps of the two nano-composite CAD/CAM blocks differed according to the measuring points. Among the internal area of the two nano-composite CAD/CAM restorations, occlusal gap data were significantly larger than axial gap data. The EB crowns and inlays had significantly larger gaps than LU restorations. PMID:26877989

Developing Probabilistic Safety Performance Margins for Unknown and Underappreciated Risks

NASA Technical Reports Server (NTRS)

Benjamin, Allan; Dezfuli, Homayoon; Everett, Chris

2015-01-01

Probabilistic safety requirements currently formulated or proposed for space systems, nuclear reactor systems, nuclear weapon systems, and other types of systems that have a low-probability potential for high-consequence accidents depend on showing that the probability of such accidents is below a specified safety threshold or goal. Verification of compliance depends heavily upon synthetic modeling techniques such as PRA. To determine whether or not a system meets its probabilistic requirements, it is necessary to consider whether there are significant risks that are not fully considered in the PRA either because they are not known at the time or because their importance is not fully understood. The ultimate objective is to establish a reasonable margin to account for the difference between known risks and actual risks in attempting to validate compliance with a probabilistic safety threshold or goal. In this paper, we examine data accumulated over the past 60 years from the space program, from nuclear reactor experience, from aircraft systems, and from human reliability experience to formulate guidelines for estimating probabilistic margins to account for risks that are initially unknown or underappreciated. The formulation includes a review of the safety literature to identify the principal causes of such risks.

A Method for Obtaining Large Populations of Synchronized Caenorhabditis elegans Dauer Larvae.

PubMed

Ow, Maria C; Hall, Sarah E

2015-01-01

The C. elegans dauer is an attractive model with which to investigate fundamental biological questions, such as how environmental cues are sensed and are translated into developmental decisions through a series of signaling cascades that ultimately result in a transformed animal. Here we describe a simple method of using egg white plates to obtain highly synchronized purified dauers that can be used in downstream applications requiring large quantities of dauers or postdauer animals.

Prediction of Safety Margin and Optimization of Dosing Protocol for a Novel Antibiotic using Quantitative Systems Pharmacology Modeling.

PubMed

Woodhead, Jeffrey L; Paech, Franziska; Maurer, Martina; Engelhardt, Marc; Schmitt-Hoffmann, Anne H; Spickermann, Jochen; Messner, Simon; Wind, Mathias; Witschi, Anne-Therese; Krähenbühl, Stephan; Siler, Scott Q; Watkins, Paul B; Howell, Brett A

2018-06-07

Elevations of liver enzymes have been observed in clinical trials with BAL30072, a novel antibiotic. In vitro assays have identified potential mechanisms for the observed hepatotoxicity, including electron transport chain (ETC) inhibition and reactive oxygen species (ROS) generation. DILIsym, a quantitative systems pharmacology (QSP) model of drug-induced liver injury, has been used to predict the likelihood that each mechanism explains the observed toxicity. DILIsym was also used to predict the safety margin for a novel BAL30072 dosing scheme; it was predicted to be low. DILIsym was then used to recommend potential modifications to this dosing scheme; weight-adjusted dosing and a requirement to assay plasma alanine aminotransferase (ALT) daily and stop dosing as soon as ALT increases were observed improved the predicted safety margin of BAL30072 and decreased the predicted likelihood of severe injury. This research demonstrates a potential application for QSP modeling in improving the safety profile of candidate drugs. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Experimental Design for the Evaluation of Detection Techniques of Hidden Corrosion Beneath the Thermal Protective System of the Space Shuttle Orbiter

NASA Technical Reports Server (NTRS)

Kammerer, Catherine C.; Jacoby, Joseph A.; Lomness, Janice K.; Hintze, Paul E.; Russell, Richard W.

2007-01-01

The United States Space Operational Space Shuttle Fleet Consists of three shuttles with an average age of 19.7 years. Shuttles are exposed to corrosive conditions while undergoing final closeout for missions at the launch pad and extreme conditions during ascent, orbit, and descent that may accelerate the corrosion process. Structural corrosion under TPS could progress undetected (without tile removal) and eventually result in reduction in structural capability sufficient to create negative margins of . safety and ultimate loss of local structural capability.

Seismogenic rotational slumps and translational glides in pelagic deep-water carbonates. Upper Tithonian-Berriasian of Southern Tethyan margin (W Sicily, Italy)

NASA Astrophysics Data System (ADS)

Basilone, Luca

2017-07-01

Soft-sediment deformation structures (SSDSs), which reflect sediment mobilization processes, are helpful to identify punctual events of paleoenvironmental stresses. In the upper Tithonian-Berriasian calpionellid pelagic limestone of the Lattimusa Fm. outcropping in the Barracù section (W Sicily), paleoenvironmental restoration reveals the occurrence of a deep-water flat basin, characterised by undeformed planar bedding, laterally passing to a gentle slope where the deformed horizons alternate with undeformed beds. Here, two types of gravity slides have been differentiated on the basis of different kinds of SSDSs, brittle deformation, involved lithofacies, geometry and morphology. Type 1 slump sheets, involving marl-limestone couplets, are characterised by chaotic stratification, truncated beds, recumbent folds, tension gashes, clastic dikes and small-scale listric normal faults and thrusts. They moved downslope as a rotational slump, displaying the typical wedge-shaped morphology, becoming thicker toe-wards. Type 2 slump sheets, involving bed packages of lime mudstone, are characterised by arcuate slump scars developing downwards as listric normal faults, associated with rotational beds and bulging. Displaying tabular geometries, they moved coherently along an overall bedding parallel detachment surface as a translational glide characterised by sediment creep. Regional geology indicates that the basin (Sicanian), bordered by a stepped carbonate platform, was affected by synsedimentary tectonics throughout the Mesozoic. The synsedimentary extensional tectonics that affect the Upper Triassic-Jurassic deposits with steeped normal faults, causing tilt-block and instability of the seafloor through fluidization processes, triggered the rotational slumps of the lower portion of the section. Seismic shocks, induced by outside sector tectonics, like those recorded in the adjacent Busambra stepped carbonate platform margin, triggered the rotational slumps that are not related to local-scale faults. To explain the translational glides of the upper portion of the section, the aforementioned outside sector earthquakes produced instability of the sea-floor through thixotropy of marls. In this case, the driving forces (i.e., gravitational) were favoured by the uplifting trend that is well recorded in the Southern Tethyan continental margin. We suggest that the various early deformations represent rotational slump and sediment creep that may be characteristic for slump structures in pelagic carbonates, depending on the involved lithologies (i.e., paleoenvironmental setting) and the intensity/distance of the trigger mechanism (i.e., earthquake epicentre).

Dosimetric consequences of translational and rotational errors in frame-less image-guided radiosurgery

PubMed Central

2012-01-01

Background To investigate geometric and dosimetric accuracy of frame-less image-guided radiosurgery (IG-RS) for brain metastases. Methods and materials Single fraction IG-RS was practiced in 72 patients with 98 brain metastases. Patient positioning and immobilization used either double- (n = 71) or single-layer (n = 27) thermoplastic masks. Pre-treatment set-up errors (n = 98) were evaluated with cone-beam CT (CBCT) based image-guidance (IG) and were corrected in six degrees of freedom without an action level. CBCT imaging after treatment measured intra-fractional errors (n = 64). Pre- and post-treatment errors were simulated in the treatment planning system and target coverage and dose conformity were evaluated. Three scenarios of 0 mm, 1 mm and 2 mm GTV-to-PTV (gross tumor volume, planning target volume) safety margins (SM) were simulated. Results Errors prior to IG were 3.9 mm ± 1.7 mm (3D vector) and the maximum rotational error was 1.7° ± 0.8° on average. The post-treatment 3D error was 0.9 mm ± 0.6 mm. No differences between double- and single-layer masks were observed. Intra-fractional errors were significantly correlated with the total treatment time with 0.7mm±0.5mm and 1.2mm±0.7mm for treatment times ≤23 minutes and >23 minutes (p<0.01), respectively. Simulation of RS without image-guidance reduced target coverage and conformity to 75% ± 19% and 60% ± 25% of planned values. Each 3D set-up error of 1 mm decreased target coverage and dose conformity by 6% and 10% on average, respectively, with a large inter-patient variability. Pre-treatment correction of translations only but not rotations did not affect target coverage and conformity. Post-treatment errors reduced target coverage by >5% in 14% of the patients. A 1 mm safety margin fully compensated intra-fractional patient motion. Conclusions IG-RS with online correction of translational errors achieves high geometric and dosimetric accuracy. Intra-fractional errors decrease target coverage and conformity unless compensated with appropriate safety margins. PMID:22531060

CTSA‐IP: A Solution to Identifying and Aggregating Intellectual Property across the NIH Clinical Translational Science Award (CTSA) Consortium of Biomedical Research Institutes

PubMed Central

Hazard, Mike; Steele, Scott; Wang, Dongwen; Pearson, Thomas; Scheideler, Mark; Dewhurst, Steve

2011-01-01

Abstract  One of the objectives of the Consortium of Institutions with Clinical and Translational Science Awards (CTSAs) is to enhance technology transfer among the CTSAs and with public and private sector partners. Clinical and Translational Sciences Award Intellectual Property (CTSA‐IP; http://www.CTSAIP.org) is a web‐based, open access IP search tool that aggregates and promotes technologies from member institutions of the National Institutes of Health’s (NIH) CTSAs consortium. Its ultimate aim is to stimulate collaborative research activity by encouraging the formation of public‐private partnerships with CTSA institutions and the NIH. First launched in 2009, CTSA‐IP has grown rapidly and met its first objectives of developing wide member institution participation and site usage. This communication will discuss the strategy employed in the initiative of aggregating IP across institutional boundaries, the promise that lies therein, as well as the challenges encountered and lessons learned in promoting CTSA‐wide engagement. Clin Trans Sci 2011; Volume 4: 328–331 PMID:22029803

A road map to Translational Medicine in Qatar and a model for the world

PubMed Central

2012-01-01

Translational Medicine (TM) in Qatar is part of a concerted effort of the Qatari medical and scientific leadership supported by a strong political will by Qatari authorities to deliver world-class health care to Qatari residents while participating in the worldwide quest to bridge the gap between bench-to-bedside-to-community. TM programs should embrace the Qatar National vision for research to become an international hub of excellence in research and development, based on intellectual merit, contributing to global knowledge and adhering to international standards, to innovate by translating new and original ideas into useful applications, to be inclusive at the national and international level, to build and maintain a competitive and diversified economy and ultimately improve the health and well-being of the Qatar’s population. Although this writing focuses on Qatar, we hope that the thoughts expressed here may be of broader use for the development of any TM program particularly in regions where an established academic community surrounded by a rich research infrastructure and/or a vibrant biotechnology enterprise is not already present. PMID:22929646

Putting program evaluation to work: a framework for creating actionable knowledge for suicide prevention practice.

PubMed

Wilkins, Natalie; Thigpen, Sally; Lockman, Jennifer; Mackin, Juliette; Madden, Mary; Perkins, Tamara; Schut, James; Van Regenmorter, Christina; Williams, Lygia; Donovan, John

2013-06-01

The economic and human cost of suicidal behavior to individuals, families, communities, and society makes suicide a serious public health concern, both in the US and around the world. As research and evaluation continue to identify strategies that have the potential to reduce or ultimately prevent suicidal behavior, the need for translating these findings into practice grows. The development of actionable knowledge is an emerging process for translating important research and evaluation findings into action to benefit practice settings. In an effort to apply evaluation findings to strengthen suicide prevention practice, the Centers for Disease Control and Prevention (CDC) and the Substance Abuse and Mental Health Services Administration (SAMHSA) supported the development of three actionable knowledge products that make key findings and lessons learned from youth suicide prevention program evaluations accessible and useable for action. This paper describes the actionable knowledge framework (adapted from the knowledge transfer literature), the three products that resulted, and recommendations for further research into this emerging method for translating research and evaluation findings and bridging the knowledge-action gap.

Managing the innovation supply chain to maximize personalized medicine.

PubMed

Waldman, S A; Terzic, A

2014-02-01

Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient's molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application bridging the bench with the bedside. However, this process also can be viewed through a complementary prism, as a necessary supply chain of services and providers, each making essential contributions to the development of the final product to maximize value to consumers. Considering personalized medicine in this context of supply chain management highlights essential points of vulnerability and/or scalability that can ultimately constrain translation of the biological revolution or potentiate it into individualized diagnostics and therapeutics for optimized value creation and delivery.

Evaluation Metrics for Biostatistical and Epidemiological Collaborations

PubMed Central

Rubio, Doris McGartland; del Junco, Deborah J.; Bhore, Rafia; Lindsell, Christopher J.; Oster, Robert A.; Wittkowski, Knut M.; Welty, Leah J.; Li, Yi-Ju; DeMets, Dave

2011-01-01

Increasing demands for evidence-based medicine and for the translation of biomedical research into individual and public health benefit have been accompanied by the proliferation of special units that offer expertise in biostatistics, epidemiology, and research design (BERD) within academic health centers. Objective metrics that can be used to evaluate, track, and improve the performance of these BERD units are critical to their successful establishment and sustainable future. To develop a set of reliable but versatile metrics that can be adapted easily to different environments and evolving needs, we consulted with members of BERD units from the consortium of academic health centers funded by the Clinical and Translational Science Award Program of the National Institutes of Health. Through a systematic process of consensus building and document drafting, we formulated metrics that covered the three identified domains of BERD practices: the development and maintenance of collaborations with clinical and translational science investigators, the application of BERD-related methods to clinical and translational research, and the discovery of novel BERD-related methodologies. In this article, we describe the set of metrics and advocate their use for evaluating BERD practices. The routine application, comparison of findings across diverse BERD units, and ongoing refinement of the metrics will identify trends, facilitate meaningful changes, and ultimately enhance the contribution of BERD activities to biomedical research. PMID:21284015

Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs).

PubMed

Nagel-Wolfrum, Kerstin; Möller, Fabian; Penner, Inessa; Baasov, Timor; Wolfrum, Uwe

2016-04-01

In recent years, remarkable advances in the ability to diagnose genetic disorders have been made. The identification of disease-causing genes allows the development of gene-specific therapies with the ultimate goal to develop personalized medicines for each patient according to their own specific genetic defect. In-depth genotyping of many different genes has revealed that ~12% of inherited genetic disorders are caused by in-frame nonsense mutations. Nonsense (non-coding) mutations are caused by point mutations, which generate premature termination codons (PTCs) that cause premature translational termination of the mRNA, and subsequently inhibit normal full-length protein expression. Recently, a gene-based therapeutic approach for genetic diseases caused by nonsense mutations has emerged, namely the so-called translational read-through (TR) therapy. Read-through therapy is based on the discovery that small molecules, known as TR-inducing drugs (TRIDs), allow the translation machinery to suppress a nonsense codon, elongate the nascent peptide chain, and consequently result in the synthesis of full-length protein. Several TRIDs are currently under investigation and research has been performed on several genetic disorders caused by nonsense mutations over the years. These findings have raised hope for the usage of TR therapy as a gene-based pharmacogenetic therapy for nonsense mutations in various genes responsible for a variety of genetic diseases.

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Reevaluating the Potential of Mouse Models for the Human Immune System.

PubMed

Jameson, Stephen C; Masopust, David

2018-04-02

Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans. Alternative approaches are discussed that may extend the use of the mouse model for preclinical studies. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Nutritional Translation Blended With Food Science: 21st Century Applications1234

PubMed Central

Ferruzzi, Mario G.; Peterson, Devin G.; Singh, R. Paul; Schwartz, Steven J.; Freedman, Marjorie R.

2012-01-01

This paper, based on the symposium “Real-World Nutritional Translation Blended With Food Science,” describes how an integrated “farm-to-cell” approach would create the framework necessary to address pressing public health issues. The paper describes current research that examines chemical reactions that may influence food flavor (and ultimately food consumption) and posits how these reactions can be used in health promotion; it explains how mechanical engineering and computer modeling can study digestive processes and provide better understanding of how physical properties of food influence nutrient bioavailability and posits how this research can also be used in the fight against obesity and diabetes; and it illustrates how an interdisciplinary scientific collaboration led to the development of a novel functional food that may be used clinically in the prevention and treatment of prostate cancer. PMID:23153735

Drug design and discovery: translational biomedical science varies among countries.

PubMed

Weaver, Ian N; Weaver, Donald F

2013-10-01

Drug design and discovery is an innovation process that translates the outcomes of fundamental biomedical research into therapeutics that are ultimately made available to people with medical disorders in many countries throughout the world. To identify which nations succeed, exceed, or fail at the drug design/discovery endeavor--more specifically, which countries, within the context of their national size and wealth, are "pulling their weight" when it comes to developing medications targeting the myriad of diseases that afflict humankind--we compiled and analyzed a comprehensive survey of all new drugs (small molecular entities and biologics) approved annually throughout the world over the 20-year period from 1991 to 2010. Based upon this analysis, we have devised prediction algorithms to ascertain which countries are successful (or not) in contributing to the worldwide need for effective new therapeutics. © 2013 Wiley Periodicals, Inc.

Deposition of Franciscan Complex cherts along the paleoequator and accretion to the American margin at tropical paleolatitudes

USGS Publications Warehouse

Hagstrum, J.T.; Murchey, B.L.

1993-01-01

Red radiolarian cherts from three localities within the Franciscan subduction complex of northern California contain three components of remanent magnetization which are best isolated by progressive thermal demagnetization. The available paleomagnetic, biostratigraphic, and geochemical data indicate deposition of these cherts along the paleoequator (0??-2??N or S paleolatitude) between Pliensbachian and Oxfordian time as the oceanic plate moved eastward, relative to North America, beneath the equatorial zone of high biologic productivity. The chert sequences were subsequently accreted to the American continental margin. Plate reconstruction models for the Farallon plate corrobotate low-paleolatitude trajectories from ridge crest to subduction zone, and they imply subsequent northward translation of the Franciscan Complex by strike-slip faulting related to relative motions between the Farallon, Kula, Pacific, and North American plates. -from Authors

Spatial Control of Gene Expression by miR319-Regulated TCP Transcription Factors in Leaf Development.

PubMed

Bresso, Edgardo G; Chorostecki, Uciel; Rodriguez, Ramiro E; Palatnik, Javier F; Schommer, Carla

2018-02-01

The characteristic leaf shapes we see in all plants are in good part the outcome of the combined action of several transcription factor networks that translate into cell division activity during the early development of the organ. We show here that wild-type leaves have distinct transcriptomic profiles in center and marginal regions. Certain transcripts are enriched in margins, including those of CINCINNATA -like TCPs ( TEOSINTE BRANCHED, CYCLOIDEA and PCF1/2 ) and members of the NGATHA and STYLISH gene families. We study in detail the contribution of microRNA319 (miR319)-regulated TCP transcription factors to the development of the center and marginal regions of Arabidopsis ( Arabidopsis thaliana ) leaves. We compare in molecular analyses the wild type, the tcp2 tcp4 mutant that has enlarged flat leaves, and the tcp2 tcp3 tcp4 tcp10 mutant with strongly crinkled leaves. The different leaf domains of the tcp mutants show changed expression patterns for many photosynthesis-related genes, indicating delayed differentiation, especially in the marginal parts of the organ. At the same time, we found an up-regulation of cyclin genes and other genes that are known to participate in cell division, specifically in the marginal regions of tcp2 tcp3 tcp4 tcp10 Using GUS reporter constructs, we confirmed extended mitotic activity in the tcp2 tcp3 tcp4 tcp10 leaf, which persisted in small defined foci in the margins when the mitotic activity had already ceased in wild-type leaves. Our results describe the role of miR319-regulated TCP transcription factors in the coordination of activities in different leaf domains during organ development. © 2018 American Society of Plant Biologists. All Rights Reserved.

Biophysics, environmental stochasticity, and the evolution of thermal safety margins in intertidal limpets.

PubMed

Denny, M W; Dowd, W W

2012-03-15

As the air temperature of the Earth rises, ecological relationships within a community might shift, in part due to differences in the thermal physiology of species. Prediction of these shifts - an urgent task for ecologists - will be complicated if thermal tolerance itself can rapidly evolve. Here, we employ a mechanistic approach to predict the potential for rapid evolution of thermal tolerance in the intertidal limpet Lottia gigantea. Using biophysical principles to predict body temperature as a function of the state of the environment, and an environmental bootstrap procedure to predict how the environment fluctuates through time, we create hypothetical time-series of limpet body temperatures, which are in turn used as a test platform for a mechanistic evolutionary model of thermal tolerance. Our simulations suggest that environmentally driven stochastic variation of L. gigantea body temperature results in rapid evolution of a substantial 'safety margin': the average lethal limit is 5-7°C above the average annual maximum temperature. This predicted safety margin approximately matches that found in nature, and once established is sufficient, in our simulations, to allow some limpet populations to survive a drastic, century-long increase in air temperature. By contrast, in the absence of environmental stochasticity, the safety margin is dramatically reduced. We suggest that the risk of exceeding the safety margin, rather than the absolute value of the safety margin, plays an underappreciated role in the evolution of thermal tolerance. Our predictions are based on a simple, hypothetical, allelic model that connects genetics to thermal physiology. To move beyond this simple model - and thereby potentially to predict differential evolution among populations and among species - will require significant advances in our ability to translate the details of thermal histories into physiological and population-genetic consequences.

Time to connect: bringing social context into addiction neuroscience

PubMed Central

Heilig, Markus; Epstein, David H.; Nader, Michael A.; Shaham, Yavin

2017-01-01

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant. PMID:27277868

Time to connect: bringing social context into addiction neuroscience.

PubMed

Heilig, Markus; Epstein, David H; Nader, Michael A; Shaham, Yavin

2016-09-01

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.

Magnetic bearings for a high-performance optical disk buffer, volume 1

NASA Technical Reports Server (NTRS)

Hockney, Richard; Adler, Karen; Anastas, George, Jr.; Downer, James; Flynn, Frederick; Goldie, James; Gondhalekar, Vijay; Hawkey, Timothy; Johnson, Bruce

1990-01-01

The innovation investigated in this project was the application of magnetic bearing technology to the translator head of an optical-disk data storage device. Both the capability for space-based applications and improved performance are expected to result. The phase 1 effort produced: (1) detailed specifications for both the translator-head and rotary-spindel bearings; (2) candidate hardware configurations for both bearings with detail definition for the translator head; (3) required characteristics for the magnetic bearing control loops; (4) position sensor selection; and (5) definition of the required electronic functions. The principal objective of Phase 2 was the design, fabrication, assembly, and test of the magnetic bearing system for the translator head. The scope of work included: (1) mechanical design of each of the required components; (2) electrical design of the required circuitry; (3) fabrication of the component parts and bread-board electronics; (4) generation of a test plan; and (5) integration of the prototype unit and performance testing. The project has confirmed the applicability of magnetic bearing technology to suspension of the translator head of the optical disk device, and demonstrated the achievement of all performance objectives. The magnetic bearing control loops perform well, achieving 100 Hz nominal bandwidth with phase margins between 37 and 63 degrees. The worst-case position resolution is 0.02 micron in the displacement loops and 1 micron rad in the rotation loops, The system is very robust to shock disturbances, recovering smoothly even when collisions occur between the translator and frame. The unique start-up/shut-down circuit has proven very effective.

Advancing Understanding of Earthquakes by Drilling an Eroding Convergent Margin

NASA Astrophysics Data System (ADS)

von Huene, R.; Vannucchi, P.; Ranero, C. R.

2010-12-01

A program of IODP with great societal relevance is sampling and instrumenting the seismogenic zone. The zone generates great earthquakes that trigger tsunamis, and submarine slides thereby endangering coastal communities containing over sixty percent of the earth’s population. To asses and mitigate this endangerment it is urgent to advance understanding of fault dynamics that allows more timely anticipation of hazardous seismicity. Seismogenesis on accreting and eroding convergent plate boundaries apparently differ because of dissimilar materials along the interplate fault. As the history of instrumentally recorded earthquakes expands the difference becomes clearer. The more homogeneous clay, silt and sand subducted at accreting margins is associated with great earthquakes (M 9) whereas the fragmented upper plate rock that can dominate subducted material along an eroding margin plate interface is associated with many tsunamigenic earthquakes (Bilek, 2010). Few areas have been identified where the seismogenic zone can be reached with scientific drilling. In IODP accreting margins are studied on the NanTroSeize drill transect off Japan where the ultimate drilling of the seismogenic interface may occur by the end of IODP. The eroding Costa Rica margin will be studied in CRISP where a drill program will begin in 2011. The Costa Rican geophysical site survey will be complete with acquisition and processing of 3D seismic data in 2011 but the entire drilling will not be accomplished in IODP. It is appropriate that the accreting margin study be accomplished soon considering the indications of a pending great earthquake that will affect a country that has devoted enormous resources to IODP. However, understanding the erosional end-member is scientifically as important to an understanding of fault mechanics. Transoceanic tsunamis affect the entire Pacific rim where most subduction zones are eroding margins. The Costa Rican subduction zone is less complex operationally and perhaps geologically than the Nankai margin. The developing Central American countries do not have the resources to contribute to IODP but this should not deter acquiring the scientific insights proposed in CRISP considering the broader scientific benefits. Such benefits include the first sampling and instrumentation of an actively eroding plate interface and drilling near or into an earthquake asperity. Drilling an eroding margin should significantly advance understanding of subduction zone fault mechanisms and help improve assessment of future hazardous earthquakes and tsunamis.

Biomechanical comparison of suture anchor versus margin convergence plus suture anchor for rotator cuff repair.

PubMed

Chen, Shi-yi; Malcarney, Hilary L; Murrell, George A C

2009-02-01

To evaluate results of margin convergence versus suture anchors in rotator cuff repair, and to determine which method is mechanically superior. Eighteen kangaroo shoulders were randomly divided into three groups (n = 6). A full thickness tendon defect 1.0 cm × 1.5 cm in size was created in the supraspinatus tendon at humeral insertion, simulating a massive rotator cuff tear. Three different techniques were employed for rotator cuff repair: (i) Mitek GII suture anchor alone (Group 1); (ii) margin convergence alone (Group 2); and (iii) margin convergence plus Mitek GII suture anchor (Group 3). Combined loads were applied to each specimen. After completion of cyclic loading, the construct was loaded to failure. ANOVA and LSD (Least Significant Difference) multiple comparisons of the means were applied to results. Cyclic load testing showed progressive gap formation in each repaired specimen with increasing cycles. Group 1 reached 50% failure at an average of 34 cycles, Group 2 at 75 cycles and Group 3 at 73 cycles. There were significant difference between Groups 1 and 2, and Groups 1 and 3 (P ≤ 0.001). After 100 loading cycles, the average gap size was 6.8 mm, 6.1 mm and 4.7 mm in Groups 1, 2 and 3, respectively. There was a significant difference between Groups 1 and 3 (P ≤ 0.015). All specimens eventually reached failure. Rotator cuff repairs with margin convergence +/- suture anchor were far stronger than suture anchor alone, both in gap formation and ultimate failure load. However, progressive gap formation with cyclic loading seems inevitable after cuff repair, which may facilitate clinical understanding of the phenomena of re-tear or residual defect. © 2009 Tianjin Hospital and Blackwell Publishing Asia Pty Ltd.

Extreme hepatic resections for the treatment of advanced hepatoblastoma: Are planned close margins an acceptable approach?

PubMed

Fonseca, Adriana; Gupta, Abha; Shaikh, Furqan; Ramphal, Raveena; Ng, Vicky; McGilvray, Ian; Gerstle, J Ted

2018-02-01

Orthotopic liver transplantation (OLT) is considered the standard for children with hepatoblastoma (HB) in whom complete surgical resection is not possible. However, OLT is not always available or feasible. To describe the outcome of children with HB who were initially deemed unresectable and underwent complex hepatectomy with planned close margins, and ultimately avoided OLT. Demographic data, surgical and pathologic details, and survival information were collected from children treated for HB between January 2010 to December 2015. Among six children (median age 12 months (3-41 months)), PRETEXT classification was III (n = 2), III/IV (n = 1), and IV (n = 3). Patients received a median of six cycles (range 4-7) of platinum-based induction chemotherapy; five received doxorubicin. Experienced pediatric surgeons performed extended right and left hepatectomy in five and one patients, respectively, with assistance of an experienced liver transplant surgeon (n = 4). Microscopic margins were positive (n = 2) and negative but close (n = 4; 2-5 mm). Two patients required vascular reconstruction of the vena cava. At median follow-up of 3.3 years (1.7-4.6 years), there was no evidence of local recurrence. One patient had recurrence of pulmonary disease 3 months after surgery. Patients with advanced HB treated with complex surgical resections with positive or close negative margins had good outcomes without OLT. We suggest that planned positive or close microscopic margins in highly selected HB patients may spare the morbidity of OLT and offer an alternative for those ineligible for OLT. Our experience illustrates the importance of a multidisciplinary team specialized in the management of liver tumors. © 2017 Wiley Periodicals, Inc.

Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise.

PubMed

Healy, E; Brown, S J; Langan, S M; Nicholls, S G; Shams, K; Reynolds, N J

2015-11-01

Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2000 different skin diseases; thus, there are considerable challenges in seeking to undertake research on each of these disorders. This electronic Delphi (e-Delphi) exercise was conducted in order to generate a list of translational dermatology research questions that are regarded as a priority for further investigations. During the first phase of the e-Delphi exercise, 228 research questions were generated by an expert panel that included clinical academic dermatologists, clinical dermatologists, nonclinical scientists, dermatology trainees and representatives from patient support groups. Following completion of the second and third phases, 40 questions on inflammatory skin disease, 20 questions on structural skin disorders/genodermatoses, 37 questions on skin cancer and eight miscellaneous questions were designated as priority translational dermatology research questions (PRQs). In addition to PRQs on a variety of disease areas (including multiple PRQs on psoriasis, eczema, squamous cell carcinoma and melanoma), there were a number of cross-cutting themes that identified a need to investigate mechanisms/pathogenesis of disease and the necessity to improve treatments for patients with skin disease. It is predicted that this list of PRQs will help to provide a strategic direction for translational dermatology research in the U.K. and that addressing this list of questions will ultimately provide clinical benefit for substantial numbers of patients with skin disorders. © 2015 British Association of Dermatologists.

Identification of Translational Dermatology Research Priorities in the UK; Results of an e-Delphi Exercise

PubMed Central

Healy, E.; Reynolds, N.J.

2016-01-01

Summary Background Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2,000 different skin diseases, thus there are considerable challenges in seeking to undertake research on each of these disorders. Objective This eDelphi exercise was conducted in order to generate a list of translational dermatology research questions which are regarded as a priority for further investigations. Results During the first phase of the eDelphi, 228 research questions were generated by an expert panel which included clinical academic dermatologists, clinical dermatologists, non-clinical scientists, dermatology trainees and representatives from patient support groups. Following completion of the second and third phases, 40 questions on inflammatory skin disease, 20 questions on structural skin disorders / genodermatoses, 37 questions on skin cancer and 8 miscellaneous questions were designated as priority translational dermatology research questions (PRQs). In addition to PRQs on a variety of disease areas (including multiple PRQs on psoriasis, eczema, squamous cell carcinoma (SCC) and melanoma), there were a number of cross-cutting themes which identified a need to investigate mechanisms / pathogenesis of disease and the necessity to improve treatments for patients with skin disease. Conclusion It is predicted that this list of PRQs will help to provide a strategic direction for translational dermatology research in the UK and that addressing this list of questions will ultimately provide clinical benefit for substantial numbers of subjects with skin disorders. PMID:26149834

Can we constrain postglacial sedimentation in the western Arctic Ocean by ramped pyrolysis 14C? A case study from the Chukchi-Alaskan margin.

NASA Astrophysics Data System (ADS)

Suzuki, K.; Yamamoto, M.; Rosenheim, B. E.; Omori, T.; Polyak, L.; Nam, S. I.

2017-12-01

The Arctic Ocean underwent dramatic climate changes in the past. Variations in sea-ice extent and ocean current system in the Arctic cause changes in surface albedo and deep water formation, which have global climatic implications. However, Arctic paleoceanographic studies are lagging behind the other oceans due largely to chronostratigraphic difficulties. One of the reasons for this is a scant presence of material suitable for 14C dating in large areas of the Arctic seafloor. To enable improved age constraints for sediments impoverished in datable material, we apply ramped pyrolysis 14C method (Ramped PyrOx 14C, Rosenheim et al., 2008) to sedimentary records from the Chukchi-Alaska margin recovering Holocene to late-glacial deposits. Samples were divided into five fraction products by gradual heating sedimentary organic carbon from ambient laboratory temperature to 1000°C. The thermographs show a trimodal pattern of organic matter decomposition over temperature, and we consider that CO2 generated at the lowest temperature range was derived from autochthonous organic carbon contemporaneous with sediment deposition, similar to studies in the Antarctic margin and elsewhere. For verification of results, some of the samples treated for ramped pyrolysis 14C were taken from intervals dated earlier by AMS 14C using bivalve mollusks. Ultimately, our results allow a new appraisal of deglacial to Holocene deposition at the Chukchi-Alaska margin with potential to be applied to other regions of the Arctic Ocean.

Tectonics of formation, translation, and dispersal of the Coast Range ophiolite of California

USGS Publications Warehouse

McLaughlin, R.J.; Blake, M.C.; Griscom, A.; Blome, C.D.; Murchey, B.

1988-01-01

Data from the Coast Range ophiolite and its tectonic outliers in the northern California Coast Ranges suggest that the lower part of the ophiolite formed 169 to 163 Ma in a forearc or back arc setting at equatorial latitudes. Beginning about 156 Ma and continuing until 145 Ma, arc magmatism was superimposed on the ophiolite, and concurrently, a transform developed along the arc axis or in the back arc area. Rapid northward translation of this rifted active magmatic arc to middle latitudes culminated in its accretion to the California margin of North America at about 145 Ma. This Late Jurassic episode of translation, arc magmatism, and accretion coincided with the Nevadan orogeny and a proposed major plate reorganization in the eastern Pacific basin. Displacement occurred between about 60 and 52 Ma. Ophiolitic rocks in the Decatur terrane of western Washington that have recently been correlated with the Coast Range ophiolite and the Great Valley sequence of California were apparently displaced at least 950 to 1200 km from the west side of the Great Valley between early Tertiary and Early Cretaceous time. Derived rates of northward translation for the ophiolite outliers in California are in the range of 1 to 4 cm/yr. -from Authors

Gravity Probe B spacecraft description

NASA Astrophysics Data System (ADS)

Bennett, Norman R.; Burns, Kevin; Katz, Russell; Kirschenbaum, Jon; Mason, Gary; Shehata, Shawky

2015-11-01

The Gravity Probe B spacecraft, developed, integrated, and tested by Lockheed Missiles & Space Company and later Lockheed Martin Corporation, consisted of structures, mechanisms, command and data handling, attitude and translation control, electrical power, thermal control, flight software, and communications. When integrated with the payload elements, the integrated system became the space vehicle. Key requirements shaping the design of the spacecraft were: (1) the tight mission timeline (17 months, 9 days of on-orbit operation), (2) precise attitude and translational control, (3) thermal protection of science hardware, (4) minimizing aerodynamic, magnetic, and eddy current effects, and (5) the need to provide a robust, low risk spacecraft. The spacecraft met all mission requirements, as demonstrated by dewar lifetime meeting specification, positive power and thermal margins, precision attitude control and drag-free performance, reliable communications, and the collection of more than 97% of the available science data.

Comparative Evaluation of Marginal Adaptation and Fracture Strength of Different Ceramic Inlays Produced by CEREC Omnicam and Heat-Pressed Technique.

PubMed

Oz, F D; Bolay, S

2018-01-01

The aim of this in vitro study was to evaluate marginal adaptation and fracture strength of inlays produced by CEREC Omnicam using different types of blocs and heat-pressed technique. Methods: Seventy-five extracted human mandibular molars were divided randomly into 5 groups ( n =15). 60 molars in four groups received MOD inlay preparations. Experimental groups were CO: Intact teeth, EC: IPS e.max CAD and CEREC, LU: Lava Ultimate and CEREC, EL: IPS Empress CAD and CEREC, EP: IPS Empress Esthetic ingots and heat-pressed technique. Marginal gap measurements were taken with a stereomicroscope. Restorations were cemented with Variolink N and stored in distilled water at 37°C for 24 hours. All samples were subjected to thermocycling. The fracture strength of specimens was determined at a 0.5 mm/min crosshead speed until fracture. Fracture modes were determined. Statistical analyses were performed using one-way analysis of variance for fracture strength data and Kruskal-Wallis for marginal gap data ( p =0.05). The mean marginal gap size of EC, LU, EL, and EP were 33.54  µ m, 33.77  µ m, 34.23  µ m, and 85.34  µ m, respectively. EP had statistically higher values than other groups. The fracture strength values were significantly higher in the intact teeth group (3959,00 ± 1279,79 N) than those of restored groups EC (2408,00 ± 607,97 N), LU (2206,73 ± 675,16), EL (2573.27 ± 644,73) ve EP (2879,53 ± 897,30). Inlays fabricated using CEREC Omnicam demonstrated better marginal adaptation than inlays produced with heat-pressed technique, whereas fracture strength values of inlays fabricated with different type of blocks using CEREC Omnicam exhibited similarity to those fabricated with heat-pressed technique.

Comparative Evaluation of Marginal Adaptation and Fracture Strength of Different Ceramic Inlays Produced by CEREC Omnicam and Heat-Pressed Technique

PubMed Central

Bolay, S.

2018-01-01

Objective The aim of this in vitro study was to evaluate marginal adaptation and fracture strength of inlays produced by CEREC Omnicam using different types of blocs and heat-pressed technique. Methods: Seventy-five extracted human mandibular molars were divided randomly into 5 groups (n=15). 60 molars in four groups received MOD inlay preparations. Experimental groups were CO: Intact teeth, EC: IPS e.max CAD and CEREC, LU: Lava Ultimate and CEREC, EL: IPS Empress CAD and CEREC, EP: IPS Empress Esthetic ingots and heat-pressed technique. Marginal gap measurements were taken with a stereomicroscope. Restorations were cemented with Variolink N and stored in distilled water at 37°C for 24 hours. All samples were subjected to thermocycling. The fracture strength of specimens was determined at a 0.5 mm/min crosshead speed until fracture. Fracture modes were determined. Statistical analyses were performed using one-way analysis of variance for fracture strength data and Kruskal–Wallis for marginal gap data (p=0.05). Results The mean marginal gap size of EC, LU, EL, and EP were 33.54 µm, 33.77 µm, 34.23 µm, and 85.34 µm, respectively. EP had statistically higher values than other groups. The fracture strength values were significantly higher in the intact teeth group (3959,00 ± 1279,79 N) than those of restored groups EC (2408,00 ± 607,97 N), LU (2206,73 ± 675,16), EL (2573.27 ± 644,73) ve EP (2879,53 ± 897,30). Conclusion Inlays fabricated using CEREC Omnicam demonstrated better marginal adaptation than inlays produced with heat-pressed technique, whereas fracture strength values of inlays fabricated with different type of blocks using CEREC Omnicam exhibited similarity to those fabricated with heat-pressed technique. PMID:29853894

Mesozoic architecture of a tract of the European-Iberian continental margin: Insights from preserved submarine palaeotopography in the Longobucco Basin (Calabria, Southern Italy)

NASA Astrophysics Data System (ADS)

Santantonio, Massimo; Fabbi, Simone; Aldega, Luca

2016-01-01

The sedimentary successions exposed in northeast Calabria document the Jurassic-Early Cretaceous tectonic-sedimentary evolution of a former segment of the European-Iberian continental margin. They are juxtaposed today to units representing the deformation of the African and Adriatic plates margins as a product of Apenninic crustal shortening. A complex pattern of unconformities reveals a multi-stage tectonic evolution during the Early Jurassic, which affected the facies and geometries of siliciclastic and carbonate successions deposited in syn- and post-rift environments ranging from fluvial to deep marine. Late Sinemurian/Early Pliensbachian normal faulting resulted in exposure of the Hercynian basement at the sea-floor, which was onlapped by marine basin-fill units. Shallow-water carbonate aprons and reefs developed in response to the production of new accommodation space, fringing the newborn islands which represent structural highs made of Paleozoic crystalline and metamorphic rock. Their drowning and fragmentation in the Toarcian led to the development of thin caps of Rosso Ammonitico facies. Coeval to these deposits, a thick (> 1 km) hemipelagic/siliciclastic succession was sedimented in neighboring hanging wall basins, which would ultimately merge with the structural high successions. Footwall blocks of the Early Jurassic rift, made of Paleozoic basement and basin-margin border faults with their onlapping basin-fill formations, are found today at the hanging wall of Miocene thrusts, overlying younger (Middle/Late Jurassic to Late Paleogene) folded basinal sediments. This paper makes use of selected case examples to describe the richly diverse set of features, ranging from paleontology to sedimentology, to structural geology, which are associated with the field identification of basin-margin unconformities. Our data provide key constraints for restoring the pre-orogenic architecture of a continental margin facing a branch of the Liguria-Piedmont ocean in the Western Tethys, and for estimating displacements and slip rates along synsedimentary faults.

Comparison of Dose Decrement from Intrafraction Motion for Prone and Supine Prostate Radiotherapy

PubMed Central

Olsen, Jeffrey; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-01-01

Background and Purpose Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Material and Methods Electromagnetic tracking data was analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0, 3, and 5 mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on to model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Results Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0 mm margins (p=0.002). No significant differences were found using 5 mm margins. Conclusions Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. PMID:22809590

Comparison of dose decrement from intrafraction motion for prone and supine prostate radiotherapy.

PubMed

Olsen, Jeffrey R; Parikh, Parag J; Watts, Michael; Noel, Camille E; Baker, Kenneth W; Santanam, Lakshmi; Michalski, Jeff M

2012-08-01

Dose effects of intrafraction motion during prone prostate radiotherapy are unknown. We compared prone and supine treatment using real-time tracking data to model dose coverage. Electromagnetic tracking data were analyzed for 10 patients treated prone, and 15 treated supine, with IMRT for localized prostate cancer. Plans were generated using 0 mm, 3 mm, and 5mm PTV expansions. Manual beam-hold interventions were applied to reposition the patient when translations exceeded a predetermined threshold. A custom software application (SWIFTER) used intrafraction tracking data acquired during beam-on model delivered prostate dose, by applying rigid body transformations to the prostate structure contoured at simulation within the planned dose cloud. The delivered minimum prostate dose as a percentage of planned dose (Dmin%), and prostate volume covered by the prescription dose as a percentage of the planned volume (VRx%) were compared for prone and supine treatment. Dmin% was reduced for prone treatment for 0 (p=0.02) and 3 mm (p=0.03) PTV margins. VRx% was reduced for prone treatment only for 0mm margins (p=0.002). No significant differences were found using 5 mm margins. Intrafraction motion has a greater impact on target coverage for prone compared to supine prostate radiotherapy. PTV margins of 3 mm or less correlate with a significant decrease in delivered dose for prone treatment. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A study of longitudinal tumor motion in helical tomotherapy using a cylindrical phantom

PubMed Central

Klein, Michael; Gaede, Stewart

2013-01-01

Tumor motion during radiation treatment on a helical tomotherapy unit may create problems due to interplay with motion of the multileaf collimator, gantry rotation, and patient couch translation through the gantry. This study evaluated this interplay effect for typical clinical parameters using a cylindrical phantom consisting of 1386 diode detectors placed on a respiratory motion platform. All combinations of radiation field widths (1, 2.5, and 5 cm) and gantry rotation periods (16, 30, and 60 s) were considered for sinusoidal motions with a period of 4 s and amplitudes of 5, 6, 7, 8, 9, and 10 mm, as well as real patient breathing pattern. Gamma comparisons with 2% dose difference and 2 mm distance to agreement and dose profiles were used for evaluation. The required motion margins were determined for each set of parameters. The required margin size increased with decreasing field width and increasing tumor motion amplitude, but was not affected by rotation period. The plans with the smallest field width of 1 cm have required motion margins approximately equal to the amplitude of motion (±25%), while those with the largest field width of 5 cm had required motion margins approximately equal to 20% of the motion amplitude (±20%). For tumor motion amplitudes below 6 mm and field widths above 1 cm, the required additional motion margins were very small, at a maximum of 2.5 mm for sinusoidal breathing patterns and 1.2 mm for the real patient breathing pattern. PACS numbers: 87.55.km, 87.55.Qr, 87.56.Fc

Intraoperative imaging during Mohs surgery with reflectance confocal microscopy: initial clinical experience

NASA Astrophysics Data System (ADS)

Flores, Eileen S.; Cordova, Miguel; Kose, Kivanc; Phillips, William; Rossi, Anthony; Nehal, Kishwer; Rajadhyaksha, Milind

2015-06-01

Mohs surgery for the removal of nonmelanoma skin cancers (NMSCs) is performed in stages, while being guided by the examination for residual tumor with frozen pathology. However, preparation of frozen pathology at each stage is time consuming and labor intensive. Real-time intraoperative reflectance confocal microscopy (RCM), combined with video mosaicking, may enable rapid detection of residual tumor directly in the surgical wounds on patients. We report our initial experience on 25 patients, using aluminum chloride for nuclear contrast. Imaging was performed in quadrants in the wound to simulate the Mohs surgeon's examination of pathology. Images and videos of the epidermal and dermal margins were found to be of clinically acceptable quality. Bright nuclear morphology was identified at the epidermal margin and detectable in residual NMSC tumors. The presence of residual tumor and normal skin features could be detected in the peripheral and deep dermal margins. Intraoperative RCM imaging may enable detection of residual tumor directly on patients during Mohs surgery, and may serve as an adjunct for frozen pathology. Ultimately, for routine clinical utility, a stronger tumor-to-dermis contrast may be necessary, and also a smaller microscope with an automated approach for imaging in the entire wound in a rapid and controlled manner.

Assessing global resource utilization efficiency in the industrial sector.

PubMed

Rosen, Marc A

2013-09-01

Designing efficient energy systems, which also meet economic, environmental and other objectives and constraints, is a significant challenge. In a world with finite natural resources and large energy demands, it is important to understand not just actual efficiencies, but also limits to efficiency, as the latter identify margins for efficiency improvement. Energy analysis alone is inadequate, e.g., it yields energy efficiencies that do not provide limits to efficiency. To obtain meaningful and useful efficiencies for energy systems, and to clarify losses, exergy analysis is a beneficial and useful tool. Here, the global industrial sector and industries within it are assessed by using energy and exergy methods. The objective is to improve the understanding of the efficiency of global resource use in the industrial sector and, with this information, to facilitate the development, prioritization and ultimate implementation of rational improvement options. Global energy and exergy flow diagrams for the industrial sector are developed and overall efficiencies for the global industrial sector evaluated as 51% based on energy and 30% based on exergy. Consequently, exergy analysis indicates a less efficient picture of energy use in the global industrial sector than does energy analysis. A larger margin for improvement exists from an exergy perspective, compared to the overly optimistic margin indicated by energy. Copyright © 2012 Elsevier B.V. All rights reserved.

Combined multispectral spatial frequency domain imaging and computed tomography system for intraoperative breast tumor margin assessment

NASA Astrophysics Data System (ADS)

McClatchy, D. M.; Rizzo, E. J.; Krishnaswamy, V.; Kanick, S. C.; Wells, W. A.; Paulsen, K. D.; Pogue, B. W.

2017-02-01

There is a dire clinical need for surgical margin guidance in breast conserving therapy (BCT). We present a multispectral spatial frequency domain imaging (SFDI) system, spanning the visible and near-infrared (NIR) wavelengths, combined with a shielded X-ray computed tomography (CT) system, designed for intraoperative breast tumor margin assessment. While the CT can provide a volumetric visualization of the tumor core and its spiculations, the co-registered SFDI can provide superficial and quantitative information about localized changes tissue morphology from light scattering parameters. These light scattering parameters include both model-based parameters of sub-diffusive light scattering related to the particle size scale distribution and also textural information of the high spatial frequency reflectance. Because the SFDI and CT components are rigidly fixed, a simple transformation can be used to simultaneously display the SFDI and CT data in the same coordinate system. This is achieved through the Visualization Toolkit (vtk) file format in the open-source Slicer medical imaging software package. In this manuscript, the instrumentation, data processing, and preliminary human specimen data will be presented. The ultimate goal of this work is to evaluate this technology in a prospective clinical trial, and the current limitations and engineering solutions to meet this goal will also be discussed.

Diversity of ophiolites and obduction processes: examples from Eastern Tethyan regions and New Caledonia.

NASA Astrophysics Data System (ADS)

Whitechurch, Hubert; Agard, Philippe; Ulrich, Marc

2015-04-01

Diversity of ophiolites and obduction processes: examples from Eastern Tethyan regions and New Caledonia. Whitechurch H.(1) Agard P.(2), Ulrich M.(1) (1) EOST - University of Strasbourg (France) (2) ISTeP - University Pierre et Marie Curie, Paris (France) Ophiolites are considered as pieces of oceanic lithosphere that escaped subduction to be obducted on continental margins. After the Penrose Conference in 1972, they have all been regarded as issued from mid-ocean ridges of large oceans. Subsequently, most of ophiolites have been considered as generated in supra-subduction zone (SSZ) environment, mainly on the basis of geochemical arguments. However, this characterization encompasses very different geological situations, somewhat in contradiction with a univocal geochemical interpretation, both in terms of where ophiolite formed (i.e., ocean-continent transition zones, ocean ridges, marginal basins) and were obducted (contrasting nature of the margins). Examples from eastern Mesozoic Tethyan ophiolites (Cyprus, Turkey, Syria, Iran, Oman) and tertiary New Caledonia ophiolites all show this diversity, both in their internal structures and geological setting of obduction. Several questions will be addressed in this debate: the relationships and paradoxes between the nature of ophiolites, their geodynamic environment of formation, their geochemistry, their modality of obduction and ultimately the mountain range style where they are found.

Scaled centrifugal compressor, collector and running gear program

NASA Technical Reports Server (NTRS)

Kenehan, J. G.

1983-01-01

The Scaled Centrifugal Compressor, Collector and Running gear Program was conducted in support of an overall NASA strategy to improve small-compressor performance, durability, and reliability while reducing initial and life-cycle costs. Accordingly, Garrett designed and provided a test rig, gearbox coupling, and facility collector for a new NASA facility, and provided a scaled model of an existing, high-performance impeller for evaluation scaling effects on aerodynamic performance and for obtaining other performance data. Test-rig shafting was designed to operate smoothly throughout a speed range up to 60,000 rpm. Pressurized components were designed to operate at pressures up to 300 psia and at temperatures to 1000 F. Nonrotating components were designed to provide a margin-of-safety of 0.05 or greater; rotating components, for a margin-of-safety based on allowable yield and ultimate strengths. Design activities were supported by complete design analysis, and the finished hardware was subjected to check-runs to confirm proper operation. The test rig will support a wide range of compressor tests and evaluations.

Marginalizing Women: Images of Pregnancy in Williams Obstetrics

PubMed Central

Smith, Sheila A.; Condit, Deirdre M.

2000-01-01

This research analyzes the historical development of the medical construction of the pregnant body in 17 of 20 editions of Williams Obstetrics, an obstetrical textbook published continually from 1904 to 1997. Examination of the visual imagery of these works produced three key findings. First, depictions of the healthy or “normal” pregnant body are virtually absent throughout the series. Second, visual depictions of women's full bodies adhere to a race-based hierarchy of presentation. Finally, the fundamental discourse about pregnant and female bodies communicated to physicians (primarily) by these images is one of pathology and fragmentation. We conclude that the resulting social and medical construction of the pregnant and female body presented in the Williams series is one of disembodiment, abjection, and ultimately marginality. These findings support recent feminist research that criticizes both the increasing erasure of the person of the women from the medical interpretation of pregnancy and the concomitant decrease in women's perceived sense of empowerment as pregnant beings. PMID:17273202

How does continental lithosphere break-apart? A 3D seismic view on the transition from magma-poor rifted margin to magmatic oceanic lithosphere

NASA Astrophysics Data System (ADS)

Emmanuel, M.; Lescanne, M.; Picazo, S.; Tomasi, S.

2017-12-01

In the last decade, high-quality seismic data and drilling results drastically challenged our ideas about how continents break apart. New models address their observed variability and are presently redefining basics of rifting as well as exploration potential along deepwater rifted margins. Seafloor spreading is even more constrained by decades of scientific exploration along Mid Oceanic Ridges. By contrast, the transition between rifting and drifting remains a debated subject. This lithospheric breakup "event" is geologically recorded along Ocean-Continent Transitions (OCT) at the most distal part of margins before indubitable oceanic crust. Often lying along ultra-deepwater margin domains and buried beneath a thick sedimentary pile, high-quality images of these domains are rare but mandatory to get strong insights on the processes responsible for lithospheric break up and what are the consequences for the overlying basins. We intend to answer these questions by studying a world-class 3D seismic survey in a segment of a rifted margin exposed in the Atlantic. Through these data, we can show in details the OCT architecture between a magma-poor hyper-extended margin (with exhumed mantle) and a classical layered oceanic crust. It is characterized by 1- the development of out-of-sequence detachment systems with a landward-dipping geometry and 2- the increasing magmatic additions oceanwards (intrusives and extrusives). Geometry of these faults suggests that they may be decoupled at a mantle brittle-ductile interface what may be an indicator on thermicity. Furthermore, magmatism increases as deformation migrates to the future first indubitable oceanic crust what controls a progressive magmatic crustal thickening below, above and across a tapering rest of margin. As the magmatic budget increases oceanwards, full-rate divergence is less and less accommodated by faulting. Magmatic-sedimentary architectures of OCT is therefore changing from supra-detachment to magmatic oceanic half-grabens (low-crustal extension, high magma additions) and to ultimate layered oceanic crust (quasi-none crustal extension, full magmatic accretion). All of these elements suggest that lithospheric breakup can be addressed as a tectonic-magma competition as the brittle-ductile mantle interface is shallowing along OCT.

Translational applications of evaluating physiologic variability in human endotoxemia

PubMed Central

Scheff, Jeremy D.; Mavroudis, Panteleimon D.; Calvano, Steve E.; Androulakis, Ioannis P.

2012-01-01

Dysregulation of the inflammatory response is a critical component of many clinically challenging disorders such as sepsis. Inflammation is a biological process designed to lead to healing and recovery, ultimately restoring homeostasis; however, the failure to fully achieve those beneficial results can leave a patient in a dangerous persistent inflammatory state. One of the primary challenges in developing novel therapies in this area is that inflammation is comprised of a complex network of interacting pathways. Here, we discuss our approaches towards addressing this problem through computational systems biology, with a particular focus on how the presence of biological rhythms and the disruption of these rhythms in inflammation may be applied in a translational context. By leveraging the information content embedded in physiologic variability, ranging in scale from oscillations in autonomic activity driving short-term heart rate variability (HRV) to circadian rhythms in immunomodulatory hormones, there is significant potential to gain insight into the underlying physiology. PMID:23203205

Knowledge Translation in Rehabilitation: A Shared Vision.

PubMed

Moore, Jennifer L; Shikako-Thomas, Keiko; Backus, Deborah

2017-07-01

Advances in rehabilitation provide the infrastructure for research and clinical data to improve care and patient outcomes. However, gaps between research and practice are prevalent. Knowledge translation (KT) aims to decrease the gap between research and its clinical use. This special communication summarizes KT-related proceedings from the 2016 IV STEP conference, describes current KT in rehabilitation science, and provides suggestions for its application in clinical care. We propose a vision for rehabilitation clinical practice and research that includes the development, adaptation, and implementation of evidence-based practice recommendations, which will contribute to a learning health care system. A clinical research culture that supports this vision and methods to engage key stakeholders to innovate rehabilitation science and practice are described. Through implementation of this vision, we can lead an evolution in rehabilitation practice to ultimately prevent disabilities, predict better outcomes, exploit plasticity, and promote participation.

Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription

PubMed Central

Aguilar-Arnal, Lorena; Sassone-Corsi, Paolo

2015-01-01

Circadian rhythms drive the temporal organization of a wide variety of physiological and behavioral functions in ∼24-h cycles. This control is achieved through a complex program of gene expression. In mammals, the molecular clock machinery consists of interconnected transcriptional–translational feedback loops that ultimately ensure the proper oscillation of thousands of genes in a tissue-specific manner. To achieve circadian transcriptional control, chromatin remodelers serve the clock machinery by providing appropriate oscillations to the epigenome. Recent findings have revealed the presence of circadian interactomes, nuclear “hubs” of genome topology where coordinately expressed circadian genes physically interact in a spatial and temporal-specific manner. Thus, a circadian nuclear landscape seems to exist, whose interplay with metabolic pathways and clock regulators translates into specific transcriptional programs. Deciphering the molecular mechanisms that connect the circadian clock machinery with the nuclear landscape will reveal yet unexplored pathways that link cellular metabolism to epigenetic control. PMID:25378702

Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

PubMed Central

Smits, Paulien; Smeitink, Jan; van den Heuvel, Lambert

2010-01-01

Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders. PMID:20396601

Multiperspective smFRET reveals rate-determining late intermediates of ribosomal translocation.

PubMed

Wasserman, Michael R; Alejo, Jose L; Altman, Roger B; Blanchard, Scott C

2016-04-01

Directional translocation of the ribosome through the mRNA open reading frame is a critical determinant of translational fidelity. This process entails a complex interplay of large-scale conformational changes within the actively translating particle, which together coordinate the movement of tRNA and mRNA substrates with respect to the large and small ribosomal subunits. Using pre-steady state, single-molecule fluorescence resonance energy transfer imaging, we tracked the nature and timing of these conformational events within the Escherichia coli ribosome from five structural perspectives. Our investigations revealed direct evidence of structurally and kinetically distinct late intermediates during substrate movement, whose resolution determines the rate of translocation. These steps involve intramolecular events within the EF-G-GDP-bound ribosome, including exaggerated, reversible fluctuations of the small-subunit head domain, which ultimately facilitate peptidyl-tRNA's movement into its final post-translocation position.

Multi-perspective smFRET reveals rate-determining late intermediates of ribosomal translocation

PubMed Central

Wasserman, Michael R.; Alejo, Jose L.; Altman, Roger B.; Blanchard, Scott C.

2016-01-01

Directional translocation of the ribosome through the messenger RNA open reading frame is a critical determinant of translational fidelity. This process entails a complex interplay of large-scale conformational changes within the actively translating particle, which together coordinate the movement of transfer and messenger RNA substrates with respect to the large and small ribosomal subunits. Using pre-steady state, single-molecule fluorescence resonance energy transfer imaging, we have tracked the nature and timing of these conformational events within the Escherichia coli ribosome from five structural perspectives. Our investigations reveal direct evidence of structurally and kinetically distinct, late intermediates during substrate movement, whose resolution is rate-determining to the translocation mechanism. These steps involve intra-molecular events within the EFG(GDP)-bound ribosome, including exaggerated, reversible fluctuations of the small subunit head domain, which ultimately facilitate peptidyl-tRNA’s movement into its final post-translocation position. PMID:26926435

Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative.

PubMed

Straus, Sharon E; Brouwers, Melissa; Johnson, David; Lavis, John N; Légaré, France; Majumdar, Sumit R; McKibbon, K Ann; Sales, Anne E; Stacey, Dawn; Klein, Gail; Grimshaw, Jeremy

2011-12-09

Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT) and the resulting need to build capacity in both the science and practice of KT. We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date. We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.

Core competencies in the science and practice of knowledge translation: description of a Canadian strategic training initiative

PubMed Central

2011-01-01

Background Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT) and the resulting need to build capacity in both the science and practice of KT. Findings We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date. Conclusions We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system. PMID:22152223

Diego and Giorgina Vergani: The two hearts of translational autoimmunity.

PubMed

Liberal, Rodrigo; Selmi, Carlo; Gershwin, M Eric

2016-01-01

Since the publication of the first textbook on autoimmune diseases in 1963, the knowledge in the field has exponentially grown into numerous tracks of research, particularly at benchside. Systemic and organ-specific autoimmune diseases, as in the case of the liver, have witnessed notable advances in terms of epidemiology, genetics, effector and regulatory mechanisms, and ultimately treatment. While the available tools for communication have provided accelerating progress rates, we recognize that key opinion leaders continue to provide significant contributions to the field. The present issue is dedicated to celebrate Giorgina Mieli-Vergani and Diego Vergani as two of the finest examples of excellence in autoimmune liver diseases and the broader field of autoimmunity. Diego and Giorgina are extremely well-liked Colleagues who fully represent the translational efforts between laboratory research and clinically relevant questions in the practice of pediatric liver diseases and autoimmune hepatitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Valencia trough and the origin of the western Mediterranean basins

NASA Astrophysics Data System (ADS)

Vegas, R.

1992-03-01

Evolutionary models for the Valencia trough must be necessarily related to the Neogene-Present geodynamics of the western Mediterranean basins. All these basins occupy new space created in the wake of the westward translation of the Alboran block and the counter-clockwise rotation of the Corso-Sardinian block. This escape-tectonics, microplate dispersal, model can account for the co-existence and progressive migration of compressional and extensional strain fields within the Africa-Europe broad zone of convergence. In this escape-tectonics model, the Valencia trough has resulted in a complex evolution which includes: (1) latest Oligocene-Early Miocene rifting along the Catalan-Valencian margin due to the opening of the Gulf of Lions; (2) almost simultaneous, Early Miocene, transpressive thrusting in the Balearic margin related to the initiation of displacement of the Alboran block; and (3) Late Miocene generalized extension as a consequence of the opening of the South Balearic basin.

WE-AB-207B-03: A Computational Methodology for Determination of CTV-To-PTV Margins with Inter Fractional Shape Variations Based On a Statistical Point Distribution Model for Prostate Cancer Radiation Therapy

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

Shibayama, Y; Umezu, Y; Nakamura, Y

2016-06-15

Purpose: Our assumption was that interfractional shape variations of target volumes could not be negligible for determination of clinical target volume (CTV)-to-planning target volume (PTV) margins. The aim of this study was to investigate this assumption as a simulation study by developing a computational framework of CTV-to-PTV margins with taking the interfractional shape variations into account based on point distribution model (PDM) Methods: The systematic and random errors for interfractional shape variations and translations of target volumes were evaluated for four types of CTV regions (only a prostate, a prostate plus proximal 1-cm seminal vesicles, a prostate plus proximal 2-cmmore » seminal vesicles, and a prostate plus whole seminal vesicles). The CTV regions were delineated depending on prostate cancer risk groups on planning computed tomography (CT) and cone beam CT (CBCT) images of 73 fractions of 10 patients. The random and systematic errors for shape variations of CTV regions were derived from PDMs of CTV surfaces for all fractions of each patient. Systematic errors of shape variations of CTV regions were derived by comparing PDMs between planning CTV surfaces and average CTV surfaces. Finally, anisotropic CTV-to-PTV margins with shape variations in 6 directions (anterior, posterior, superior, inferior, right, and left) were computed by using a van Herk margin formula. Results: Differences between CTV-to-PTV margins with and without shape variations ranged from 0.7 to 1.7 mm in anterior direction, 1.0 to 2.8 mm in posterior direction, 0.8 to 2.8 mm in superior direction, 0.6 to 1.6 mm in inferior direction, 1.4 to 4.4 mm in right direction, and 1.3 to 5.2 mm in left direction. Conclusion: More than 1.0 mm additional margins were needed at least in 3 directions to guarantee CTV coverage due to shape variations. Therefore, shape variations should be taken into account for the determination of CTV-to-PTV margins.« less

Evaluation metrics for biostatistical and epidemiological collaborations.

PubMed

Rubio, Doris McGartland; Del Junco, Deborah J; Bhore, Rafia; Lindsell, Christopher J; Oster, Robert A; Wittkowski, Knut M; Welty, Leah J; Li, Yi-Ju; Demets, Dave

2011-10-15

Increasing demands for evidence-based medicine and for the translation of biomedical research into individual and public health benefit have been accompanied by the proliferation of special units that offer expertise in biostatistics, epidemiology, and research design (BERD) within academic health centers. Objective metrics that can be used to evaluate, track, and improve the performance of these BERD units are critical to their successful establishment and sustainable future. To develop a set of reliable but versatile metrics that can be adapted easily to different environments and evolving needs, we consulted with members of BERD units from the consortium of academic health centers funded by the Clinical and Translational Science Award Program of the National Institutes of Health. Through a systematic process of consensus building and document drafting, we formulated metrics that covered the three identified domains of BERD practices: the development and maintenance of collaborations with clinical and translational science investigators, the application of BERD-related methods to clinical and translational research, and the discovery of novel BERD-related methodologies. In this article, we describe the set of metrics and advocate their use for evaluating BERD practices. The routine application, comparison of findings across diverse BERD units, and ongoing refinement of the metrics will identify trends, facilitate meaningful changes, and ultimately enhance the contribution of BERD activities to biomedical research. Copyright © 2011 John Wiley & Sons, Ltd.

Excited-state dissociation dynamics of phenol studied by a new time-resolved technique

NASA Astrophysics Data System (ADS)

Lin, Yen-Cheng; Lee, Chin; Lee, Shih-Huang; Lee, Yin-Yu; Lee, Yuan T.; Tseng, Chien-Ming; Ni, Chi-Kung

2018-02-01

Phenol is an important model molecule for the theoretical and experimental investigation of dissociation in the multistate potential energy surfaces. Recent theoretical calculations [X. Xu et al., J. Am. Chem. Soc. 136, 16378 (2014)] suggest that the phenoxyl radical produced in both the X and A states from the O-H bond fission in phenol can contribute substantially to the slow component of photofragment translational energy distribution. However, current experimental techniques struggle to separate the contributions from different dissociation pathways. A new type of time-resolved pump-probe experiment is described that enables the selection of the products generated from a specific time window after molecules are excited by a pump laser pulse and can quantitatively characterize the translational energy distribution and branching ratio of each dissociation pathway. This method modifies conventional photofragment translational spectroscopy by reducing the acceptance angles of the detection region and changing the interaction region of the pump laser beam and the molecular beam along the molecular beam axis. The translational energy distributions and branching ratios of the phenoxyl radicals produced in the X, A, and B states from the photodissociation of phenol at 213 and 193 nm are reported. Unlike other techniques, this method has no interference from the undissociated hot molecules. It can ultimately become a standard pump-probe technique for the study of large molecule photodissociation in multistates.

Understanding Recent Mass Balance Changes of the Greenland Ice Sheet

NASA Technical Reports Server (NTRS)

vanderVeen, Cornelius

2003-01-01

The ultimate goal of this project is to better understand the current transfer of mass between the Greenland Ice Sheet, the world's oceans and the atmosphere, and to identify processes controlling the rate of this transfer, to be able to predict with greater confidence future contributions to global sea level rise. During the first year of this project, we focused on establishing longer-term records of change of selected outlet glaciers, reevaluation of mass input to the ice sheet and analysis of climate records derived from ice cores, and modeling meltwater production and runoff from the margins of the ice sheet.

Enhanced open ocean storage of CO2 from shelf sea pumping.

PubMed

Thomas, Helmuth; Bozec, Yann; Elkalay, Khalid; de Baar, Hein J W

2004-05-14

Seasonal field observations show that the North Sea, a Northern European shelf sea, is highly efficient in pumping carbon dioxide from the atmosphere to the North Atlantic Ocean. The bottom topography-controlled stratification separates production and respiration processes in the North Sea, causing a carbon dioxide increase in the subsurface layer that is ultimately exported to the North Atlantic Ocean. Globally extrapolated, the net uptake of carbon dioxide by coastal and marginal seas is about 20% of the world ocean's uptake of anthropogenic carbon dioxide, thus enhancing substantially the open ocean carbon dioxide storage.

A statistical overview of mass movement characteristics on the North American Atlantic outer continental margin

USGS Publications Warehouse

Booth, James S.; O'Leary, Dennis W.

1992-01-01

An analysis of 179 mass movements on the North American Atlantic continental slope and upper rise shows that slope failures have occurred throughout the geographic extent of the outer margin. Although the slope failures show no striking affinity for a particular depth as an origination level, there is a broad, primary mode centered at about 900 m. The resulting slides terminate at almost all depths and have a primary mode at 1100 m, but the slope/rise boundary (at 2200 m) also is an important mode. Slope failures have occurred at declivities ranging from 1° to 30° (typically, 4°); the resultant mass movement deposits vary in width from 0.2 to 50 km (typically, 1-2 km) and in length from 0.3 to 380 km (typically, 2–4 km), and they have been reported to be as thick as 650 m. On a numeric basis, mass movements are slightly more prevalent on open slopes than in other physiographic settings, and both translational and rotational failure surfaces are common. The typical mass movement is disintegrative in nature. Open slope slides tend to occur at lower slope angles and are larger than canyon slides. Further, large‐scale slides rather than small‐scale slides tend to originate on gentle slopes (≍ 3-4°). Rotational slope failures appear to have a slightly greater chance of occurring in canyons, but there is no analogous bias associated with translational failures. Similarly, disintegrative slides seem more likely to be associated with rotational slope failures than translational ones and are longer than their nondisintegrative counterparts. The occurrence of such a variety of mass movements at low declivities implies that a regional failure mechanism has prevailed. We suggest that earthquakes or, perhaps in some areas, gas hydrates are the most likely cause of the slope failures.

Use of the Stanford Brief Activity Survey for physical activity assessment in postpartum Latinas: a validation study of a linguistically translated Spanish version.

PubMed

Joseph, Rodney P; Ainsworth, Barbara E; Vega-López, Sonia; Keller, Colleen S

2014-01-01

This study assessed the concurrent validity of the English and a linguistic Spanish translation of the Stanford Brief Activity Survey (SBAS) with pedometer-measured physical activity (PA) among postpartum Latinas. Latinas (n 97) completed the SBAS in either English (n 47) or Spanish (n 50) and wore pedometers 7 days at three different assessment periods. The English version demonstrated significant trends (p .01) for differentiating aerobic walking steps (AWS) and aerobic walking time (AWT) across SBAS intensity categories at two of the three assessment periods. The Spanish version showed marginally significant trends for differentiating AWS (p .048) and AWT (p .052) across SBAS intensity categories at only one assessment period. The English version of the SBAS is effective in assessing PA status among Latinas; however, the Spanish version indicates a need for research to further explore cultural and linguistic adaptations of the SBAS.

The Pitt Innovation Challenge (PInCh): Driving Innovation in Translational Research Through an Incentive-Based, Problem-Focused Competition.

PubMed

Fitzpatrick, Nicole Edgar; Maier, John; Yasko, Laurel; Mathias, David; Qua, Kacy; Wagner, Erika; Miller, Elizabeth; Reis, Steven E

2017-05-01

Translational research aims to move scientific discoveries across the biomedical spectrum from the laboratory to humans, and to ultimately transform clinical practice and public health policies. Despite efforts to accelerate translational research through national initiatives, several major hurdles remain. The authors created the Pitt Innovation Challenge (PInCh) as an incentive-based, problem-focused approach to solving identified clinical or public health problems at the University of Pittsburgh Clinical and Translational Science Institute in spring 2014. With input from a broad range of stakeholders, PInCh leadership arrived at the challenge question: How do we empower individuals to take control of their own health outcomes? The authors developed the PInCh's three-round proposal submission and review process as well as an online contest management tool to support the process. Ninety-two teams submitted video proposals in round one. Proposals included mobile applications (29; 32%), other information technology (19; 21%), and community program (22; 24%) solutions. Ten teams advanced to the final round, where three were awarded $100,000 to implement their solution over 12 months. In a 6-month follow-up survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections outside their normal sphere of collaborators. Additional educational training sessions related to problem-focused research will be developed. The PInCh will be expanded to engage investment and industry communities to facilitate the translation of solutions to clinical practice via commercialization pathways. External organizations and other universities will be engaged to use the PInCh as a mechanism to fuel innovation in their spaces.

Computational Modeling and Analysis of Insulin Induced Eukaryotic Translation Initiation

PubMed Central

Lequieu, Joshua; Chakrabarti, Anirikh; Nayak, Satyaprakash; Varner, Jeffrey D.

2011-01-01

Insulin, the primary hormone regulating the level of glucose in the bloodstream, modulates a variety of cellular and enzymatic processes in normal and diseased cells. Insulin signals are processed by a complex network of biochemical interactions which ultimately induce gene expression programs or other processes such as translation initiation. Surprisingly, despite the wealth of literature on insulin signaling, the relative importance of the components linking insulin with translation initiation remains unclear. We addressed this question by developing and interrogating a family of mathematical models of insulin induced translation initiation. The insulin network was modeled using mass-action kinetics within an ordinary differential equation (ODE) framework. A family of model parameters was estimated, starting from an initial best fit parameter set, using 24 experimental data sets taken from literature. The residual between model simulations and each of the experimental constraints were simultaneously minimized using multiobjective optimization. Interrogation of the model population, using sensitivity and robustness analysis, identified an insulin-dependent switch that controlled translation initiation. Our analysis suggested that without insulin, a balance between the pro-initiation activity of the GTP-binding protein Rheb and anti-initiation activity of PTEN controlled basal initiation. On the other hand, in the presence of insulin a combination of PI3K and Rheb activity controlled inducible initiation, where PI3K was only critical in the presence of insulin. Other well known regulatory mechanisms governing insulin action, for example IRS-1 negative feedback, modulated the relative importance of PI3K and Rheb but did not fundamentally change the signal flow. PMID:22102801

A Comparison of Pathophysiology in Humans and Rodent Models of Subarachnoid Hemorrhage

PubMed Central

Leclerc, Jenna L.; Garcia, Joshua M.; Diller, Matthew A.; Carpenter, Anne-Marie; Kamat, Pradip K.; Hoh, Brian L.; Doré, Sylvain

2018-01-01

Non-traumatic subarachnoid hemorrhage (SAH) affects an estimated 30,000 people each year in the United States, with an overall mortality of ~30%. Most cases of SAH result from a ruptured intracranial aneurysm, require long hospital stays, and result in significant disability and high fatality. Early brain injury (EBI) and delayed cerebral vasospasm (CV) have been implicated as leading causes of morbidity and mortality in these patients, necessitating intense focus on developing preclinical animal models that replicate clinical SAH complete with delayed CV. Despite the variety of animal models currently available, translation of findings from rodent models to clinical trials has proven especially difficult. While the explanation for this lack of translation is unclear, possibilities include the lack of standardized practices and poor replication of human pathophysiology, such as delayed cerebral vasospasm and ischemia, in rodent models of SAH. In this review, we summarize the different approaches to simulating SAH in rodents, in particular elucidating the key pathophysiology of the various methods and models. Ultimately, we suggest the development of standardized model of rodent SAH that better replicates human pathophysiology for moving forward with translational research. PMID:29623028

Future Directions for Research in Autism Spectrum Disorders

PubMed Central

Damiano, Cara R.; Mazefsky, Carla A.; White, Susan W.; Dichter, Gabriel S.

2014-01-01

This article suggests future directions for research aimed at improved understanding of the etiology and pathophysiology of autism spectrum disorder (ASD) as well as pharmacologic and psychosocial interventions for ASD across the lifespan. The past few years have witnessed unprecedented transformations in the understanding of ASD neurobiology, genetics, early identification, and early intervention. However, recent increases in ASD prevalence estimates highlight the urgent need for continued efforts to translate novel ASD discoveries into effective interventions for all individuals with ASD. In this article we highlight promising areas for ongoing and new research expected to quicken the pace of scientific discovery and ultimately the translation of research findings into accessible and empirically supported interventions for those with ASD. We highlight emerging research in the following domains as particularly promising and pressing: (1) preclinical models; (2) experimental therapeutics; (3) early identification and intervention; (4) psychiatric comorbidities and the Research Domain Criteria (RDoC) initiative; (5) ecological momentary assessment; (6) neurotechnologies; and (7) the needs of adults with ASD. Increased research emphasis in these areas has the potential to hasten the translation of knowledge on the etiological mechanisms of ASD to psychosocial and biological interventions to reduce the burden of ASD on affected individuals and their families. PMID:25216048

Towards programming languages for genetic engineering of living cells

PubMed Central

Pedersen, Michael; Phillips, Andrew

2009-01-01

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts. PMID:19369220

Imaging Atherosclerosis

PubMed Central

Tarkin, Jason M.; Dweck, Marc R.; Evans, Nicholas R.; Takx, Richard A.P.; Brown, Adam J.; Tawakol, Ahmed; Fayad, Zahi A.

2016-01-01

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID:26892971

Towards programming languages for genetic engineering of living cells.

PubMed

Pedersen, Michael; Phillips, Andrew

2009-08-06

Synthetic biology aims at producing novel biological systems to carry out some desired and well-defined functions. An ultimate dream is to design these systems at a high level of abstraction using engineering-based tools and programming languages, press a button, and have the design translated to DNA sequences that can be synthesized and put to work in living cells. We introduce such a programming language, which allows logical interactions between potentially undetermined proteins and genes to be expressed in a modular manner. Programs can be translated by a compiler into sequences of standard biological parts, a process that relies on logic programming and prototype databases that contain known biological parts and protein interactions. Programs can also be translated to reactions, allowing simulations to be carried out. While current limitations on available data prevent full use of the language in practical applications, the language can be used to develop formal models of synthetic systems, which are otherwise often presented by informal notations. The language can also serve as a concrete proposal on which future language designs can be discussed, and can help to guide the emerging standard of biological parts which so far has focused on biological, rather than logical, properties of parts.

Novel applications of near-infrared fluorescence imaging in orthopaedic surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Henderson, Eric R.; DSouza, Alisha V.; Paulsen, Keith D.; Pogue, Brian W.

2017-02-01

Sarcomas are cancers of the bones, muscles, nerves, and fat that require complete surgical removal for cure. The primary surgical goal therefore is to remove the tumor with a zone of normal, non-cancerous tissue surrounding the tumor, considered a `negative' surgical margin. At present, surgeons rely on radiologic imaging and visual and tactile clues to gauge cancer depth and guide surgical excision. This can result in removal of too much or too little tissue, which can lead to unnecessary removal of vital structures or incomplete cancer removal, respectively. Both results can have negative effects on ultimate patient outcome, with positive margins reported in 23% of sarcoma surgeries. Near-infrared (NIR) fluorescence probes are molecules that when stimulated with specific, known frequencies of near-infrared light will emit light of another distinct frequency. NIR light penetrates human tissue reasonably well and therefore can be used to detect the presence and location of unseen structures labeled with NIR fluorescence probes through several centimeters of tissue. Intra-operative near-infrared (NIR) fluorescence probes have been effective for this purpose in brain tumor surgery and may be applicable to sarcoma surgery. Foundational research is needed to explore the potential of this affibody probe and perfusion probes to estimate margin thickness in sarcoma surgery. In this study we will determine if sarcoma labeling using NIR fluorescence probes is superior with perfusion probes or a novel affibody probe. We will also determine whether NIR fluorescence using perfusion probes or a novel affibody probe can be correlated accurately to margin thickness.

Defining and addressing moral distress: tools for critical care nursing leaders.

PubMed

Rushton, Cynda Hylton

2006-01-01

Nurse clinicians may experience moral distress when they are unable to translate their moral choices into moral action. The costs of unrelieved moral distress are high; ultimately, as with all unresolved professional conflicts, the quality of patient care suffers. As a systematic process for change, this article offers the AACN's Model to Rise Above Moral Distress, describing four A's: ask, affirm, assess, and act. To help critical care nurses working to address moral distress, the article identifies 11 action steps they can take to develop an ethical practice environment.

Elucidation of the genome organization of tobacco mosaic virus.

PubMed Central

Zaitlin, M

1999-01-01

Proteins unique to tobacco mosaic virus (TMV)-infected plants were detected in the 1970s by electrophoretic analyses of extracts of virus-infected tissues, comparing their proteins to those generated in extracts of uninfected tissues. The genome organization of TMV was deduced principally from studies involving in vitro translation of proteins from the genomic and subgenomic messenger RNAs. The ultimate analysis of the TMV genome came in 1982 when P. Goelet and colleagues sequenced the entire genome. Studies leading to the elucidation of the TMV genome organization are described below. PMID:10212938

An Image-Guided Study of Setup Reproducibility of Postmastectomy Breast Cancer Patients Treated With Inverse-Planned Intensity Modulated Radiation Therapy

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

Feng, Christine H.; Gerry, Emily; Chmura, Steven J.

2015-01-01

Purpose: To calculate planning target volume (PTV) margins for chest wall and regional nodal targets using daily orthogonal kilovolt (kV) imaging and to study residual setup error after kV alignment using volumetric cone-beam computed tomography (CBCT). Methods and Materials: Twenty-one postmastectomy patients were treated with intensity modulated radiation therapy with 7-mm PTV margins. Population-based PTV margins were calculated from translational shifts after daily kV positioning and/or weekly CBCT data for each of 8 patients, whose surgical clips were used as surrogates for target volumes. Errors from kV and CBCT data were mathematically combined to generate PTV margins for 3 simulatedmore » alignment workflows: (1) skin marks alone; (2) weekly kV imaging; and (3) daily kV imaging. Results: The kV data from 613 treatment fractions indicated that a 7-mm uniform margin would account for 95% of daily shifts if patients were positioned using only skin marks. Total setup errors incorporating both kV and CBCT data were larger than those from kV alone, yielding PTV expansions of 7 mm anterior–posterior, 9 mm left–right, and 9 mm superior–inferior. Required PTV margins after weekly kV imaging were similar in magnitude as alignment to skin marks, but rotational adjustments of patients were required in 32% ± 17% of treatments. These rotations would have remained uncorrected without the use of daily kV imaging. Despite the use of daily kV imaging, CBCT data taken at the treatment position indicate that an anisotropic PTV margin of 6 mm anterior–posterior, 4 mm left–right, and 8 mm superior–inferior must be retained to account for residual errors. Conclusions: Cone-beam CT provides additional information on 3-dimensional reproducibility of treatment setup for chest wall targets. Three-dimensional data indicate that a uniform 7-mm PTV margin is insufficient in the absence of daily IGRT. Interfraction movement is greater than suggested by 2-dimensional imaging, thus a margin of at least 4 to 8 mm must be retained despite the use of daily IGRT.« less

Conduit margin heating and deformation during the AD 1886 basaltic Plinian eruption at Tarawera volcano, New Zealand.

PubMed

Schauroth, Jenny; Wadsworth, Fabian B; Kennedy, Ben; von Aulock, Felix W; Lavallée, Yan; Damby, David E; Vasseur, Jérémie; Scheu, Bettina; Dingwell, Donald B

During explosive eruptions, a suspension of gas and pyroclasts rises rapidly within a conduit. Here, we have analysed textures preserved in the walls of a pyroclastic feeder dyke of the AD 1886 Tarawera basaltic Plinian fissure eruption. The samples examined consist of basaltic ash and scoria plastered onto a conduit wall of a coherent rhyolite dome and a welded rhyolitic dome breccia. We examine the textural evidence for the response of the wall material, built of ∼75 vol.% glass and ∼25 vol.% crystals (pore-free equivalent), to mass movement in the adjacent conduit. In the rhyolitic wall material, we quantify the orientation and aspect ratio of biotite crystals as strain markers of simple shear deformation, and interpret juxtaposed regions of vesiculation and vesicle collapse as evidence of conduit wall heating. Systematic changes occur close to the margin: (1) porosity is highly variable, with areas locally vesiculated or densified, (2) biotite crystals are oriented with their long axis parallel to the margin, (3) the biotites have greater aspect ratios close to the margin and (4) the biotite crystals are fractured. We interpret the biotite phenocryst deformation to result from crystal fracture, rotation and cleavage-parallel bookcase translation. These textural observations are inferred to indicate mechanical coupling between the hot gas-ash jet and the conduit wall and reheating of wall rock rhyolite. We couple these observations with a simple 1D conductive heating model to show what minimum temperature the conduit wall needs to reach in order to achieve a temperature above the glass transition throughout the texturally-defined deformed zone. We propose that conduit wall heating and resulting deformation influences conduit margin outgassing and may enhance the intensity of such large basaltic eruptions.

Natural-gas hydrates: Resource of the twenty-first century?

USGS Publications Warehouse

Collett, T.S.

2001-01-01

Although considerable uncertainty and disagreement prevail concerning the world's gas-hydrate resources, the estimated amount of gas in those gas-hydrate accumulations greatly exceeds the volume of known conventional gas reserves. However, the role that gas hydrates will play in contributing to the world's energy requirements will ultimately depend less on the volume of gas-hydrate resources than on the cost to extract them. Gas hydrates occur in sedimentary deposits under conditions of pressure and temperature present in permafrost regions and beneath the sea in outer continental margins. The combined information from arctic gas-hydrate studies shows that in permafrost regions, gas hydrates may exist at subsurface depths ranging from about 130 m to 2000 m. The presence of gas hydrates in offshore continental margins has been inferred mainly from anomalous seismic reflectors (known as bottom-simulating reflectors) that have been mapped at depths below the seafloor ranging from approximately 100 m to 1100 m. Current estimates of the amount of gas in the world's marine and permafrost gas-hydrate accumulations are in rough accord at about 20,000 trillion m3. Gas hydrate as an energy commodity is often grouped with other unconventional hydrocarbon resources. In most cases, the evolution of a nonproducible unconventional resource to a producible energy resource has relied on significant capital investment and technology development. To evaluate the energy-resource potential of gas hydrates will also require the support of sustained research and development programs. Despite the fact that relatively little is known about the ultimate resource potential of gas hydrates, it is certain that they are a vast storehouse of natural gas, and significant technical challenges will need to be met before this enormous resource can be considered an economically producible reserve.

Marginalization and social change processes among lesbian, gay, bisexual and transgender persons in Swaziland: implications for HIV prevention.

PubMed

H Logie, Carmen; Perez-Brumer, Amaya; Jenkinson, Jesse; Madau, Veli; Nhlengethwa, Winnie; Baral, Stefan

2018-05-30

Swaziland has among the highest national adult HIV prevalence globally. There is limited knowledge of HIV vulnerabilities and prevention engagement among lesbian, gay, bisexual and transgender (LGBT) persons in the context of Swaziland's criminalization of consensual same-sex practices. This study explored social processes of marginalization to assess how they could potentiate HIV vulnerabilities and limit engagement in HIV prevention services. Additionally, we assessed positive change to better understand existing strategies employed by LGBT persons to challenge these HIV prevention barriers. Guided by community-based research methodology and conducted in Mbabane and Manzini, Swaziland, data were collected by LGBT peer-research assistants (PRA) in collaboration with an LGBT community organization in Manzini. Semi-structured interviews were conducted by trained PRAs and explored HIV prevention, including experiences of stigma and coping. Audio files were transcribed verbatim, translated to English, and analyzed using thematic techniques. Among participants (n = 51; mean age: 26.47, SD: 4.68), 40 self-identifed as gay or lesbian (78.4%), 11 bisexual (22.6%), and 12 (23.5%) identified as transgender. Findings highlighted three primary processes of marginalization and positive change in structural, community, and internal domains. First, structural marginalization, which included criminalization, healthcare discrimination, and a scarcity of LGBT tailored HIV prevention resources was challenged by grassroots networks created to access and share specific HIV resources with LGBT persons and the Ministry of Health. Second, community marginalization included stigma and multi-dimensional forms of violence, however, this was met with LGBT persons providing mutual peer support, including for accessing HIV testing services. Thirdly, internal marginalization comprised of self-stigma and associated sexual risk practices was contrasted with coping strategies focused on self-acceptance, stemming from social support and leading to healthcare utilization. Jointly, these findings can inform the implementation of community-based and rights affirming HIV prevention and care cascade strategies that improve coverage of services with LGBT persons in Swaziland.

The promise and perils of HDAC inhibitors in neurodegeneration

PubMed Central

Didonna, Alessandro; Opal, Puneet

2015-01-01

Histone deacetylases (HDACs) represent emerging therapeutic targets in the context of neurodegeneration. Indeed, pharmacologic inhibition of HDACs activity in the nervous system has shown beneficial effects in several preclinical models of neurological disorders. However, the translation of such therapeutic approach to clinics has been only marginally successful, mainly due to our still limited knowledge about HDACs physiological role particularly in neurons. Here, we review the potential benefits along with the risks of targeting HDACs in light of what we currently know about HDAC activity in the brain. PMID:25642438

Translational research in addiction: toward a framework for the development of novel therapeutics.

PubMed

Paterson, Neil E

2011-06-15

The development of novel substance use disorder (SUD) therapeutics is insufficient to meet the medical needs of a growing SUD patient population. The identification of translatable SUD models and tests is a crucial step in establishing a framework for SUD therapeutic development programs. The present review begins by identifying the clinical features of SUDs and highlights the narrow regulatory end-point required for approval of a novel SUD therapeutic. A conceptual overview of dependence is provided, followed by identification of potential intervention targets in the addiction cycle. The main components of the addiction cycle provide the framework for a discussion of preclinical models and their clinical analogs, all of which are focused on isolated behavioral end-points thought to be relevant to the persistence of compulsive drug use. Thus, the greatest obstacle to successful development is the gap between the multiplicity of preclinical and early clinical end-points and the regulatory end-point of sustained abstinence. This review proposes two pathways to bridging this gap: further development and validation of the preclinical extended access self-administration model; inclusion of secondary end-points comprising all of the measures highlighted in the present discussion in Phase 3 trials. Further, completion of the postdictive validation of analogous preclinical and clinical assays is of high priority. Ultimately, demonstration of the relevance and validity of a variety of end-points to the ultimate goal of abstinence will allow researchers to identify truly relevant therapeutic mechanisms and intervention targets, and establish a framework for SUD therapeutic development that allows optimal decision-making and resource allocation. 2011 Elsevier Inc. All rights reserved.

The interaction of fungi with dendritic cells: implications for Th immunity and vaccination.

PubMed

Claudia, Montagnoli; Bacci, Angela; Silvia, Bozza; Gaziano, Roberta; Spreca, Antonio; Romani, Luigina

2002-09-01

Human beings are continuously exposed to fungi, yet they rarely get fungal diseases. The delicate balance between the host and these otherwise harmless pathogens may turn into a parasitic relationship, resulting in the development of severe infections. The ability to reversibly switch between unicellular and filamentous forms, all of which can be found in infected tissues, is thought to be important for virulence. Efficient responses to the different forms of fungi require different mechanisms of immunity. Dendritic cells (DC) are uniquely able at decoding the fungus-associated information and translating it in qualitatively different T helper (Th) immune responses, in vitro and in vivo. Myeloid DC phagocytosed yeasts and hyphae of Candida albicans and conidia and hyphae of Aspergillus fumigatus, both in vitro and in vivo. Phagocytosis occurred through distinct phagocytic morphologies, involving the engagement and cooperativity of distinct recognition receptors. However, receptor engagement and cooperativity were greatly modified by opsonization. The engagement of distinct receptors translated into disparate downstream signaling events, ultimately affecting cytokine production and costimulation. In vivo studies confirmed that the choice of receptor and mode of entry of fungi into DC was responsible for Th polarization and patterns of susceptibility or resistance to infection. Adoptive transfer of different types of DC activated protective, nonprotective and regulatory T cells, ultimately affecting the outcome of infection. The conclusions are that the selective exploitation of receptors and mode of entry into DC may determine the full range of host's immune relationships with fungi and have important implications in the design of vaccine-based strategies.

Ore grade decrease as life cycle impact indicator for metal scarcity: the case of copper.

PubMed

Vieira, Marisa D M; Goedkoop, Mark J; Storm, Per; Huijbregts, Mark A J

2012-12-04

In the life cycle assessment (LCA) of products, the increasing scarcity of metal resources is currently addressed in a preliminary way. Here, we propose a new method on the basis of global ore grade information to assess the importance of the extraction of metal resources in the life cycle of products. It is shown how characterization factors, reflecting the decrease in ore grade due to an increase in metal extraction, can be derived from cumulative ore grade-tonnage relationships. CFs were derived for three different types of copper deposits (porphyry, sediment-hosted, and volcanogenic massive sulfide). We tested the influence of the CF model (marginal vs average), mathematical distribution (loglogistic vs loglinear), and reserve estimate (ultimate reserve vs reserve base). For the marginal CFs, the statistical distribution choice and the estimate of the copper reserves introduce a difference of a factor of 1.0-5.0 and a factor of 1.2-1.7, respectively. For the average CFs, the differences are larger for these two choices, i.e. respectively a factor of 5.7-43 and a factor of 2.1-3.8. Comparing the marginal CFs with the average CFs, the differences are higher (a factor 1.7-94). This paper demonstrates that cumulative grade-tonnage relationships for metal extraction can be used in LCA to assess the relative importance of metal extractions.

MRI-guided Dose-escalated Salvage Radiotherapy for Bulky Bladder Neck Recurrence of Prostate Cancer

PubMed Central

Tyran, Marguerite; Steinberg, Michael L.; Holden, Stuart B; Cao, Minsong

2018-01-01

Nearly 30% of patients treated with radical prostatectomy for prostate cancer ultimately develop biochemical recurrences, and nearly a quarter of men with nonpalpable biochemical recurrences have gross local recurrences identified with magnetic resonance imaging (MRI). The only curative intervention for patients with recurrent disease after radical prostatectomy is salvage radiotherapy – this is particularly true for patients with gross local recurrences. Furthermore, even in patients with an incurable metastatic disease, a local recurrence can be the source of significant morbidity and should be addressed. Delivering a sufficient dose of radiation in the postoperative setting to control gross disease while minimizing toxicity poses a significant technical challenge. Because of the inherent uncertainty in the verification of gross disease positioning with standard onboard imaging technologies, large margins must be used. Larger margins, in turn, will lead to larger volumes of tissue receiving high doses of radiation, potentially increasing long-term toxicity. Herein, we present the case of a patient with a bulky gross recurrence (>40 cm3) at the bladder neck and synchronous metastatic disease who was referred for salvage radiotherapy after a multidisciplinary consensus recommendation to pursue local therapy for mitigating urinary morbidity from the bulky tumor. The case illustrates the utilization of MRI-guided radiotherapy to allow significant margin reduction, thereby facilitating the delivery of an escalated dose of radiotherapy to a bulky recurrence. PMID:29805929

Clinical and Translational Science Awards: can they increase the efficiency and speed of clinical and translational research?

PubMed

Heller, Caren; de Melo-Martín, Inmaculada

2009-04-01

Most agree that the recent decades-long boom in biomedical research discoveries has not had a sufficient effect on the public's health. To overcome some of the barriers to speeding clinical and translational (C/T) research, the National Institutes of Health has established the Institutional Clinical and Translational Science Award (CTSA). To explore whether the CTSA proposal addresses major C/T barriers and whether funded institutions offer adequate solutions, the authors reviewed the obstacles to C/T research described in the literature and examined the completeness of the solutions offered by the 12 initial CTSA awardees. Through an analysis of the literature, the authors categorized C/T barriers into three categories (research workforce, research operations, and organizational silos). They then analyzed each CTSA proposal regarding the types of programs offered to address these barriers. They found that, in general, institutions developed detailed programs to address research workforce and research operations barriers but had limited to no solutions for organizational silos. The authors suggest that differences in how barriers are addressed are consistent with the degree of control that CTSA centers have over these obstacles and solutions. They argue that although CTSA centers might have an important role in successfully addressing some of the barriers to C/T research, CTSA centers might ultimately have difficulties achieving their purported goal of facilitating and increasing the efficiency and speed of C/T research because of a lack of control over solutions to some important obstacles facing such research.

Translational models of lung disease.

PubMed

Mercer, Paul F; Abbott-Banner, Katharine; Adcock, Ian M; Knowles, Richard G

2015-02-01

The 2nd Cross Company Respiratory Symposium (CCRS), held in Horsham, U.K. in 2012, brought together representatives from across the pharmaceutical industry with expert academics, in the common interest of improving the design and translational predictiveness of in vivo models of respiratory disease. Organized by the respiratory representatives of the European Federation of Pharmaceutical Industries and Federations (EFPIA) group of companies involved in the EU-funded project (U-BIOPRED), the aim of the symposium was to identify state-of-the-art improvements in the utility and design of models of respiratory disease, with a view to improving their translational potential and reducing wasteful animal usage. The respiratory research and development community is responding to the challenge of improving translation in several ways: greater collaboration and open sharing of data, careful selection of the species, complexity and chronicity of the models, improved practices in preclinical research, continued refinement in models of respiratory diseases and their sub-types, greater understanding of the biology underlying human respiratory diseases and their sub-types, and finally greater use of human (and especially disease-relevant) cells, tissues and explants. The present review highlights these initiatives, combining lessons from the symposium and papers published in Clinical Science arising from the symposium, with critiques of the models currently used in the settings of asthma, idiopathic pulmonary fibrosis and COPD. The ultimate hope is that this will contribute to a more rational, efficient and sustainable development of a range of new treatments for respiratory diseases that continue to cause substantial morbidity and mortality across the world.

Metallogenesis and tectonics of the Russian Far East, Alaska, and the Canadian Cordillera

USGS Publications Warehouse

Nokleberg, Warren J.; Bundtzen, Thomas K.; Eremin, Roman A.; Ratkin, Vladimir V.; Dawson, Kenneth M.; Shpikerman, Vladimir I.; Goryachev, Nikolai A.; Byalobzhesky, Stanislav G.; Frolov, Yuri F.; Khanchuk, Alexander I.; Koch, Richard D.; Monger, James W.H.; Pozdeev, Anany I.; Rozenblum, Ilya S.; Rodionov, Sergey M.; Parfenov, Leonid M.; Scotese, Christopher R.; Sidorov, Anatoly A.

2005-01-01

The Proterozoic and Phanerozoic metallogenic and tectonic evolution of the Russian Far East, Alaska, and the Canadian Cordillera is recorded in the cratons, craton margins, and orogenic collages of the Circum-North Pacific mountain belts that separate the North Pacific from the eastern North Asian and western North American Cratons. The collages consist of tectonostratigraphic terranes and contained metallogenic belts, which are composed of fragments of igneous arcs, accretionary-wedge and subduction-zone complexes, passive continental margins, and cratons. The terranes are overlapped by continental-margin-arc and sedimentary-basin assemblages and contained metallogenic belts. The metallogenic and geologic history of terranes, overlap assemblages, cratons, and craton margins has been complicated by postaccretion dismemberment and translation during strike-slip faulting that occurred subparallel to continental margins. Seven processes overlapping in time were responsible for most of metallogenic and geologic complexities of the region (1) In the Early and Middle Proterozoic, marine sedimentary basins developed on major cratons and were the loci for ironstone (Superior Fe) deposits and sediment-hosted Cu deposits that occur along both the North Asia Craton and North American Craton Margin. (2) In the Late Proterozoic, Late Devonian, and Early Carboniferous, major periods of rifting occurred along the ancestral margins of present-day Northeast Asia and northwestern North America. The rifting resulted in fragmentation of each continent, and formation of cratonal and passive continental-margin terranes that eventually migrated and accreted to other sites along the evolving margins of the original or adjacent continents. The rifting also resulted in formation of various massive-sulfide metallogenic belts. (3) From about the late Paleozoic through the mid-Cretaceous, a succession of island arcs and contained igneous-arc-related metallogenic belts and tectonically paired subduction zones formed near continental margins. (4) From about mainly the mid-Cretaceous through the present, a succession of continental-margin igneous arcs (some extending offshore into island arcs) and contained metallogenic belts, and tectonically paired subduction zones formed along the continental margins. (5) From about the Jurassic to the present, oblique convergence and rotations caused orogen-parallel sinistral, and then dextral displacements within the plate margins of the Northeast Asian and North American Cratons. The oblique convergences and rotations resulted in the fragmentation, displacement, and duplication of formerly more continuous arcs, subduction zones, passive continental margins, and contained metallogenic belts. These fragments were subsequently accreted along the margins of the expanding continental margins. (6) From the Early Jurassic through Tertiary, movement of the upper continental plates toward subduction zones resulted in strong plate coupling and accretion of the former island arcs, subduction zones, and contained metallogenic belts to continental margins. In this region, the multiple arc accretions were accompanied and followed by crustal thickening, anatexis, metamorphism, formation of collision-related metallogenic belts, and uplift; this resulted in the substantial growth of the North Asian and North American continents. (7) In the middle and late Cenozoic, oblique to orthogonal convergence of the Pacific Plate with present-day Alaska and Northeast Asia resulted in formation of the present ring of volcanoes and contained metallogenic belts around the Circum-North Pacific. Oblique convergence between the Pacific Plate and Alaska also resulted in major dextral-slip faulting in interior and southern Alaska and along the western part of the Aleutian- Wrangell arc. Associated with dextral-slip faulting was crustal extrusion of terranes from western Alaska into the Bering Sea.

Evolutionary speed limited by water in arid Australia

PubMed Central

Goldie, Xavier; Gillman, Len; Crisp, Mike; Wright, Shane

2010-01-01

The covariation of biodiversity with climate is a fundamental pattern in nature. However, despite the ubiquity of this relationship, a consensus on the ultimate cause remains elusive. The evolutionary speed hypothesis posits direct mechanistic links between ambient temperature, the tempo of micro-evolution and, ultimately, species richness. Previous research has demonstrated faster rates of molecular evolution in warmer climates for a broad range of poikilothermic and homeothermic organisms, in both terrestrial and aquatic environments. In terrestrial systems, species richness increases with both temperature and water availability and the interaction of those terms: productivity. However, the influence of water availability as an independent variable on micro-evolutionary processes has not been examined previously. Here, using methodology that limits the potentially confounding role of cladogenetic and demographic processes, we report, to our knowledge, the first evidence that woody plants living in the arid Australian Outback are evolving more slowly than related species growing at similar latitudes in moist habitats on the mesic continental margins. These results support a modified evolutionary speed explanation for the relationship between the water-energy balance and plant diversity patterns. PMID:20410038

Evolutionary speed limited by water in arid Australia.

PubMed

Goldie, Xavier; Gillman, Len; Crisp, Mike; Wright, Shane

2010-09-07

The covariation of biodiversity with climate is a fundamental pattern in nature. However, despite the ubiquity of this relationship, a consensus on the ultimate cause remains elusive. The evolutionary speed hypothesis posits direct mechanistic links between ambient temperature, the tempo of micro-evolution and, ultimately, species richness. Previous research has demonstrated faster rates of molecular evolution in warmer climates for a broad range of poikilothermic and homeothermic organisms, in both terrestrial and aquatic environments. In terrestrial systems, species richness increases with both temperature and water availability and the interaction of those terms: productivity. However, the influence of water availability as an independent variable on micro-evolutionary processes has not been examined previously. Here, using methodology that limits the potentially confounding role of cladogenetic and demographic processes, we report, to our knowledge, the first evidence that woody plants living in the arid Australian Outback are evolving more slowly than related species growing at similar latitudes in moist habitats on the mesic continental margins. These results support a modified evolutionary speed explanation for the relationship between the water-energy balance and plant diversity patterns.

An isotopic perspective on growth and differentiation of Proterozoic orogenic crust: From subduction magmatism to cratonization

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

Johnson, Simon P.; Korhonen, Fawna J.; Kirkland, Christopher L.

The in situ chemical differentiation of continental crust ultimately leads to the long-term stability of the continents. This process, more commonly known as ‘cratonization’, is driven by deep crustal melting with the transfer of those melts to shallower regions resulting in a strongly chemically stratified crust, with a refractory, dehydrated lower portion overlain by a complementary enriched upper portion. Since the lower to mid portions of continental crust are rarely exposed, investigation of the cratonization process must be through indirect methods. In this study we use in situ Hf and O isotope compositions of both magmatic and inherited zircons frommore » several felsic magmatic suites in the Capricorn Orogen of Western Australia to highlight the differentiation history (i.e. cratonization) of this portion of late Archean to Proterozoic orogenic crust. The Capricorn Orogen shows a distinct tectonomagmatic history that evolves from an active continental margin through to intracratonic reworking, ultimately leading to thermally stable crust that responds similarly to the bounding Archean Pilbara and Yilgarn Cratons.« less

Achieving excellence in the management of accounts receivable.

PubMed

Ladewig, T L; Hecht, B A

1993-09-01

Recent changes in healthcare reimbursement rules and practices have made the task of accounts receivable management a particularly demanding one for most financial managers. One multihospital system, after pursuing numerous strategies to reduce its accounts receivable with only marginal levels of success, launched a systemwide initiative to share both the positive and the negative accounts receivable management experiences of each department at each hospital in the system with all patient accounting staff. The objective of the initiative was to use the lessons learned from those experiences to attain excellence in accounts receivable management throughout the system. The ultimate success of the initiative is detailed in the following article.

The Pitt Innovation Challenge (PInCh): Driving Innovation in Translational Research Through an Incentive-Based, Problem-Focused Competition

PubMed Central

Fitzpatrick, Nicole Edgar; Maier, John; Yasko, Laurel; Mathias, David; Qua, Kacy; Wagner, Erika; Miller, Elizabeth; Reis, Steven E.

2017-01-01

Problem Translational research aims to move scientific discoveries across the biomedical spectrum from the laboratory to humans, and to ultimately transform clinical practice and public health policies. Despite efforts to accelerate translational research through national initiatives, several major hurdles remain. Approach The authors created the Pitt Innovation Challenge (PInCh) as an incentive-based, problem-focused approach to solving identified clinical or public health problems at the University of Pittsburgh Clinical and Translational Science Institute in spring 2014. With input from a broad range of stakeholders, PInCh leadership arrived at the challenge question: How do we empower individuals to take control of their own health outcomes? The authors developed the PInCh’s three-round proposal submission and review process as well as an online contest management tool to support the process. Outcomes Ninety-two teams submitted videos proposals in round one. Proposals included mobile applications (29, 32%), other information technology (19, 21%), and community program (22, 24%) solutions. Ten teams advanced to the final round, where three were awarded $100,000 to implement their solution over twelve months. In a six-month follow-up survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections outside their normal sphere of collaborators. Next Steps Additional educational training sessions related to problem-focused research will be developed. The PInCh will be expanded to engage investment and industry communities to facilitate the translation of solutions to clinical practice via commercialization pathways. External organizations and other universities will be engaged to use the PInCh as a mechanism to fuel innovation in their spaces. PMID:27508341

Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome

PubMed Central

Bolinger, Cheryl; Boris-Lawrie, Kathleen

2009-01-01

Retroviruses have evolved multiple strategies to direct the synthesis of a complex proteome from a single primary transcript. Their mechanisms are modulated by a breadth of virus-host interactions, which are of significant fundamental interest because they ultimately affect the efficiency of virus replication and disease pathogenesis. Motifs located within the untranslated region (UTR) of the retroviral RNA have established roles in transcriptional trans-activation, RNA packaging, and genome reverse transcription; and a growing literature has revealed a necessary role of the UTR in modulating the efficiency of viral protein synthesis. Examples include a 5' UTR post-transcriptional control element (PCE), present in at least eight retroviruses, that interacts with cellular RNA helicase A to facilitate cap-dependent polyribosome association; and 3' UTR constitutive transport element (CTE) of Mason-Pfizer monkey virus that interacts with Tap/NXF1 and SR protein 9G8 to facilitate RNA export and translational utilization. By contrast, nuclear protein hnRNP E1 negatively modulates HIV-1 Gag, Env, and Rev protein synthesis. Alternative initiation strategies by ribosomal frameshifting and leaky scanning enable polycistronic translation of the cap-dependent viral transcript. Other studies posit cap-independent translation initiation by internal ribosome entry at structural features of the 5' UTR of selected retroviruses. The retroviral armamentarium also commands mechanisms to counter cellular post-transcriptional innate defenses, including protein kinase R, 2',5'-oligoadenylate synthetase and the small RNA pathway. This review will discuss recent and historically-recognized insights into retrovirus translational control. The expanding knowledge of retroviral post-transcriptional control is vital to understanding the biology of the retroviral proteome. In a broad perspective, each new insight offers a prospective target for antiviral therapy and strategic improvement of gene transfer vectors. PMID:19166625

mRNA-Selective Translation Induced by FSH in Primary Sertoli Cells

PubMed Central

Musnier, Astrid; León, Kelly; Morales, Julia; Reiter, Eric; Boulo, Thomas; Costache, Vlad; Vourc'h, Patrick; Heitzler, Domitille; Oulhen, Nathalie; Poupon, Anne; Boulben, Sandrine; Cormier, Patrick

2012-01-01

FSH is a key hormonal regulator of Sertoli cell secretory activity, required to optimize sperm production. To fulfil its biological function, FSH binds a G protein-coupled receptor, the FSH-R. The FSH-R-transduced signaling network ultimately leads to the transcription or down-regulation of numerous genes. In addition, recent evidence has suggested that FSH might also regulate protein translation. However, this point has never been demonstrated conclusively yet. Here we have addressed this issue in primary rat Sertoli cells endogenously expressing physiological levels of FSH-R. We observed that, within 90 min of stimulation, FSH not only enhanced overall protein synthesis in a mammalian target of rapamycin-dependent manner but also increased the recruitment of mRNA to polysomes. m7GTP pull-down experiments revealed the functional recruitment of mammalian target of rapamycin and p70 S6 kinase to the 5′cap, further supported by the enhanced phosphorylation of one of p70 S6 kinase targets, the eukaryotic initiation factor 4B. Importantly, the scaffolding eukaryotic initiation factor 4G was also recruited, whereas eukaryotic initiation factor 4E-binding protein, the eukaryotic initiation factor 4E generic inhibitor, appeared to play a minor role in translational regulations induced by FSH, in contrast to what is generally observed in response to anabolic factors. This particular regulation of the translational machinery by FSH stimulation might support mRNA-selective translation, as shown here by quantitative RT-PCR amplification of the c-fos and vascular endothelial growth factor mRNA but not of all FSH target mRNA, in polysomal fractions. These findings add a new level of complexity to FSH biological roles in its natural target cells, which has been underappreciated so far. PMID:22383463

Psychometric properties of the Spanish version of the Resilience Scale.

PubMed

Heilemann, MarySue V; Lee, Kathryn; Kury, Felix Salvador

2003-01-01

The purpose of this study is to test the reliability and validity of a Spanish translation of the Resilience Scale (RS), which was originally created in English by Wagnild and Young (1993). A team of bilingual, bicultural translators participated in the translation process to enhance the linguistic accuracy and cultural appropriateness of the Spanish translation. As part of the convenience sample of 315 women of Mexican descent who participated in the larger study, data from 147 women who preferred to read and write in Spanish were used in this analysis. The English version of the RS consists of a 17-item "Personal Competence" subscale and an 8-item "Acceptance of Self and Life" subscale for a total of 25 items. However, two items had low item-total loadings and were removed to form a modified 23-item RS. The exploratory principal components factor analysis, varimax rotation, and subsequent goodness of fit indices were ambivalent on whether a one or two-factor solution was appropriate, but the chi-square difference test clearly demonstrated that the two-factor solution of the Spanish version was more useful in explaining variance than a one-factor solution. Internal consistency reliability was estimated with Cronbach's alpha (alpha = 0.93) which was acceptable for the 23-item RS as well as its subscales. Construct validity was demonstrated by a significant positive correlation between resilience and life satisfaction (r = 0.36; p < 0.001), and a significant negative correlation between resilience and depressive symptoms (r = -0.29; p < 0.01). This analysis ultimately supports the appropriateness of the modified 23-item Spanish translation of the RS and its subscales in a sample of urban, low-income women of Mexican descent in the U.S.

Challenges to collaboration in school mental health and strategies for overcoming them.

PubMed

Weist, Mark D; Mellin, Elizabeth A; Chambers, Kerri L; Lever, Nancy A; Haber, Deborah; Blaber, Christine

2012-02-01

This article reviews challenges to collaboration in school mental health (SMH) and presents practical strategies for overcoming them. The importance of collaboration to the success of SMH programs is reviewed, with a particular focus on collaboration between school- and community-employed professionals. Challenges to effective collaboration between school- and community-employed professionals in SMH are considered. Strategies for overcoming challenges to effective collaboration are presented. Marginalization of the SMH agenda, limited interdisciplinary teamwork, restricted coordination mechanisms, confidentiality concerns, and resource and funding issues are key challenges to collaboration. Strategies targeted toward each of these challenges may help improve the effectiveness of SMH programs and ultimately student outcomes. Collaboration between school- and community-employed professionals is critical to the success of SMH programs. Despite its promise, the success of SMH programs can be jeopardized by ineffective collaboration between school- and community-employed professionals. Strategies to overcome marginalization, promote authentic interdisciplinary teamwork, build effective coordination mechanisms, protect student and family confidentiality, and promote policy change and resource enhancements should be addressed in SMH improvement planning. © 2012, American School Health Association.

The breakdown of the weakly-nonlinear regime for kinetic instabilities

NASA Astrophysics Data System (ADS)

Sanz-Orozco, David; Berk, Herbert; Wang, Ge

2017-10-01

The evolution of marginally-unstable waves that interact resonantly with populations of energetic particles is governed by a well-known cubic integro-differential equation for the mode amplitude. One of the outcomes predicted by the equation is the so-called ``explosive'' regime, where the amplitude grows indefinitely, eventually taking the equation outside of its domain of validity. Beyond this point, only full Vlasov simulations will accurately describe the evolution of the mode amplitude. In this work, we study the breakdown of the cubic equation in detail. We find that, while the cubic equation is still valid, the distribution function of the energetic particles locally flattens or ``folds'' in phase space. This feature is unexpected in view of the assumptions of the theory that are given in. We also derive fifth-order terms in the wave equation, which not only give us a more accurate description of the marginally-unstable modes, but they also allow us to predict the breakdown of the cubic equation. Our findings allow us to better understand the transition between weakly-nonlinear modes and the long-term chirping modes that ultimately emerge.

Max-margin weight learning for medical knowledge network.

PubMed

Jiang, Jingchi; Xie, Jing; Zhao, Chao; Su, Jia; Guan, Yi; Yu, Qiubin

2018-03-01

The application of medical knowledge strongly affects the performance of intelligent diagnosis, and method of learning the weights of medical knowledge plays a substantial role in probabilistic graphical models (PGMs). The purpose of this study is to investigate a discriminative weight-learning method based on a medical knowledge network (MKN). We propose a training model called the maximum margin medical knowledge network (M 3 KN), which is strictly derived for calculating the weight of medical knowledge. Using the definition of a reasonable margin, the weight learning can be transformed into a margin optimization problem. To solve the optimization problem, we adopt a sequential minimal optimization (SMO) algorithm and the clique property of a Markov network. Ultimately, M 3 KN not only incorporates the inference ability of PGMs but also deals with high-dimensional logic knowledge. The experimental results indicate that M 3 KN obtains a higher F-measure score than the maximum likelihood learning algorithm of MKN for both Chinese Electronic Medical Records (CEMRs) and Blood Examination Records (BERs). Furthermore, the proposed approach is obviously superior to some classical machine learning algorithms for medical diagnosis. To adequately manifest the importance of domain knowledge, we numerically verify that the diagnostic accuracy of M 3 KN is gradually improved as the number of learned CEMRs increase, which contain important medical knowledge. Our experimental results show that the proposed method performs reliably for learning the weights of medical knowledge. M 3 KN outperforms other existing methods by achieving an F-measure of 0.731 for CEMRs and 0.4538 for BERs. This further illustrates that M 3 KN can facilitate the investigations of intelligent healthcare. Copyright © 2018 Elsevier B.V. All rights reserved.

Accretion of the southern Banda arc to the Australian plate margin determined by Global Positioning System measurements

NASA Astrophysics Data System (ADS)

Genrich, Joachim F.; Bock, Yehuda; McCaffrey, Robert; Calais, Eric; Stevens, Colleen W.; Subarya, Cecep

1996-04-01

Global Positioning System geodetic measurements at thirteen locations in Indonesia and four in Australia reveal that the Australian continent has accreted the Banda island arc to its margin. Small relative velocities of five sites on west Java, south Kalimantan, Bali, and south Sulawesi define a rigid Sunda shelf that moves relative to northern Australia in a manner consistent with pole locations from NUVEL-1 Australia-Eurasia but at a rate that is about 7% slower. Block-like northward motion of the southern Banda arc toward the Sunda shelf at nearly the same rate as Australia suggests that the Timor trough is now inactive as a thrust. Little of the convergence of Australia with Eurasia is accommodated by strain within the Banda arc structure. Most of the convergence appears to occur as northward translation of the rigid arc with shortening on the Flores and Wetar thrusts and possibly on faults within the back arc basin.

In Silico Augmentation of the Drug Development Pipeline: Examples from the study of Acute Inflammation.

PubMed

An, Gary; Bartels, John; Vodovotz, Yoram

2011-03-01

The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high-throughput and -content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are utilized in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. In this article, we present a Translational Systems Biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism.

Systems Approaches to Biology and Disease Enable Translational Systems Medicine

PubMed Central

Hood, Leroy; Tian, Qiang

2012-01-01

The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate. In the foreseeable future, clinicians, medical researchers, and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information, e.g., whole genome sequences, molecular profiling of diseased tissues, and periodic multi-analyte blood testing of biomarker panels for disease and wellness. The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual. It will also entail proactive participation from all major stakeholders in the health care system. We are at the dawn of predictive, preventive, personalized, and participatory (P4) medicine, the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics, proteomics, nanofluidics, single-cell analysis, and computation strategies in a highly-orchestrated discipline we termed translational systems medicine. PMID:23084773

Some experiences and opportunities for big data in translational research.

PubMed

Chute, Christopher G; Ullman-Cullere, Mollie; Wood, Grant M; Lin, Simon M; He, Min; Pathak, Jyotishman

2013-10-01

Health care has become increasingly information intensive. The advent of genomic data, integrated into patient care, significantly accelerates the complexity and amount of clinical data. Translational research in the present day increasingly embraces new biomedical discovery in this data-intensive world, thus entering the domain of "big data." The Electronic Medical Records and Genomics consortium has taught us many lessons, while simultaneously advances in commodity computing methods enable the academic community to affordably manage and process big data. Although great promise can emerge from the adoption of big data methods and philosophy, the heterogeneity and complexity of clinical data, in particular, pose additional challenges for big data inferencing and clinical application. However, the ultimate comparability and consistency of heterogeneous clinical information sources can be enhanced by existing and emerging data standards, which promise to bring order to clinical data chaos. Meaningful Use data standards in particular have already simplified the task of identifying clinical phenotyping patterns in electronic health records.

Advances in Diagnosis and Treatment of Fetal Alcohol Spectrum Disorders

PubMed Central

Murawski, Nathen J.; Moore, Eileen M.; Thomas, Jennifer D.; Riley, Edward P.

2015-01-01

Prenatal alcohol exposure can cause a number of physical, behavioral, cognitive, and neural impairments, collectively known as fetal alcohol spectrum disorders (FASD). This article examines basic research that has been or could be translated into practical applications for the diagnosis or treatment of FASD. Diagnosing FASD continues to be a challenge, but advances are being made at both basic science and clinical levels. These include identification of biomarkers, recognition of subtle facial characteristics of exposure, and examination of the relation between face, brain, and behavior. Basic research also is pointing toward potential new interventions for FASD involving pharmacotherapies, nutritional therapies, and exercise interventions. Although researchers have assessed the majority of these treatments in animal models of FASD, a limited number of recent clinical studies exist. An assessment of this literature suggests that targeted interventions can improve some impairments resulting from developmental alcohol exposure. However, combining interventions may prove more efficacious. Ultimately, advances in basic and clinical sciences may translate to clinical care, improving both diagnosis and treatment. PMID:26259091

Bioprinting: an assessment based on manufacturing readiness levels.

PubMed

Wu, Changsheng; Wang, Ben; Zhang, Chuck; Wysk, Richard A; Chen, Yi-Wen

2017-05-01

Over the last decade, bioprinting has emerged as a promising technology in the fields of tissue engineering and regenerative medicine. With recent advances in additive manufacturing, bioprinting is poised to provide patient-specific therapies and new approaches for tissue and organ studies, drug discoveries and even food manufacturing. Manufacturing Readiness Level (MRL) is a method that has been applied to assess manufacturing maturity and to identify risks and gaps in technology-manufacturing transitions. Technology Readiness Level (TRL) is used to evaluate the maturity of a technology. This paper reviews recent advances in bioprinting following the MRL scheme and addresses corresponding MRL levels of engineering challenges and gaps associated with the translation of bioprinting from lab-bench experiments to ultimate full-scale manufacturing of tissues and organs. According to our step-by-step TRL and MRL assessment, after years of rigorous investigation by the biotechnology community, bioprinting is on the cusp of entering the translational phase where laboratory research practices can be scaled up into manufacturing products specifically designed for individual patients.

Translating Big Data into Smart Data for Veterinary Epidemiology.

PubMed

VanderWaal, Kimberly; Morrison, Robert B; Neuhauser, Claudia; Vilalta, Carles; Perez, Andres M

2017-01-01

The increasing availability and complexity of data has led to new opportunities and challenges in veterinary epidemiology around how to translate abundant, diverse, and rapidly growing "big" data into meaningful insights for animal health. Big data analytics are used to understand health risks and minimize the impact of adverse animal health issues through identifying high-risk populations, combining data or processes acting at multiple scales through epidemiological modeling approaches, and harnessing high velocity data to monitor animal health trends and detect emerging health threats. The advent of big data requires the incorporation of new skills into veterinary epidemiology training, including, for example, machine learning and coding, to prepare a new generation of scientists and practitioners to engage with big data. Establishing pipelines to analyze big data in near real-time is the next step for progressing from simply having "big data" to create "smart data," with the objective of improving understanding of health risks, effectiveness of management and policy decisions, and ultimately preventing or at least minimizing the impact of adverse animal health issues.

Nanoscale Rheology and Anisotropic Diffusion Using Single Gold Nanorod Probes

NASA Astrophysics Data System (ADS)

Molaei, Mehdi; Atefi, Ehsan; Crocker, John C.

2018-03-01

The complex rotational and translational Brownian motion of anisotropic particles depends on their shape and the viscoelasticity of their surroundings. Because of their strong optical scattering and chemical versatility, gold nanorods would seem to provide the ultimate probes of rheology at the nanoscale, but the suitably accurate orientational tracking required to compute rheology has not been demonstrated. Here we image single gold nanorods with a laser-illuminated dark-field microscope and use optical polarization to determine their three-dimensional orientation to better than one degree. We convert the rotational diffusion of single nanorods in viscoelastic polyethylene glycol solutions to rheology and obtain excellent agreement with bulk measurements. Extensions of earlier models of anisotropic translational diffusion to three dimensions and viscoelastic fluids give excellent agreement with the observed motion of single nanorods. We find that nanorod tracking provides a uniquely capable approach to microrheology and provides a powerful tool for probing nanoscale dynamics and structure in a range of soft materials.

The CTSA mandate: are we there yet?

PubMed

Sampselle, Carolyn M; Pienta, Kenneth J; Markel, Dorene S

2010-01-01

The ultimate aim of the National Institutes of Health Clinical and Translational Science Award (CTSA) initiative is to accelerate the movement of discoveries that can benefit human health into widespread public use. To accomplish this translational mandate, the contributions of multiple disciplines, such as dentistry, nursing, pharmacy, public health, biostatistics, epidemiology, and bioengineering, are required in addition to medicine. The research community is also mandated to establish new partnerships with organized patient communities and front line health care providers to assure the bidirectional flow of information in order that health priorities experienced by the community inform the research agenda. This article summarizes current clinical research directives, the experience of the University of Michigan faculty during the first 2 years of CTSA support, and recommendations to enhance the effectiveness of future CTSA as well as other interdisciplinary initiatives. While the manuscript focuses most closely on the CTSA Community Engagement mission, the challenges to interdisciplinarity and bidirectionality extend beyond the focus of community engagement.

Some experiences and opportunities for big data in translational research

PubMed Central

Chute, Christopher G.; Ullman-Cullere, Mollie; Wood, Grant M.; Lin, Simon M.; He, Min; Pathak, Jyotishman

2014-01-01

Health care has become increasingly information intensive. The advent of genomic data, integrated into patient care, significantly accelerates the complexity and amount of clinical data. Translational research in the present day increasingly embraces new biomedical discovery in this data-intensive world, thus entering the domain of “big data.” The Electronic Medical Records and Genomics consortium has taught us many lessons, while simultaneously advances in commodity computing methods enable the academic community to affordably manage and process big data. Although great promise can emerge from the adoption of big data methods and philosophy, the heterogeneity and complexity of clinical data, in particular, pose additional challenges for big data inferencing and clinical application. However, the ultimate comparability and consistency of heterogeneous clinical information sources can be enhanced by existing and emerging data standards, which promise to bring order to clinical data chaos. Meaningful Use data standards in particular have already simplified the task of identifying clinical phenotyping patterns in electronic health records. PMID:24008998

Margins of stability in young adults with traumatic transtibial amputation walking in destabilizing environments✫

PubMed Central

Beltran, Eduardo J.; Dingwell, Jonathan B.; Wilken, Jason M.

2014-01-01

Understanding how lower-limb amputation affects walking stability, specifically in destabilizing environments, is essential for developing effective interventions to prevent falls. This study quantified mediolateral margins of stability (MOS) and MOS sub-components in young individuals with traumatic unilateral transtibial amputation (TTA) and young able-bodied individuals (AB). Thirteen AB and nine TTA completed five 3-minute walking trials in a Computer Assisted Rehabilitation ENvironment (CAREN) system under three each of three test conditions: no perturbations, pseudo-random mediolateral translations of the platform, and pseudo-random mediolateral translations of the visual field. Compared to the unperturbed trials, TTA exhibited increased mean MOS and MOS variability during platform and visual field perturbations (p < 0.010). Also, AB exhibited increased mean MOS during visual field perturbations and increased MOS variability during both platform and visual field perturbations (p < 0.050). During platform perturbations, TTA exhibited significantly greater values than AB for mean MOS (p < 0.050) and MOS variability (p < 0.050); variability of the lateral distance between the center of mass (COM) and base of support at initial contact (p < 0.005); mean and variability of the range of COM motion (p < 0.010); and variability of COM peak velocity (p < 0.050). As determined by mean MOS and MOS variability, young and otherwise healthy individuals with transtibial amputation achieved stability similar to that of their able-bodied counterparts during unperturbed and visually-perturbed walking. However, based on mean and variability of MOS, unilateral transtibial amputation was shown to have affected walking stability during platform perturbations. PMID:24444777

Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease

PubMed Central

Vidal-Brime, Laia; Lynn, K. Sabrina

2018-01-01

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function, and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function. Here, we summarize these key regulatory events, with emphasis on how these affect connexin multifunctionality in health and disease. PMID:29701678

Altered ulnar nerve kinematic behavior in a cadaver model of entrapment.

PubMed

Mahan, Mark A; Vaz, Kenneth M; Weingarten, David; Brown, Justin M; Shah, Sameer B

2015-06-01

Ulnar nerve entrapment at the elbow is more than a compressive lesion of the nerve. The tensile biomechanical consequences of entrapment are currently marginally understood. To evaluate the effects of tethering on the kinematics of the ulnar nerve as a model of entrapment neuropathy. The ulnar nerve was exposed in 7 fresh cadaver arms, and markers were placed at 1-cm increments along the nerve, centered on the retrocondylar region. Baseline translation (pure sliding) and strain (stretch) were measured in response to progressively increasing tension produced by varying configurations of elbow flexion and wrist extension. Then the nerves were tethered by suturing to the cubital tunnel retinaculum and again exposed to progressively increasing tension from joint positioning. In the native condition, for all joint configurations, the articular segment of the ulnar nerve exhibited greater strain than segments proximal and distal to the elbow, with a maximum strain of 28 ± 1% and translation of 11.6 ± 1.8 mm distally. Tethering the ulnar nerve suppressed translation, and the distal segment experienced strains that were more than 50% greater than its maximum strain in an untethered state. This work provides a framework for evaluating regional nerve kinematics. Suppressed translation due to tethering shifted the location of high strain from articular to more distal regions of the ulnar nerve. The authors hypothesize that deformation is thus shifted to a region of the nerve less accustomed to high strains, thereby contributing to the development of ulnar neuropathy.

Micromanaging Abdominal Aortic Aneurysms

PubMed Central

Maegdefessel, Lars; Spin, Joshua M.; Adam, Matti; Raaz, Uwe; Toh, Ryuji; Nakagami, Futoshi; Tsao, Philip S.

2013-01-01

The contribution of abdominal aortic aneurysm (AAA) disease to human morbidity and mortality has increased in the aging, industrialized world. In response, extraordinary efforts have been launched to determine the molecular and pathophysiological characteristics of the diseased aorta. This work aims to develop novel diagnostic and therapeutic strategies to limit AAA expansion and, ultimately, rupture. Contributions from multiple research groups have uncovered a complex transcriptional and post-transcriptional regulatory milieu, which is believed to be essential for maintaining aortic vascular homeostasis. Recently, novel small noncoding RNAs, called microRNAs, have been identified as important transcriptional and post-transcriptional inhibitors of gene expression. MicroRNAs are thought to “fine tune” the translational output of their target messenger RNAs (mRNAs) by promoting mRNA degradation or inhibiting translation. With the discovery that microRNAs act as powerful regulators in the context of a wide variety of diseases, it is only logical that microRNAs be thoroughly explored as potential therapeutic entities. This current review summarizes interesting findings regarding the intriguing roles and benefits of microRNA expression modulation during AAA initiation and propagation. These studies utilize disease-relevant murine models, as well as human tissue from patients undergoing surgical aortic aneurysm repair. Furthermore, we critically examine future therapeutic strategies with regard to their clinical and translational feasibility. PMID:23852016

Academic Medical Product Development: An Emerging Alliance of Technology Transfer Organizations and the CTSA

PubMed Central

Everts, Maaike; Heller, Caren; Burke, Christine; Hafer, Nathaniel; Steele, Scott

2014-01-01

Abstract To bring the benefits of science more quickly to patient care, the NIH National Center Advancing Translational Sciences (NCATS) supports programs that enhance the development, testing, and implementation of new medical products and procedures. The NCATS clinical and translational science award (CTSA) program is central to that mission; creating an academic home for clinical and translational science and supporting those involved in the discovery and development of new health‐related inventions. The technology transfer Offices (TTO) of CTSA‐funded universities can be important partners in the development process; facilitating the transfer of medical research to the commercial sector for further development and ultimately, distribution to patients. The Aggregating Intellectual Property (IP) Working Group (AWG) of the CTSA public private partnerships key function committee (PPP‐KFC) developed a survey to explore how CTSA‐funded institutions currently interface with their respective TTOs to support medical product development. The results suggest a range of relationships across institutions; approximately half have formal collaborative programs, but only a few have well‐connected programs. Models of collaborations are described and provided as examples of successful CTSA/TTO partnerships that have increased the value of health‐related inventions as measured by follow‐on funding and industry involvement; either as a consulting partner or licensee. PMID:24945893

Academic medical product development: an emerging alliance of technology transfer organizations and the CTSA.

PubMed

Rose, Lynn M; Everts, Maaike; Heller, Caren; Burke, Christine; Hafer, Nathaniel; Steele, Scott

2014-12-01

To bring the benefits of science more quickly to patient care, the NIH National Center Advancing Translational Sciences (NCATS) supports programs that enhance the development, testing, and implementation of new medical products and procedures. The NCATS clinical and translational science award (CTSA) program is central to that mission; creating an academic home for clinical and translational science and supporting those involved in the discovery and development of new health-related inventions. The technology transfer Offices (TTO) of CTSA-funded universities can be important partners in the development process; facilitating the transfer of medical research to the commercial sector for further development and ultimately, distribution to patients. The Aggregating Intellectual Property (IP) Working Group (AWG) of the CTSA public private partnerships key function committee (PPP-KFC) developed a survey to explore how CTSA-funded institutions currently interface with their respective TTOs to support medical product development. The results suggest a range of relationships across institutions; approximately half have formal collaborative programs, but only a few have well-connected programs. Models of collaborations are described and provided as examples of successful CTSA/TTO partnerships that have increased the value of health-related inventions as measured by follow-on funding and industry involvement; either as a consulting partner or licensee. © 2014 Wiley Periodicals, Inc.

Flexible scintillator autoradiography for tumor margin inspection using 18F-FDG

NASA Astrophysics Data System (ADS)

Vyas, K. N.; Grootendorst, M.; Mertzanidou, T.; Macholl, S.; Stoyanov, D.; Arridge, S. R.; Tuch, D. S.

2018-03-01

Autoradiography potentially offers high molecular sensitivity and spatial resolution for tumor margin estimation. However, conventional autoradiography requires sectioning the sample which is destructive and labor-intensive. Here we describe a novel autoradiography technique that uses a flexible ultra-thin scintillator which conforms to the sample surface. Imaging with the flexible scintillator enables direct, high-resolution and high-sensitivity imaging of beta particle emissions from targeted radiotracers. The technique has the potential to identify positive tumor margins in fresh unsectioned samples during surgery, eliminating the processing time demands of conventional autoradiography. We demonstrate the feasibility of the flexible autoradiography approach to directly image the beta emissions from radiopharmaceuticals using lab experiments and GEANT-4 simulations to determine i) the specificity for 18F compared to 99mTc-labeled tracers ii) the sensitivity to detect signal from various depths within the tissue. We found that an image resolution of 1.5 mm was achievable with a scattering background and we estimate a minimum detectable activity concentration of 0.9 kBq/ml for 18F. We show that the flexible autoradiography approach has high potential as a technique for molecular imaging of tumor margins using 18F-FDG in a tumor xenograft mouse model imaged with a radiation-shielded EMCCD camera. Due to the advantage of conforming to the specimen, the flexible scintillator showed significantly better image quality in terms of tumor signal to whole-body background noise compared to rigid and optimally thick CaF2:Eu and BC400. The sensitivity of the technique means it is suitable for clinical translation.

In vivo architectural analysis of 3.2 mm clear corneal incisions for phacoemulsification using optical coherence tomography.

PubMed

Torres, Luis F; Saez-Espinola, Fidelia; Colina, Juner M; Retchkiman, Myriam; Patel, Milan R; Agurto, Ricardo; Garcia, Gerardo; Diaz, Jose L; Huang, David; Schanzlin, David J; Chayet, Arturo S

2006-11-01

To analyze in vivo the architecture of clear corneal incisions (CCIs) for phacoemulsification using optical coherence tomography (OCT). Anterior Segment Department, Asociacion Para Evitar la Ceguera en Mexico, Hospital Dr Luis Sanchez Bulnes, Mexico. A prospective masked study analyzed 20 unsutured CCIs placed superiorly and created in a uniplanar fashion with a 3.2 mm slit-angled metal keratome. All wounds were evaluated with a retinal OCT model 1, 3, and 30 days postoperatively. Intraocular pressure (IOP) and incision leakage were checked. The architecture was described according to the angle of incidence, apposition of the epithelial and endothelial margins, and wound sealing. No leakage was detected. The angle varied from 33 to 85 degrees; angles greater than 75 degrees were done by a surgeon in training. Wound apposition at the epithelial margin was achieved in all cases. In contrast, imperfect apposition of the endothelial margin was seen in 45% of incisions on day 1 and in 15% on day 30. Incomplete sealing of the wound was seen by OCT in 25% of cases at 24 hours and persisted in 10% of all cases at 1 month. This gaping occurred on the endothelial side and never translated to the epithelial margin. No statistical correlation was found between gaping and the angle of the incision, IOP variations, or surgeon experience. Although in vivo CCIs caused minor anatomic imperfections, they were clinically stable independent of incision angle, IOP variation, and surgeon experience. Incision stability may be related to careful wound construction, epithelial viability, stromal edema, and efficient endothelial pumping.

Skin cancer margin analysis within minutes with full-field OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Dalimier, Eugénie; Ogrich, Lauren; Morales, Diego; Cusack, Carrie Ann; Abdelmalek, Mark; Boccara, Claude; Durkin, John

2017-02-01

Non-melanoma skin cancer (NMSC) is the most common cancer. Treatment consists of surgical removal of the skin cancer. Traditional excision involves the removal of the visible skin cancer with a significant margin of normal skin. On cosmetically sensitive areas, Mohs micrographic tissue is the standard of care. Mohs uses intraoperative microscopic margin assessment which minimizes the surgical defect and can help reduce the recurrence rate by a factor of 3. The current Mohs technique relies on frozen section tissue slide preparation which significantly lengthens operative time and requires on-site trained histotechnicians. Full-Field Optical Coherence Tomography (FFOCT) is a novel optical imaging technique which provides a quick and efficient method to visualize cancerous areas in minutes, without any preparation or destruction of the tissue. This study aimed to evaluate the potential of FFOCT for the analysis of skin cancer margins during Mohs surgery. Over 150 images of Mohs specimens were acquired intraoperatively with FFOCT before frozen section analysis. The imaging procedure took less than 5 minutes for each specimen. No artifacts on histological preparation were found arising from FFOCT manipulation; however frozen section artifact was readily seen on FFOCT. An atlas was established with FFOCT images and corresponding histological slides to reveal FFOCT reading criteria of normal and cancerous structures. Blind analysis showed high concordance between FFOCT and histology. FFOCT can potentially reduce recurrence rates while maintaining short surgery times, optimize clinical workflow, and decrease healthcare costs. For the patient, this translates into smaller infection risk, decreased stress, and better comfort.

Paleomagnetic evidence from land-based and ODP cores for clockwise rotation and northward translation of the Phillippine Sea plate

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

Cisowski, S.M.; Fuller, M.; Haston, R.B.

1990-06-01

On-land and deep-sea core paleomagnetic data have been collected from around the Philippine Sea plate. Data from the Palau islands suggest 70{degree} of clockwise rotation and northward translation since the mid-Oligocene. The authors interpret this rotation as a rotation of the West Philippine Sea basin as a whole. New paleomagnetic data from Guam indicate 70{degree} of clockwise rotation and northward translation since the early Oligocene. Although Eocene results have been previously quoted, the new data suggest that there is no reliable Eocene data from Guam. New data from Saipan suggest 50-60{degree} of clockwise rotation since the Late Eocene and 20{degree}more » of clockwise rotation since the mid-Miocene, along with northward translation. During ODP Leg 126, a new technique utilizing the formation microscanner logging tool was employed to obtain orientated drill cores from the Bonin forearc basin. Preliminary results indicate that 70-110{degree} of clockwise rotation has occurred there since the mid-Oligocene. Inclination studies on cores from ODP Legs 125 and 126 along with the on-land paleomagnetic data support 15{degree} of northward translation of the Philippine Sea plate since the mid-Oligocene. The consistent clockwise rotations found around the Philippine Sea plate suggest that the entire plate, including the Bonin and Mariana arcs, has rotated more than 50{degree} since the mid-Oligocene. The similarity of Oligocene results from the Bonin forearc and Guam suggest that little or no relative rotation has occurred between these two points. This implies that the shape of the Mariana arc is probably not due to rotational deformation. The northward translation and clockwise rotation of the Philippine Sea plate established oblique subduction along the proto-Philippine margin, which could account for the 600 km of subducted slab beneath the eastern Celebes Sea.« less

Translation efficiency of heterologous proteins is significantly affected by the genetic context of RBS sequences in engineered cyanobacterium Synechocystis sp. PCC 6803.

PubMed

Thiel, Kati; Mulaku, Edita; Dandapani, Hariharan; Nagy, Csaba; Aro, Eva-Mari; Kallio, Pauli

2018-03-02

Photosynthetic cyanobacteria have been studied as potential host organisms for direct solar-driven production of different carbon-based chemicals from CO 2 and water, as part of the development of sustainable future biotechnological applications. The engineering approaches, however, are still limited by the lack of comprehensive information on most optimal expression strategies and validated species-specific genetic elements which are essential for increasing the intricacy, predictability and efficiency of the systems. This study focused on the systematic evaluation of the key translational control elements, ribosome binding sites (RBS), in the cyanobacterial host Synechocystis sp. PCC 6803, with the objective of expanding the palette of tools for more rigorous engineering approaches. An expression system was established for the comparison of 13 selected RBS sequences in Synechocystis, using several alternative reporter proteins (sYFP2, codon-optimized GFPmut3 and ethylene forming enzyme) as quantitative indicators of the relative translation efficiencies. The set-up was shown to yield highly reproducible expression patterns in independent analytical series with low variation between biological replicates, thus allowing statistical comparison of the activities of the different RBSs in vivo. While the RBSs covered a relatively broad overall expression level range, the downstream gene sequence was demonstrated in a rigorous manner to have a clear impact on the resulting translational profiles. This was expected to reflect interfering sequence-specific mRNA-level interaction between the RBS and the coding region, yet correlation between potential secondary structure formation and observed translation levels could not be resolved with existing in silico prediction tools. The study expands our current understanding on the potential and limitations associated with the regulation of protein expression at translational level in engineered cyanobacteria. The acquired information can be used for selecting appropriate RBSs for optimizing over-expression constructs or multicistronic pathways in Synechocystis, while underlining the complications in predicting the activity due to gene-specific interactions which may reduce the translational efficiency for a given RBS-gene combination. Ultimately, the findings emphasize the need for additional characterized insulator sequence elements to decouple the interaction between the RBS and the coding region for future engineering approaches.

Utility of the Stanford Brief Activity Survey for physical activity assessment in postpartum Latinas: A validation study of a linguistically translated Spanish version

PubMed Central

Joseph, Rodney P.; Ainsworth, Barbara E.; Vega-López, Sonia; Keller, Colleen S.

2014-01-01

This study assessed the concurrent validity of the English and a linguistic Spanish translation of the Stanford Brief Activity Survey (SBAS) with pedometer measured physical activity (PA) among postpartum Latinas. Latinas (n = 97) completed the SBAS in either English (n = 47) or Spanish (n = 50) and wore pedometers seven days at three different assessment periods. The English version demonstrated significant trends (p < .01) for differentiating aerobic walking steps (AWS) and aerobic walking time (AWT) across SBAS intensity categories at two of the three assessment periods. The Spanish version showed marginally significant trends for differentiating AWS (p = .048) and AWT (p = .052) across SBAS intensity categories at only one assessment period. The English version of the SBAS is effective in assessing PA status among Latinas; however, the Spanish version indicates a need for research to further explore cultural and linguistic adaptations of the SBAS. PMID:25239211

Assessing Health Literacy in Deaf American Sign Language Users.

PubMed

McKee, Michael M; Paasche-Orlow, Michael K; Winters, Paul C; Fiscella, Kevin; Zazove, Philip; Sen, Ananda; Pearson, Thomas

2015-01-01

Communication and language barriers isolate Deaf American Sign Language (ASL) users from mass media, health care messages, and health care communication, which, when coupled with social marginalization, places them at a high risk for inadequate health literacy. Our objectives were to translate, adapt, and develop an accessible health literacy instrument in ASL and to assess the prevalence and correlates of inadequate health literacy among Deaf ASL users and hearing English speakers using a cross-sectional design. A total of 405 participants (166 Deaf and 239 hearing) were enrolled in the study. The Newest Vital Sign was adapted, translated, and developed into an ASL version (ASL-NVS). We found that 48% of Deaf participants had inadequate health literacy, and Deaf individuals were 6.9 times more likely than hearing participants to have inadequate health literacy. The new ASL-NVS, available on a self-administered computer platform, demonstrated good correlation with reading literacy. The prevalence of Deaf ASL users with inadequate health literacy is substantial, warranting further interventions and research.

Assessing Health Literacy in Deaf American Sign Language Users

PubMed Central

McKee, Michael M.; Paasche-Orlow, Michael; Winters, Paul C.; Fiscella, Kevin; Zazove, Philip; Sen, Ananda; Pearson, Thomas

2015-01-01

Communication and language barriers isolate Deaf American Sign Language (ASL) users from mass media, healthcare messages, and health care communication, which when coupled with social marginalization, places them at a high risk for inadequate health literacy. Our objectives were to translate, adapt, and develop an accessible health literacy instrument in ASL and to assess the prevalence and correlates of inadequate health literacy among Deaf ASL users and hearing English speakers using a cross-sectional design. A total of 405 participants (166 Deaf and 239 hearing) were enrolled in the study. The Newest Vital Sign was adapted, translated, and developed into an ASL version of the NVS (ASL-NVS). Forty-eight percent of Deaf participants had inadequate health literacy, and Deaf individuals were 6.9 times more likely than hearing participants to have inadequate health literacy. The new ASL-NVS, available on a self-administered computer platform, demonstrated good correlation with reading literacy. The prevalence of Deaf ASL users with inadequate health literacy is substantial, warranting further interventions and research. PMID:26513036

Proximity operations considerations affecting spacecraft design

NASA Technical Reports Server (NTRS)

Staas, Steven K.

1991-01-01

Proximity operations can be defined as the maneuvering of two or more spacecraft within 1 nautical mile range, with relative velocity less than 10 feet per second. The passive vehicle is nontranslating and should provide for maintenance of the desired approach attitude. It must accommodate the active (translating) vehicle induced structural loads and performance characteristics (mating hardware tolerances), and support sensor compatibility (transponder, visual targets, etc.). The active vehicle must provide adequate sensor systems (relative state information, field-of-view, redundancy), flight control hardware (thruster sizing, minimal cross-coupling, performance margins, redundancy) and software (reconfigurable, attitude/rate modes, translation and rotation fine control authority) characteristic, and adequate non-propulsive consumables such as power. Operational concerns must be considered. These include the following: (1) the desired approach trajectory and relative orientation; (2) the active vehicle thruster plume effects (forces, torques, contamination) on the passive vehicle; and (3) procedures for contingencies such as loss of communications, sensor or propulsion failures, and target vehicle loss of control.

Translation Invariant Extensions of Finite Volume Measures

NASA Astrophysics Data System (ADS)

Goldstein, S.; Kuna, T.; Lebowitz, J. L.; Speer, E. R.

2017-02-01

We investigate the following questions: Given a measure μ _Λ on configurations on a subset Λ of a lattice L, where a configuration is an element of Ω ^Λ for some fixed set Ω , does there exist a measure μ on configurations on all of L, invariant under some specified symmetry group of L, such that μ _Λ is its marginal on configurations on Λ ? When the answer is yes, what are the properties, e.g., the entropies, of such measures? Our primary focus is the case in which L=Z^d and the symmetries are the translations. For the case in which Λ is an interval in Z we give a simple necessary and sufficient condition, local translation invariance ( LTI), for extendibility. For LTI measures we construct extensions having maximal entropy, which we show are Gibbs measures; this construction extends to the case in which L is the Bethe lattice. On Z we also consider extensions supported on periodic configurations, which are analyzed using de Bruijn graphs and which include the extensions with minimal entropy. When Λ subset Z is not an interval, or when Λ subset Z^d with d>1, the LTI condition is necessary but not sufficient for extendibility. For Z^d with d>1, extendibility is in some sense undecidable.

Phanerozoic tectonic evolution of the Circum-North Pacific

USGS Publications Warehouse

Nokleberg, Warren J.; Parfenov, Leonid M.; Monger, James W.H.; Norton, Ian O.; Khanchuk, Alexander I.; Stone, David B.; Scotese, Christopher R.; Scholl, David W.; Fujita, Kazuya

2000-01-01

The Phanerozoic tectonic evolution of the Circum-North Pacific is recorded mainly in the orogenic collages of the Circum-North Pacific mountain belts that separate the North Pacific from the eastern part of the North Asian Craton and the western part of the North American Craton. These collages consist of tectonostratigraphic terranes that are composed of fragments of igneous arcs, accretionary-wedge and subduction-zone complexes, passive continental margins, and cratons; they are overlapped by continental-margin-arc and sedimentary-basin assemblages. The geologic history of the terranes and overlap assemblages is highly complex because of postaccretionary dismemberment and translation during strike-slip faulting that occurred subparallel to continental margins.We analyze the complex tectonics of this region by the following steps. (1) We assign tectonic environments for the orogenic collages from regional compilation and synthesis of stratigraphic and faunal data. The types of tectonic environments include cratonal, passive continental margin, metamorphosed continental margin, continental-margin arc, island arc, oceanic crust, seamount, ophiolite, accretionary wedge, subduction zone, turbidite basin, and metamorphic. (2) We make correlations between terranes. (3) We group coeval terranes into a single tectonic origin, for example, a single island arc or subduction zone. (4) We group igneous-arc and subduction- zone terranes, which are interpreted as being tectonically linked, into coeval, curvilinear arc/subduction-zone complexes. (5) We interpret the original positions of terranes, using geologic, faunal, and paleomagnetic data. (6) We construct the paths of tectonic migration. Six processes overlapping in time were responsible for most of the complexities of the collage of terranes and overlap assemblages around the Circum-North Pacific, as follows. (1) During the Late Proterozoic, Late Devonian, and Early Carboniferous, major periods of rifting occurred along the ancestral margins of present-day Northeast Asia and northwestern North America. The rifting resulted in the fragmentation of each continent and the formation of cratonal and passive continental-margin terranes that eventually migrated and accreted to other sites along the evolving margins of the original or adjacent continents. (2) From about the Late Triassic through the mid-Cretaceous, a succession of island arcs and tectonically paired subduction zones formed near the continental margins. (3) From about mainly the mid-Cretaceous through the present, a succession of igneous arcs and tectonically paired subduction zones formed along the continental margins. (4) From about the Jurassic to the present, oblique convergence and rotations caused orogenparallel sinistral and then dextral displacements within the upper-plate margins of cratons that have become Northeast Asia and North America. The oblique convergences and rotations resulted in the fragmentation, displacement, and duplication of formerly more nearly continuous arcs, subduction zones, and passive continental margins. These fragments were subsequently accreted along the expanding continental margins. (5) From the Early Jurassic through Tertiary, movement of the upper continental plates toward subduction zones resulted in strong plate coupling and accretion of the former island arcs and subduction zones to the continental margins. Accretions were accompanied and followed by crustal thickening, anatexis, metamorphism, and uplift. The accretions resulted in substantial growth of the North Asian and North American Continents. (6) During the middle and late Cenozoic, oblique to orthogonal convergence of the Pacifi c plate with present-day Alaska and Northeast Asia resulted in formation of the modern-day ring of volcanoes around the Circum-North Pacific. Oblique convergence between the Pacific plate and Alaska also resulted in major dextral-slip faulting in interior and southern Alaska and along the western p

Reliability, validity, and responsiveness of the Persian version of Shoulder Activity Scale in a group of patients with shoulder disorders.

PubMed

Negahban, Hossein; Mohtasebi, Elham; Goharpey, Shahin

2015-01-01

The aim of this methodological study was to cross-culturally translate the Shoulder Activity Scale (SAS) into the Persian and determine its clinimetric properties including reliability, validity, and responsiveness in patients with shoulder disorders. Persian version of the SAS was obtained after standard forward-backward translation. Three questionnaires were completed by the respondents: SAS, shoulder pain and disability index (SPADI), and Short-Form 36 Health Survey (SF-36). The patients completed the SAS, 1 week after the first visit to evaluate the test-retest reliability. Construct validity was evaluated by examining the associations between the scores on the SAS and the scores obtained from the SPADI, SF-36, and age of the patients. To assess responsiveness, data were collected in the first visit and then again after 4 weeks physiotherapy intervention. Test-retest reliability and internal consistency were assessed using Intra-class Correlation Coefficient (ICC) and Cronbach's alpha, respectively. To evaluate construct validity, Spearman's rank correlation was used. The ability of the SAS to detect changes was evaluated by the receiver-operating characteristics method. No problem or language difficulties were reported during translation process. Test-retest reliability of the SAS was excellent with an ICC of 0.98. Also, the marginal Cronbach's alpha level of 0.64 was obtained. The correlation between the SAS and the SPADI was low, proving divergent validity, whereas the correlations between the SAS and the SF-36/age were moderate proving convergent validity. A marginally acceptable responsiveness was achieved for the Persian SAS. The study provides some evidences to support the test-retest reliability, internal consistency, construct validity, and responsiveness of the Persian version of the SAS in patients with shoulder disorders. Therefore, it seems that this instrument is a useful measure of shoulder activity level in research setting and clinical practice. The shoulder activity scale (SAS) is a reliable, valid, and responsive measure of shoulder activity level in Persian-speaking patients with different shoulder disorders. The results on clinimetric properties of the Persian SAS are comparable with its original, English version. Persian version of the SAS can be used in "clinical" and "research" settings of patients with shoulder disorders.

Adaptation of an evidence-based intervention to promote colorectal cancer screening: a quasi-experimental study

PubMed Central

2014-01-01

Background To accelerate the translation of research findings into practice for underserved populations, we investigated the adaptation of an evidence-based intervention (EBI), designed to increase colorectal cancer (CRC) screening in one limited English-proficient (LEP) population (Chinese), for another LEP group (Vietnamese) with overlapping cultural and health beliefs. Methods Guided by Diffusion of Innovations Theory, we adapted the EBI to achieve greater reach. Core elements of the adapted intervention included: small media (a DVD and pamphlet) translated into Vietnamese from Chinese; medical assistants distributing the small media instead of a health educator; and presentations on CRC screening to the medical assistants. A quasi-experimental study examined CRC screening adherence among eligible Vietnamese patients at the intervention and control clinics, before and after the 24-month intervention. The proportion of the adherence was assessed using generalized linear mixed models that account for clustering under primary care providers and also within-patient correlation between baseline and follow up. Results Our study included two cross-sectional samples: 1,016 at baseline (604 in the intervention clinic and 412 in the control clinic) and 1,260 post-intervention (746 in the intervention and 514 in the control clinic), including appreciable overlaps between the two time points. Pre-post change in CRC screening over time, expressed as an odds ratio (OR) of CRC screening adherence by time, showed a marginally-significant greater increase in CRC screening adherence at the intervention clinic compared to the control clinic (the ratio of the two ORs = 1.42; 95% CI 0.95, 2.15). In the sample of patients who were non-adherent to CRC screening at baseline, compared to the control clinic, the intervention clinic had marginally-significant greater increase in FOBT (adjusted OR = 1.77; 95% CI 0.98, 3.18) and a statistically-significantly greater increase in CRC screening adherence (adjusted OR = 1.70; 95% CI 1.05, 2.75). Conclusions Theoretically guided adaptations of EBIs may accelerate the translation of research into practice. Adaptation has the potential to mitigate health disparities for hard-to-reach populations in a timely manner. PMID:24989083

Differential preservation in the geologic record of intraoceanic arc sedimentary and tectonic processes

USGS Publications Warehouse

Draut, Amy; Clift, Peter D.

2013-01-01

Records of ancient intraoceanic arc activity, now preserved in continental suture zones, are commonly used to reconstruct paleogeography and plate motion, and to understand how continental crust is formed, recycled, and maintained through time. However, interpreting tectonic and sedimentary records from ancient terranes after arc–continent collision is complicated by preferential preservation of evidence for some arc processes and loss of evidence for others. In this synthesis we examine what is lost, and what is preserved, in the translation from modern processes to the ancient record of intraoceanic arcs. Composition of accreted arc terranes differs as a function of arc–continent collision geometry. ‘Forward-facing’ collision can accrete an oceanic arc on to either a passive or an active continental margin, with the arc facing the continent and colliding trench- and forearc-side first. In a ‘backward-facing’ collision, involving two subduction zones with similar polarity, the arc collides backarc-first with an active continental margin. The preservation of evidence for contemporary sedimentary and tectonic arc processes in the geologic record depends greatly on how well the various parts of the arc survive collision and orogeny in each case. Preservation of arc terranes likely is biased towards those that were in a state of tectonic accretion for tens of millions of years before collision, rather than tectonic erosion. The prevalence of tectonic erosion in modern intraoceanic arcs implies that valuable records of arc processes are commonly destroyed even before the arc collides with a continent. Arc systems are most likely to undergo tectonic accretion shortly before forward-facing collision with a continent, and thus most forearc and accretionary-prism material in ancient arc terranes likely is temporally biased toward the final stages of arc activity, when sediment flux to the trench was greatest and tectonic accretion prevailed. Collision geometry and tectonic erosion vs. accretion are important controls on the ultimate survival of material from the trench, forearc, arc massif, intra-arc basins, and backarc basins, and thus on how well an ancient arc terrane preserves evidence for tectonic processes such as subduction of aseismic ridges and seamounts, oblique plate convergence, and arc rifting. Forward-facing collision involves substantial recycling, melting, and fractionation of continent-derived material during and after collision, and so produces melts rich in silica and incompatible trace elements. As a result, forward-facing collision can drive the composition of accreted arc crust toward that of average continental crust.

Translational reciprocity: bridging the gap between preclinical studies and clinical treatment of stress effects on the adolescent brain.

PubMed

Neigh, G N; Ritschel, L A; Kilpela, L S; Harrell, C S; Bourke, C H

2013-09-26

The genetic, biological, and environmental backgrounds of an organism fundamentally influence the balance between risk and resilience to stress. Sex, age, and environment transact with responses to trauma in ways that can mitigate or exacerbate the likelihood that post-traumatic stress disorder will develop. Translational approaches to modeling affective disorders in animals will ultimately provide novel treatments and a better understanding of the neurobiological underpinnings behind these debilitating disorders. The extant literature on trauma/stress has focused predominately on limbic and cortical structures that innervate the hypothalamic-pituitary-adrenal axis and influence glucocorticoid-mediated negative feedback. It is through these neuroendocrine pathways that a self-perpetuating fear memory can propagate the long-term effects of early life trauma. Recent work incorporating translational approaches has provided novel pathways that can be influenced by early life stress, such as the glucocorticoid receptor chaperones, including FKBP51. Animal models of stress have differing effects on behavior and endocrine pathways; however, complete models replicating clinical characteristics of risk and resilience have not been rigorously studied. This review discusses a four-factor model that considers the importance of studying both risk and resilience in understanding the developmental response to trauma/stress. Consideration of the multifactorial nature of clinical populations in the design of preclinical models and the application of preclinical findings to clinical treatment approaches comprise the core of translational reciprocity, which is discussed in the context of the four-factor model. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Influence of pre-salt topographic features on supra-salt deformation in Mediterranean basins: Geology vs. physical models

NASA Astrophysics Data System (ADS)

Ferrer, Oriol; Vidal-Royo, Oskar; Gratacós, Oscar; Roca, Eduard; Muñoz, Josep Anton; Esestime, Paolo; Rodriguez, Karyna; Yazmin Piragauta, Mary; Feliu, Nil

2017-04-01

The presence of a thick Messinian evaporite unit is a well known feature of the Mediterranean basins. This salt unit is composed of three sub-units (Lower, Mobile and Upper Units) in the Northwest Mediterranean. In contrast, in the Eastern Mediterranean it is characterized by a multilayered evaporite sequence. In both regions the salt acted as a detachment favoring the downslope gravitational failure of the overlying sediments in a thin-skinned deformation regime (e.g. Liguro-Provençal or Levant basins). As a result, these salt-bearing passive margins exhibit the classical three-domain structural zonation characterized by upslope extension, intermediate translation and downslope contraction. Nevertheless, the presence of pre-salt reliefs (e.g. irregularly eroded palaeotopography or volcanic edifices) is rather common in the translational domain of the Northwestern Mediterranean (e.g. Liguro-Provençal and West Corsica margins). In this scenario, pre-salt reliefs act as flow barriers and hinder salt drainage. When their summit lies close or above the top salt, these structures may partially or fully block salt flow. They also disrupt locally the structural zonation of the passive margin and constrain cover deformation. In contrast, in the Eastern Mediterranean the Eratosthenes seamount is characterized by a large scale submerged massif (ca. 120 km in size) that significantly influenced the structural evolution of the surrounding areas. This inherited relief acted as a buttress and deflected the Messinian salt flow constraining supra-salt deformation (e.g. Levant Basin and Nile margin). In addition, the geometry of the Eratosthenes seamount also restrained the structural style of the allochthonous salt that was expulsed during the development of the Cyprus subduction zone to the north. Using an experimental approach (sandbox models) and new analysis techniques, we investigate salt and supra-salt deformation in response to two different types of pre-salt relief: 1) local seamounts during gravitational gliding (Western Mediterranean) and, 2) large regional reliefs during the emplacement of a thrust system (Eastern Mediterranean). The experimental results of the Western Mediterranean show that the geometry, continuity and orientation of these reliefs with respect to the margin slope are key factors during gravitational failure and influence supra-salt deformation. Experimental results in the Eastern Mediterranean indicate that different responses are obtained along-strike as a consequence of shortening when modeling the Eratosthenes seamount. These differences were basically controlled by the location of the seamount, that was a topographic high during the deposition of the Messinian evaporites. The presence of seamounts in the contractional domain, instead, initially enhanced salt inflation by buttressing and the subsequent development of salt sheets with the formation of an escarpment at the edge of the salt. The experimental results also provide geometrical constraints to bear in mind during interpretation of these structures and associated hydrocarbon plays, which are commonly poorly imaged in seismic data.

Structure-based design of Trifarotene (CD5789), a potent and selective RARγ agonist for the treatment of acne.

PubMed

Thoreau, Etienne; Arlabosse, Jean-Marie; Bouix-Peter, Claire; Chambon, Sandrine; Chantalat, Laurent; Daver, Sébastien; Dumais, Laurence; Duvert, Gwenaëlle; Feret, Angélique; Ouvry, Gilles; Pascau, Jonathan; Raffin, Catherine; Rodeville, Nicolas; Soulet, Catherine; Tabet, Samuel; Talano, Sandrine; Portal, Thibaud

2018-06-01

Retinoids have a dominant role in topical acne therapy and to date, only RARβ and RARγ dual agonists have reached the market. Given the tissue distribution of RAR isoforms, it was hypothesized that developing RARγ -selective agonists could yield a new generation of topical acne treatments that would increase safety margins while maintaining the robust efficacy of previous drugs. Structural knowledge derived from the X-ray structure of known γ-selective CD437, suggested the design of a novel triaryl series of agonists which was optimized and ultimately led to the discovery of Trifarotene/CD5789. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Body Mass Index on Magnitude of Setup Errors in Patients Treated With Adjuvant Radiotherapy for Endometrial Cancer With Daily Image Guidance

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

Lin, Lilie L., E-mail: lin@uphs.upenn.edu; Hertan, Lauren; Rengan, Ramesh

2012-06-01

Purpose: To determine the impact of body mass index (BMI) on daily setup variations and frequency of imaging necessary for patients with endometrial cancer treated with adjuvant intensity-modulated radiotherapy (IMRT) with daily image guidance. Methods and Materials: The daily shifts from a total of 782 orthogonal kilovoltage images from 30 patients who received pelvic IMRT between July 2008 and August 2010 were analyzed. The BMI, mean daily shifts, and random and systematic errors in each translational and rotational direction were calculated for each patient. Margin recipes were generated based on BMI. Linear regression and spearman rank correlation analysis were performed.more » To simulate a less-than-daily IGRT protocol, the average shift of the first five fractions was applied to subsequent setups without IGRT for assessing the impact on setup error and margin requirements. Results: Median BMI was 32.9 (range, 23-62). Of the 30 patients, 16.7% (n = 5) were normal weight (BMI <25); 23.3% (n = 7) were overweight (BMI {>=}25 to <30); 26.7% (n = 8) were mildly obese (BMI {>=}30 to <35); and 33.3% (n = 10) were moderately to severely obese (BMI {>=} 35). On linear regression, mean absolute vertical, longitudinal, and lateral shifts positively correlated with BMI (p = 0.0127, p = 0.0037, and p < 0.0001, respectively). Systematic errors in the longitudinal and vertical direction were found to be positively correlated with BMI category (p < 0.0001 for both). IGRT for the first five fractions, followed by correction of the mean error for all subsequent fractions, led to a substantial reduction in setup error and resultant margin requirement overall compared with no IGRT. Conclusions: Daily shifts, systematic errors, and margin requirements were greatest in obese patients. For women who are normal or overweight, a planning target margin margin of 7 to 10 mm may be sufficient without IGRT, but for patients who are moderately or severely obese, this is insufficient.« less

"We don't exist": a qualitative study of marginalization experienced by HIV-positive lesbian, bisexual, queer and transgender women in Toronto, Canada.

PubMed

Logie, Carmen H; James, Llana; Tharao, Wangari; Loutfy, Mona R

2012-09-07

Lesbian, bisexual, queer and transgender (LBQT) women living with HIV have been described as invisible and understudied. Yet, social and structural contexts of violence and discrimination exacerbate the risk of HIV infection among LBQT women. The study objective was to explore challenges in daily life and experiences of accessing HIV services among HIV-positive LBQT women in Toronto, Canada. We used a community-based qualitative approach guided by an intersectional theoretical framework. We conducted two focus groups; one focus group was conducted with HIV-positive lesbian, bisexual and queer women (n = 7) and the second with HIV-positive transgender women (n = 16). Participants were recruited using purposive sampling. Focus groups were digitally recorded and transcribed verbatim. Thematic analysis was used for analyzing data to enhance understanding of factors that influence the wellbeing of HIV-positive LBQT women. Participant narratives revealed a trajectory of marginalization. Structural factors such as social exclusion and violence elevated the risk for HIV infection; this risk was exacerbated by inadequate HIV prevention information. Participants described multiple barriers to HIV care and support, including pervasive HIV-related stigma, heteronormative assumptions in HIV-positive women's services and discriminatory and incompetent treatment by health professionals. Underrepresentation of LBQT women in HIV research further contributed to marginalization and exclusion. Participants expressed a willingness to participate in HIV research that would be translated into action. Structural factors elevate HIV risk among LBQT women, limit access to HIV prevention and present barriers to HIV care and support. This study's conceptualization of a trajectory of marginalization enriches the discussion of structural factors implicated in the wellbeing of LBQT women and highlights the necessity of addressing LBQT women's needs in HIV prevention, care and research. Interventions that address intersecting forms of marginalization (e.g. sexual stigma, transphobia, HIV-related stigma) in community and social norms, HIV programming and research are required to promote health equity among LBQT women.

“We don't exist”: a qualitative study of marginalization experienced by HIV-positive lesbian, bisexual, queer and transgender women in Toronto, Canada

PubMed Central

Logie, Carmen H; James, LLana; Tharao, Wangari; Loutfy, Mona R

2012-01-01

Background Lesbian, bisexual, queer and transgender (LBQT) women living with HIV have been described as invisible and understudied. Yet, social and structural contexts of violence and discrimination exacerbate the risk of HIV infection among LBQT women. The study objective was to explore challenges in daily life and experiences of accessing HIV services among HIV-positive LBQT women in Toronto, Canada. Methods We used a community-based qualitative approach guided by an intersectional theoretical framework. We conducted two focus groups; one focus group was conducted with HIV-positive lesbian, bisexual and queer women (n=7) and the second with HIV-positive transgender women (n=16). Participants were recruited using purposive sampling. Focus groups were digitally recorded and transcribed verbatim. Thematic analysis was used for analyzing data to enhance understanding of factors that influence the wellbeing of HIV-positive LBQT women. Results Participant narratives revealed a trajectory of marginalization. Structural factors such as social exclusion and violence elevated the risk for HIV infection; this risk was exacerbated by inadequate HIV prevention information. Participants described multiple barriers to HIV care and support, including pervasive HIV-related stigma, heteronormative assumptions in HIV-positive women's services and discriminatory and incompetent treatment by health professionals. Underrepresentation of LBQT women in HIV research further contributed to marginalization and exclusion. Participants expressed a willingness to participate in HIV research that would be translated into action. Conclusions Structural factors elevate HIV risk among LBQT women, limit access to HIV prevention and present barriers to HIV care and support. This study's conceptualization of a trajectory of marginalization enriches the discussion of structural factors implicated in the wellbeing of LBQT women and highlights the necessity of addressing LBQT women's needs in HIV prevention, care and research. Interventions that address intersecting forms of marginalization (e.g. sexual stigma, transphobia, HIV-related stigma) in community and social norms, HIV programming and research are required to promote health equity among LBQT women. PMID:22989529

Alzheimer's disease, β-amyloid, glutamate, NMDA receptors and memantine – searching for the connections

PubMed Central

Danysz, Wojciech; Parsons, Chris G

2012-01-01

β-amyloid (Aβ) is widely accepted to be one of the major pathomechanisms underlying Alzheimer's disease (AD), although there is presently lively debate regarding the relative roles of particular species/forms of this peptide. Most recent evidence indicates that soluble oligomers rather than plaques are the major cause of synaptic dysfunction and ultimately neurodegeneration. Soluble oligomeric Aβ has been shown to interact with several proteins, for example glutamatergic receptors of the NMDA type and proteins responsible for maintaining glutamate homeostasis such as uptake and release. As NMDA receptors are critically involved in neuronal plasticity including learning and memory, we felt that it would be valuable to provide an up to date review of the evidence connecting Aβ to these receptors and related neuronal plasticity. Strong support for the clinical relevance of such interactions is provided by the NMDA receptor antagonist memantine. This substance is the only NMDA receptor antagonist used clinically in the treatment of AD and therefore offers an excellent tool to facilitate translational extrapolations from in vitro studies through in vivo animal experiments to its ultimate clinical utility. PMID:22646481

Sinking Jelly-Carbon Unveils Potential Environmental Variability along a Continental Margin

PubMed Central

Lebrato, Mario; Molinero, Juan-Carlos; Cartes, Joan E.; Lloris, Domingo; Mélin, Frédéric; Beni-Casadella, Laia

2013-01-01

Particulate matter export fuels benthic ecosystems in continental margins and the deep sea, removing carbon from the upper ocean. Gelatinous zooplankton biomass provides a fast carbon vector that has been poorly studied. Observational data of a large-scale benthic trawling survey from 1994 to 2005 provided a unique opportunity to quantify jelly-carbon along an entire continental margin in the Mediterranean Sea and to assess potential links with biological and physical variables. Biomass depositions were sampled in shelves, slopes and canyons with peaks above 1000 carcasses per trawl, translating to standing stock values between 0.3 and 1.4 mg C m2 after trawling and integrating between 30,000 and 175,000 m2 of seabed. The benthopelagic jelly-carbon spatial distribution from the shelf to the canyons may be explained by atmospheric forcing related with NAO events and dense shelf water cascading, which are both known from the open Mediterranean. Over the decadal scale, we show that the jelly-carbon depositions temporal variability paralleled hydroclimate modifications, and that the enhanced jelly-carbon deposits are connected to a temperature-driven system where chlorophyll plays a minor role. Our results highlight the importance of gelatinous groups as indicators of large-scale ecosystem change, where jelly-carbon depositions play an important role in carbon and energy transport to benthic systems. PMID:24367499

Continental Margins and the Law of the Sea - an `Arranged Marriage' with Huge Research Potential

NASA Astrophysics Data System (ADS)

Parson, L.

2005-12-01

The United Nations Convention on the Law of the Sea (UNCLOS) requires coastal states intending to secure sovereignty over continental shelf territory extending beyond 200 nautical miles to submit geological/geophysical data, along with their analysis and synthesis of the relevant continental margin in support of their claim. These submissions are scrutinised and assessed by a UN Commission of experts who decide if the claim is justified, and thereby ultimately allowing the exploitation of non-living resources into this extended maritime space. The amount of data required to support the case will vary from margin to margin, depending on the local geological evolution, but typically will involve the running of new, dedicated marine surveys, mostly bathymetric and seismic. Key geological/geophysical issues revolve around proof of `naturalness' of the prolongation of land mass (cue - wide-angle seismics, deep drilling and sampling programmes) and shelf and slope morphology and sediment section thickness (cue - swath bathymetry and multichannel seismics programmes). These surveys, probably primarily funded by government agencies anxious not to lose out on the `land grab', will generate datasets which will inevitably boost not only the research effort leading to increased understanding of margin evolution in academic terms, but also contribute to wider applied aspects of the work such as those leading to refinement of deepwater hydrocarbon resource potential. It is conservatively estimated that in the region of fifty coastal states world-wide have a significant potential for claiming continental shelf beyond 200 nautical miles, and that the total area available as extended shelf could easily exceed 7 million square kilometres. However, while for the vast majority of these states a UNCLOS deadline of 2009 exists for submitting a claim - to date only four have done so (Russia, Brazil, Australia and Ireland). It is therefore predictable, if not inevitable, that within the next four years an unprecedented phase of surveying and analysis on margins will take place in order to prepare for the deadline. The international scientific community as a whole must recognise the potential for research in this work and ensure the data is made available as soon as practically possible for the scientific community. In conclusion, by way of a reality check, this presentation highlights the likely areas of most intense UNCLOS-driven research activity up to 2009, the type of data acquisition anticipated and their likely location, and speculates on the areas of understanding of margin evolution which will be most advanced by this process.

Perspectives of an Interdisciplinaryg Research Team to Engage Practice: Lessons from a Knowledge Exchange Trainee Experience

PubMed Central

Urquhart, Robin L.; Johnston, Grace M.; McVorran, Shauna M.; Burge, Fred I.

2010-01-01

End-of-life (EOL) care is an area of health services that will ultimately affect us all. To share the knowledge emerging from EOL research and to address inequities in the quality of EOL care in Nova Scotia, a knowledge exchange (KE) trainee was hired to translate research and surveillance into a Surveillance Report. The purpose of this paper is to reflect upon this initiative and share the research team's perspectives on their KE experiences. We describe four key competencies of the KE trainee selected, and discuss lessons learned from this KE trainee experience, to expand our understanding of KE. PMID:21532769

Cancer heterogeneity: origins and implications for genetic association studies

PubMed Central

Urbach, Davnah; Lupien, Mathieu; Karagas, Margaret R.; Moore, Jason H.

2012-01-01

Genetic association studies have become standard approaches to characterize the genetic and epigenetic variability associated with cancer development, including predispositions and mutations. However, the bewildering genetic and phenotypic heterogeneity inherent in cancer both magnifies the conceptual and methodological problems associated with these approaches and renders the translation of available genetic information into a knowledge that is both biologically sound and clinically relevant difficult. Here, we elaborate on the underlying causes of this complexity, illustrate why it represents a challenge for genetic association studies, and briefly discuss how it can be reconciled with the ultimate goal of identifying targetable disease pathways and successfully treating individual patients. PMID:22858414

Editorial Commentary: "Virtual Reality" Simulation in Orthopaedic Surgery: Realistically Helpful, or Virtually Useless?

PubMed

Camp, Christopher L

2018-05-01

Although we have come a long way, the rapidly expanding field of virtual reality simulation for arthroscopic surgical skills acquisition is supported by only a limited amount of evidence. That said, the good news is that the evidence suggests that simulator experience translates into improved performance in the operating room. If proving this relation is our ultimate goal, more work is certainly needed. In this commentary, a "Task List" is proposed for surgeons and educators interested in using simulators and better defining their role in resident education. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Cancer cachexia: mediators, signaling, and metabolic pathways.

PubMed

Fearon, Kenneth C H; Glass, David J; Guttridge, Denis C

2012-08-08

Cancer cachexia is characterized by a significant reduction in body weight resulting predominantly from loss of adipose tissue and skeletal muscle. Cachexia causes reduced cancer treatment tolerance and reduced quality and length of life, and remains an unmet medical need. Therapeutic progress has been impeded, in part, by the marked heterogeneity of mediators, signaling, and metabolic pathways both within and between model systems and the clinical syndrome. Recent progress in understanding conserved, molecular mechanisms of skeletal muscle atrophy/hypertrophy has provided a downstream platform for circumventing the variations and redundancy in upstream mediators and may ultimately translate into new targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

Mechanisms of Tooth Eruption and Orthodontic Tooth Movement

PubMed Central

Wise, G.E.; King, G.J.

2008-01-01

Teeth move through alveolar bone, whether through the normal process of tooth eruption or by strains generated by orthodontic appliances. Both eruption and orthodontics accomplish this feat through similar fundamental biological processes, osteoclastogenesis and osteogenesis, but there are differences that make their mechanisms unique. A better appreciation of the molecular and cellular events that regulate osteoclastogenesis and osteogenesis in eruption and orthodontics is not only central to our understanding of how these processes occur, but also is needed for ultimate development of the means to control them. Possible future studies in these areas are also discussed, with particular emphasis on translation of fundamental knowledge to improve dental treatments. PMID:18434571

Probabilistic objective functions for margin-less IMRT planning

NASA Astrophysics Data System (ADS)

Bohoslavsky, Román; Witte, Marnix G.; Janssen, Tomas M.; van Herk, Marcel

2013-06-01

We present a method to implement probabilistic treatment planning of intensity-modulated radiation therapy using custom software plugins in a commercial treatment planning system. Our method avoids the definition of safety-margins by directly including the effect of geometrical uncertainties during optimization when objective functions are evaluated. Because the shape of the resulting dose distribution implicitly defines the robustness of the plan, the optimizer has much more flexibility than with a margin-based approach. We expect that this added flexibility helps to automatically strike a better balance between target coverage and dose reduction for surrounding healthy tissue, especially for cases where the planning target volume overlaps organs at risk. Prostate cancer treatment planning was chosen to develop our method, including a novel technique to include rotational uncertainties. Based on population statistics, translations and rotations are simulated independently following a marker-based IGRT correction strategy. The effects of random and systematic errors are incorporated by first blurring and then shifting the dose distribution with respect to the clinical target volume. For simplicity and efficiency, dose-shift invariance and a rigid-body approximation are assumed. Three prostate cases were replanned using our probabilistic objective functions. To compare clinical and probabilistic plans, an evaluation tool was used that explicitly incorporates geometric uncertainties using Monte-Carlo methods. The new plans achieved similar or better dose distributions than the original clinical plans in terms of expected target coverage and rectum wall sparing. Plan optimization times were only about a factor of two higher than in the original clinical system. In conclusion, we have developed a practical planning tool that enables margin-less probability-based treatment planning with acceptable planning times, achieving the first system that is feasible for clinical implementation.

Improving ethical and participatory practice for marginalized populations in biomedical HIV prevention trials: lessons from Thailand.

PubMed

Allman, Dan; Ditmore, Melissa Hope; Kaplan, Karyn

2014-01-01

This paper presents findings from a qualitative investigation of ethical and participatory issues related to the conduct of biomedical HIV prevention trials among marginalized populations in Thailand. This research was deemed important to conduct, as several large-scale biomedical HIV prevention trials among marginalized populations had closed prematurely in other countries, and a better understanding of how to prevent similar trial closures from occurring in the future was desired. In-depth key informant interviews were held in Bangkok and Chiang Mai, Thailand. Interviews were audio recorded, transcribed, translated and thematically analyzed. The Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials (GPP) guided this work. Fourteen interviews were conducted: 10 with policymakers, academic and community-based researchers and trial staff and four with representatives of non-governmental organizations (NGOs). Suggested ways to improve ethical and participatory practice centered on standards of HIV prevention, informed consent, communication and human rights. In particular, the need to overcome language and literacy differences was identified. Key informants felt communication was the basis of ethical understanding and trust within biomedical HIV prevention trial contexts, and thus fundamental to trial participants' ability to exercise free will. Biomedical HIV prevention trials present opportunities for inclusive and productive ethical and participatory practice. Key informants suggested that efforts to improve practice could result in better relationships between research stakeholders and research investigative teams and by extension, better, more ethical participatory trials. This research took place in Thailand and its findings apply primarily to Thailand. However, given the universality of many ethical considerations, the results of this study can inform the improvement of ethical and participatory practice in other parts of the world where biomedical HIV prevention trials occur, and where clinical trials in marginalized populations continue.

A Logic Model for Community Engagement within the CTSA Consortium: Can We Measure What We Model?

PubMed Central

Eder, Milton Mickey; Carter-Edwards, Lori; Hurd, Thelma C.; Rumala, Bernice B.; Wallerstein, Nina

2013-01-01

The Clinical Translation Science Award (CTSA) initiative calls upon academic health centers to engage communities around a clinical research relationship measured ultimately in terms of public health. Among a few initiatives involving university accountability for advancing public interests, a small CTSA workgroup devised a community engagement (CE) logic model that organizes common activities within a university-community infrastructure to facilitate community engagement in research. While the model focuses on the range of institutional CE inputs, it purposefully does not include an approach for assessing how community engagement influences research implementation and outcomes. Rather, with communities and individuals beginning to transition into new research roles, this article emphasizes studying community engagement through specific relationship types and assessing how expanded research teams contribute to the full spectrum of translational science. The authors propose a typology consisting of three relationship types—engagement, collaboration and shared leadership—to provide a foundation for investigating community–academic contributions to the new CTSA research paradigm. The typology shifts attention from specific community–academic activities and, instead, encourages analyses focused on measuring the strength of relationships through variables like synergy and trust. The collaborative study of CE relationships will inform an understanding of CTSA infrastructure development in support of translational research and its goal, which is expressed in the logic model: better science, better answers, better population health. PMID:23752038

Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.

2014-01-01

Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury. PMID:25414098

Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: emerging translational approaches that bridge biology and behavior.

PubMed

Feldstein Ewing, Sarah W; Chung, Tammy

2013-06-01

Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real-time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examine brain-based mechanisms of change, whereas others examine brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors. 2013 APA, all rights reserved

Designing for Broad Understanding of Science.

PubMed

Hristov, Nickolay; Strohecker, Carol; Allen, Louise; Merson, Martha

2018-06-04

With the acceleration and increasing complexity of macro-scale problems such as climate change, the need for scientists to ensure that their work is understood has become urgent. As citizens and recipients of public funds for research, scientists have an obligation to communicate their findings in ways many people can understand. However, developing translations that are broadly accessible without being "dumbed down" can be challenging. Fortunately, tenets of visual literacy, combined with narrative methods, can help to convey scientific knowledge with fidelity, while sustaining viewers' interest. Here we outline strategies for such translating, with an emphasis on visual approaches. Among the examples is an innovative, NSF-funded professional development initiative in which National Park rangers use scientists' imagery to create compelling explanations for the visiting public. Thoughtful visualizations based on interpretive images, motion pictures, 3D animations and augmented, immersive experiences complement the impact of the natural resource and enhance the role of the park ranger. The visualizations become scaffolds for participatory exchanges in which the ranger transcends the traditional roles of information-holder and presenter, to facilitate provocative conversations that provide members of the public with enjoyable experiences and well-founded bases for reflection and ultimately understanding. The process of generating the supporting visualizations benefits from partnerships with design professionals, who develop opportunities for engaging the public by translating important scientific findings and messages in compelling and memorable ways.

Nanomedicine applied to translational oncology: A future perspective on cancer treatment.

PubMed

Bregoli, Lisa; Movia, Dania; Gavigan-Imedio, James D; Lysaght, Joanne; Reynolds, John; Prina-Mello, Adriele

2016-01-01

The high global incidence of cancer is associated with high rates of mortality and morbidity worldwide. By taking advantage of the properties of matter at the nanoscale, nanomedicine promises to develop innovative drugs with greater efficacy and less side effects than standard therapies. Here, we discuss both clinically available anti-cancer nanomedicines and those en route to future clinical application. The properties, therapeutic value, advantages and limitations of these nanomedicine products are highlighted, with a focus on their increased performance versus conventional molecular anticancer therapies. The main regulatory challenges toward the translation of innovative, clinically effective nanotherapeutics are discussed, with a view to improving current approaches to the clinical management of cancer. Ultimately, it becomes clear that the critical steps for clinical translation of nanotherapeutics require further interdisciplinary and international effort, where the whole stakeholder community is involved from bench to bedside. From the Clinical Editor: Cancer is a leading cause of mortality worldwide and finding a cure remains the holy-grail for many researchers and clinicians. The advance in nanotechnology has enabled novel strategies to develop in terms of cancer diagnosis and therapy. In this concise review article, the authors described current capabilities in this field and outlined comparisons with existing drugs. The difficulties in bringing new drugs to the clinics were also discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuroimaging mechanisms of change in psychotherapy for addictive behaviors: Emerging translational approaches that bridge biology and behavior

PubMed Central

Feldstein Ewing, Sarah W.; Chung, Tammy

2013-01-01

Research on mechanisms of behavior change provides an innovative method to improve treatment for addictive behaviors. An important extension of mechanisms of change research involves the use of translational approaches, which examine how basic biological (i.e., brain-based mechanisms) and behavioral factors interact in initiating and sustaining positive behavior change as a result of psychotherapy. Articles in this special issue include integrative conceptual reviews and innovative empirical research on brain-based mechanisms that may underlie risk for addictive behaviors and response to psychotherapy from adolescence through adulthood. Review articles discuss hypothesized mechanisms of change for cognitive and behavioral therapies, mindfulness-based interventions, and neuroeconomic approaches. Empirical articles cover a range of addictive behaviors, including use of alcohol, cigarettes, marijuana, cocaine, and pathological gambling and represent a variety of imaging approaches including fMRI, magneto-encephalography, real time fMRI, and diffusion tensor imaging. Additionally, a few empirical studies directly examined brain-based mechanisms of change, whereas others examined brain-based indicators as predictors of treatment outcome. Finally, two commentaries discuss craving as a core feature of addiction, and the importance of a developmental approach to examining mechanisms of change. Ultimately, translational research on mechanisms of behavior change holds promise for increasing understanding of how psychotherapy may modify brain structure and functioning and facilitate the initiation and maintenance of positive treatment outcomes for addictive behaviors. PMID:23815447

Global mental health and neuroscience: potential synergies.

PubMed

Stein, Dan J; He, Yanling; Phillips, Anthony; Sahakian, Barbara J; Williams, John; Patel, Vikram

2015-02-01

Global mental health has emerged as an important specialty. It has drawn attention to the burden of mental illness and to the relative gap in mental health research and services around the world. Global mental health has raised the question of whether this gap is a developmental issue, a health issue, a human rights issue, or a combination of these issues-and it has raised awareness of the need to develop new approaches for building capacity, mobilising resources, and closing the research and treatment gap. Translational neuroscience has also advanced. It comprises an important conceptual approach to understanding the neurocircuitry and molecular basis of mental disorders, to rethinking how best to undertake research on the aetiology, assessment, and treatment of these disorders, with the ultimate aim to develop entirely new approaches to prevention and intervention. Some apparent contrasts exist between these fields; global mental health emphasises knowledge translation, moving away from the bedside to a focus on health systems, whereas translational neuroscience emphasises molecular neuroscience, focusing on transitions between the bench and bedside. Meanwhile, important opportunities exist for synergy between the two paradigms, to ensure that present opportunities in mental health research and services are maximised. Here, we review the approaches of global mental health and clinical neuroscience to diagnosis, pathogenesis, and intervention, and make recommendations for facilitating an integration of these two perspectives. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of two-transsacral-screw fixation versus triangular osteosynthesis for transforaminal sacral fractures.

PubMed

Min, Kyong S; Zamorano, David P; Wahba, George M; Garcia, Ivan; Bhatia, Nitin; Lee, Thay Q

2014-09-01

Transforaminal pelvic fractures are high-energy injuries that are translationally and rotationally unstable. This study compared the biomechanical stability of triangular osteosynthesis vs 2-transsacral-screw fixation in the repair of a transforaminal pelvic fracture model. A transforaminal fracture model was created in 10 cadaveric lumbopelvic specimens. Five of the specimens were stabilized with triangular osteosynthesis, which consisted of unilateral L5-to-ilium lumbopelvic fixation and ipsilateral iliosacral screw fixation. The remaining 5 were stabilized with a 2-transsacral-screw fixation technique that consisted of 2 transsacral screws inserted across S1. All specimens were loaded cyclically and then loaded to failure. Translation and rotation were measured using the MicroScribe 3D digitizing system (Revware Inc, Raleigh, North Carolina). The 2-transsacral-screw group showed significantly greater stiffness than the triangular osteosynthesis group (2-transsacral-screw group, 248.7 N/mm [standard deviation, 73.9]; triangular osteosynthesis group, 125.0 N/mm [standard deviation, 66.9]; P=.02); however, ultimate load and rotational stiffness were not statistically significant. Compared with triangular osteosynthesis fixation, the use of 2 transsacral screws provides a comparable biomechanical stability profile in both translation and rotation. This newly revised 2-transsacral-screw construct offers the traumatologist an alternative method of repair for vertical shear fractures that provides biplanar stability. It also offers the advantage of percutaneous placement in either the prone or supine position. Copyright 2014, SLACK Incorporated.

Link Adaptation for Mitigating Earth-To-Space Propagation Effects on the NASA SCaN Testbed

NASA Technical Reports Server (NTRS)

Kilcoyne, Deirdre K.; Headley, William C.; Leffke, Zach J.; Rowe, Sonya A.; Mortensen, Dale J.; Reinhart, Richard C.; McGwier, Robert W.

2016-01-01

In Earth-to-Space communications, well-known propagation effects such as path loss and atmospheric loss can lead to fluctuations in the strength of the communications link between a satellite and its ground station. Additionally, the typically unconsidered effect of shadowing due to the geometry of the satellite and its solar panels can also lead to link degradation. As a result of these anticipated channel impairments, NASA's communication links have been traditionally designed to handle the worst-case impact of these effects through high link margins and static, lower rate, modulation formats. The work presented in this paper aims to relax these constraints by providing an improved trade-off between data rate and link margin through utilizing link adaptation. More specifically, this work provides a simulation study on the propagation effects impacting NASA's SCaN Testbed flight software-defined radio (SDR) as well as proposes a link adaptation algorithm that varies the modulation format of a communications link as its signal-to-noise ratio fluctuates. Ultimately, the models developed in this work will be utilized to conduct real-time flight experiments on-board the NASA SCaN Testbed.

Detection limits of intraoperative near infrared imaging for tumor resection.

PubMed

Thurber, Greg M; Figueiredo, Jose-Luiz; Weissleder, Ralph

2010-12-01

The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade-offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation. Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds. Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3-5  mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens. A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real-time feedback to obtain clean margins. © 2010 Wiley-Liss, Inc.

Status or subjugation? women, migration and development in the South Pacific.

PubMed

Connell, J

1984-01-01

Similar to the situation elsewhere in the world, migration may enhance a women's position in societies in the regions of the South Pacific by prividing them greater autonomy and competence in new skills whether they are themselves immigrants or remain in villages as heads of households when male relatives leave. Or, it can cause them to lose independence and social standing and be extremely subjugated to men especially when they are 'passive' migrants to towns, or through over-dependence or remittances, poor health and welfare when the maintenace of necessary rural economic activities proves excessively demanding or urban incomes are poor. It is apparent from the Highlands of Papua New Guinea that rather different situations may result in seemingly similar areas. The emergence of cash cropping, wage labor, migration and greater individualism within the nuclear family, as a result of the breakdown of traditional family structures, all emphasize isolation of men and women, and produce conflict, diversity and tension. While women may indeed acquire some elevation in status and prestige from their participation in a greater range of economic, social and political affairs, men too gain in prestige, offsetting women's gains. Pressures on women's time may inhibit their fuller participation in community activities, contributing to their marginalization, and give rise to new economic inequalities despite some gains. Ironically, the type of economic change tends to cause women to be locked into domestic and reproductive roles. Although women have apparently made strides in small South Pacific states, little of this social change is translated into long-term economic changes that would ultimately have a positive impact on the status of women. The lack of absence of proper data concerning women in migration and accompanying phenomena such as changing roles, power structures as well as the changing distribution of resources, virtually ensures the exclusion of women from policy discussions and decisions regarding the provision of appropriate social services and employment opportunities in the sending or receiving country.

Transient Fluvial Response to Alpine Deglaciation, Mount Rainier, WA: Geomorphic Process Domains and Proglacial Flux Controls on Channel Evolution.

NASA Astrophysics Data System (ADS)

Beyeler, J. D.; Montgomery, D.; Kennard, P. M.

2016-12-01

Downwasting of all glaciers on the flanks of Mount Rainier, WA, in recent decades has debuttressed Little Ice Age glaciogenic sediments driving proglacial responses to regionally warming climate. Rivers draining the deglaciating edifice are responding to paraglacial sedimentation processes through transient storage of retreat-liberated sediments in aggrading (e.g., >5m) fluvial networks with widening channel corridors (i.e., 50-150%) post-LIA (ca., 1880-1910 locally). We hypothesize that the downstream transmission of proglacial fluxes (i.e., sediment and water) through deglaciating alpine terrain is a two-step geomorphic process. The ice-proximal portion of the proglacial system is dominated by the delivery of high sediment-to-water ratio flows (i.e., hyperconcentrated and debris slurries) and sediment retention by in-channel accumulation (e.g., confined debris fans within channel margins of valley segments) exacerbated by recruitment and accumulation of large wood (e.g., late seral stage conifers), whereas ice-distal fluvial reworking of transient sediment accumulations generates downstream aggradation. Historical Carbon River observations show restricted ice-proximal proglacial aggradation until a mainstem avulsion in 2009 initiated incision into sediment accumulations formed in recent decades, which is translating into aggradation farther down the network. Surficial morphology mapped with GPS, exposed subsurface sedimentology, and preliminary dating of buried trees suggest a transitional geomorphic process zone has persisted along the proglacial Carbon River through recent centuries and prior to the ultimate LIA glaciation. Structure-from-motion DEM differencing through the 2016 water year shows discrete zones of proglacial evolution through channel-spanning bed aggradation forced by interactions between large wood and sediment-rich flows that transition to fluvial process dominance as sediment is transported downstream. Long-term DEM differencing suggests these are persistent geomorphic processes as rivers respond to alpine deglaciation. This process-based study implies downstream river flooding in deglaciating alpine terrain globally is driven by glaciogenic sediment release and downstream channel aggradation irrespective of changes in discharge.

When mountain belts disrupt mantle flow: from natural evidences to numerical modelling

NASA Astrophysics Data System (ADS)

Yamato, Philippe; Husson, Laurent; Guillaume, Benjamin

2016-04-01

During the Cenozoic, the number of orogens on Earth increased. This observation readily indicates that in the same time, compression in the lithosphere became gradually more and more important. Here, we show that such mountain belts, at plate boundaries, increasingly obstruct plate tectonics, slowing down and reorienting their motions. In turn, it changes the dynamic and kinematic surface conditions of the underlying flowing mantle, which ultimately modifies the pattern of mantle flow. Such forcing could explain many first order features of Cenozoic plate tectonics and mantle flow. Among others, at lithospheric scale, one can cite the compression of passive margins, the important variations in the rates of spreading at oceanic ridges, the initiation of subductions, or the onset of obductions. In the mantle, such changes in boundary conditions redesign the flow pattern and, consequently, disturb the oceanic lithosphere cooling. In order to test this hypothesis we first present thermo-mechanical numerical models of mantle convection above which a lithosphere is resting on top. Our results show that when collision occurs, the mantle flow is strongly modified, which leads to (i) increasing shear stresses below the lithosphere and (ii) a modification of the convection style. In turn, the transition between a "free" convection (mobile lid) and a "disturbed" convection (stagnant - or sluggish - lid) highly impacts the dynamics of the lithosphere at the surface. Thereby, on the basis of these models and a variety of real examples, we show that on the other side of a lithosphere presenting a collision zone, passive margins become squeezed and can undergo compression, which may ultimately evolve into subduction initiation or obduction. We also show that much further, due to the blocking of the lithosphere, spreading rates decrease at the ridge, which may explain a variety of features such as the low magmatism of ultraslow spreading ridges or the departure of slow spreading ridges from the half-space cooling model.

The many impacts of building mountain belts on plate tectonics and mantle flow

NASA Astrophysics Data System (ADS)

Yamato, Philippe; Husson, Laurent

2015-04-01

During the Cenozoic, the number of orogens on Earth increased. This observation readily indicates that in the same time, compression in the lithosphere became gradually more and more important. Such an increase of stresses in the lithosphere can impact on plate tectonics and mantle dynamics. We show that mountain belts at plate boundaries increasingly obstruct plate tectonics, slowing down and reorienting their motions. In turn, this changes the dynamic and kinematic surface conditions of the underlying flowing mantle. Ultimately, this modifies the pattern of mantle flow. This forcing could explain many first order features of Cenozoic plate tectonics and mantle flow. Among these, one can cite the compression of passive margins, the important variations in the rates of spreading at oceanic ridges, or the initiation of subduction, the onset of obduction, for the lithosphere. In the mantle, such change in boundary condition redesigns the pattern of mantle flow and, consequently, the oceanic lithosphere cooling. In order to test this hypothesis we first present thermo-mechanical numerical models of mantle convection above which a lithosphere rests. Our results show that when collision occurs, the mantle flow is highly modified, which leads to (i) increasing shear stresses below the lithosphere and (ii) to a modification of the convection style. In turn, the transition between a 'free' convection (mobile lid) and an 'upset' convection (stagnant -or sluggish- lid) highly impacts the dynamics of the lithosphere at the surface of the Earth. Thereby, on the basis of these models and a variety of real examples, we show that on the other side of a collision zone, passive margins become squeezed and can undergo compression, which may ultimately evolve into subduction or obduction. We also show that much further, due to the blocking of the lithosphere, spreading rates decrease at the ridge, a fact that may explain a variety of features such as the low magmatism of ultraslow spreading ridges or the departure of slow spreading ridges from the half-space cooling model.

Variability of mass-wasting processes in the tectonically-controlled Calabro Tyrrhenian continental margin (Southern Italy)

NASA Astrophysics Data System (ADS)

Casalbore, D.; Bosman, A.; Casas, D.; Chiocci, F. L.; Martorelli, E.; Ridente, D.

2017-12-01

The recent collection of multibeam bathymetry and single-channel seismic profiles on the Calabro-Tyrrhenian continental margin in Southern Italy allowed us to depict a large suite of mass-wasting processes, ranging from gullies up to shelf-indenting canyon system along with over 400 landslide scars, affecting the 52% of the entire area. In detail, slide scars occur from the coast down to -1700 m, with mobilized volumes ranging from some hundreds of m3 up to tens of millions of m3. On the whole, they affect an area of >85 km2, being able to mobilize approximately 1.4 km3. These slides also show a large variability of features both in the headwall, translational and toe domain, thus providing useful insights for a better understanding of their failure and post-failure behavior. The aim of this study is to show the magnitude-frequency relationship of this large amount of slides in order to quantify a range of probabilities for the occurrence of new landslide events as well as to illustrate the main mechanisms that control their development and emplacement.

Benthic foraminiferal assemblage formation: Theory and observation for the European Arctic margin

NASA Astrophysics Data System (ADS)

Loubere, Paul; Rayray, Shan

2016-09-01

We use theory and observation to determine how benthic foraminiferal populations living in a range of sedimentary microenvironments are translated into fossil assemblages along the continental margin of the European Arctic. We examine downcore stained (cell tracker green and rose Bengal) and total species shell abundances through the sediment mixing (bioturbation) zone. This, in combination with porewater geochemical measurements, allows us to establish zones of production and destruction for species' shells, and deduce how the fossil record is being generated by the living community. For many taxa, shell production is high in the upper, oxic, sedimentary layer, but destruction in this zone is also high. Hence, contribution to the fossil record is biased to more infaunal populations and species. Taxa producing near, or below, the anoxic boundary of the sediments are particularly important to the developing fossil record of the fjord environment. We find that taxon relative and absolute abundances change continuously through the biologically active sediment profile. This has implications for reconstructing paleoenvironments using benthic foraminiferal assemblages, and potentially for the geochemistry of individual fossil taxa.

Benthic foraminiferal assemblage formation: Theory and observation for the European Arctic Margin

NASA Astrophysics Data System (ADS)

Loubere, Paul; Rayray, Shan

2016-07-01

We use theory and observation to determine how benthic foraminiferal populations living in a range of sedimentary microenvironments are translated into fossil assemblages along the continental margin of the European Arctic. We examine downcore stained (cell tracker green and rose Bengal) and total species shell abundances through the sediment mixing (bioturbation) zone. This, in combination with porewater geochemical measurements, allows us to establish zones of production and destruction for species' shells, and deduce how the fossil record is being generated by the living community. For many taxa, shell production is high in the upper, oxic, sedimentary layer, but destruction in this zone is also high. Hence, contribution to the fossil record is biased to more infaunal populations and species. Taxa producing near, or below, the anoxic boundary of the sediments are particularly important to the developing fossil record of the fjord environment. We find that taxon relative and absolute abundances change continuously through the biologically active sediment profile. This has implications for reconstructing paleoenvironments using benthic foraminiferal assemblages, and potentially for the geochemistry of individual fossil taxa.

Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

PubMed Central

Rodriguez, Isaac A.; Growney Kalaf, Emily A.; Bowlin, Gary L.; Sell, Scott A.

2014-01-01

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use. PMID:25050347

In Silico Augmentation of the Drug Development Pipeline: Examples from the study of Acute Inflammation

PubMed Central

An, Gary; Bartels, John; Vodovotz, Yoram

2011-01-01

The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high-throughput and –content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are utilized in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. In this article, we present a Translational Systems Biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism. PMID:21552346

Perspectives from the Third International Summit on Medical Nutrition Education and Research

PubMed Central

Crowley, Jennifer Jean; Laur, Celia; Carter, Harrison David Edward; Jones, Glenys; Ray, Sumantra

2018-01-01

Nutrition is an important component of public health and health care, including in education and research, and in the areas of policy and practice. This statement was the overarching message during the third annual International Summit on Medical Nutrition Education and Research, held at Wolfson College, University of Cambridge, United Kingdom, in August 2017. This summit encouraged attendees to think more broadly about the impact of nutrition policy on health and communities, including the need to visualize the complete food system from “pre-farm to post-fork.” Evidence of health issues related to food and nutrition were presented, including the need for translation of knowledge into policy and practice. Methods for this translation included the use of implementation and behavior change techniques, recognizing the needs of health-care professionals, policy makers, and the public. In all areas of nutrition and health, clear and effective messages, supported by open data, information, and actionable knowledge, are also needed along with strong measures of impact centered on an ultimate goal: to improve nutritional health and wellbeing for patients and the public. PMID:29629367

Profiling of Histone Post-Translational Modifications in Mouse Brain with High-Resolution Top-Down Mass Spectrometry.

PubMed

Zhou, Mowei; Paša-Tolić, Ljiljana; Stenoien, David L

2017-02-03

As histones play central roles in most chromosomal functions including regulation of DNA replication, DNA damage repair, and gene transcription, both their basic biology and their roles in disease development have been the subject of intense study. Because multiple post-translational modifications (PTMs) along the entire protein sequence are potential regulators of histones, a top-down approach, where intact proteins are analyzed, is ultimately required for complete characterization of proteoforms. However, significant challenges remain for top-down histone analysis primarily because of deficiencies in separation/resolving power and effective identification algorithms. Here we used state-of-the-art mass spectrometry and a bioinformatics workflow for targeted data analysis and visualization. The workflow uses ProMex for intact mass deconvolution, MSPathFinder as a search engine, and LcMsSpectator as a data visualization tool. When complemented with the open-modification tool TopPIC, this workflow enabled identification of novel histone PTMs including tyrosine bromination on histone H4 and H2A, H3 glutathionylation, and mapping of conventional PTMs along the entire protein for many histone subunits.

The mindedness of maternal touch: An investigation of maternal mind-mindedness and mother-infant touch interactions.

PubMed

Crucianelli, Laura; Wheatley, Lisa; Filippetti, Maria Laura; Jenkinson, Paul M; Kirk, Elizabeth; Fotopoulou, Aikaterini Katerina

2018-01-31

Increasing evidence shows that maternal touch may promote emotion regulation in infants, however less is known about how parental higher-order social cognition abilities are translated into tactile, affect-regulatory behaviours towards their infants. During 10 min book-reading, mother-infant sessions when infants were 12 months old (N = 45), we investigated maternal mind-mindedness (MM), the social cognitive ability to understand an infant's mental state, by coding the contingency of maternal verbal statements towards the infants' needs and desires. We also rated spontaneous tactile interactions in terms of their emotional contingency. We found that frequent non-attuned mind-related comments were associated with touch behaviours that were not contingent with the infant's emotions; ultimately discouraging affective tactile responses from the infant. However, comments that were more appropriate to infant's mental states did not necessarily predict more emotionally-contingent tactile behaviours. These findings suggest that when parental high-order social cognitive abilities are compromised, they are also likely to translate into inappropriate, tactile attempts to regulate infant's emotions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Perspectives from the Third International Summit on Medical Nutrition Education and Research.

PubMed

Crowley, Jennifer Jean; Laur, Celia; Carter, Harrison David Edward; Jones, Glenys; Ray, Sumantra

2018-01-01

Nutrition is an important component of public health and health care, including in education and research, and in the areas of policy and practice. This statement was the overarching message during the third annual International Summit on Medical Nutrition Education and Research, held at Wolfson College, University of Cambridge, United Kingdom, in August 2017. This summit encouraged attendees to think more broadly about the impact of nutrition policy on health and communities, including the need to visualize the complete food system from "pre-farm to post-fork." Evidence of health issues related to food and nutrition were presented, including the need for translation of knowledge into policy and practice. Methods for this translation included the use of implementation and behavior change techniques, recognizing the needs of health-care professionals, policy makers, and the public. In all areas of nutrition and health, clear and effective messages, supported by open data, information, and actionable knowledge, are also needed along with strong measures of impact centered on an ultimate goal: to improve nutritional health and wellbeing for patients and the public.

Mutual Distrust: Perspectives From Researchers and Policy Makers on the Research to Policy Gap in 2013 and Recommendations for the Future

PubMed Central

Gollust, Sarah E.; Seymour, Jane W.; Pany, Maximilian J.; Goss, Adeline; Meisel, Zachary F.; Grande, David

2017-01-01

The production of health policy-relevant research is necessary, but not sufficient, to promote its utilization in policy. Our objective was to understand the perspectives of United States’ state-level policy makers and health researchers on the barriers and facilitators to the translation of health evidence into the policy process, with a particular focus on issues related to relationship building. We conducted interviews with 215 US health services and health policy researchers and 40 state-level staffers and legislators. Researchers and policy makers faced the same major barrier to research translation: lack of dedicated time to do so. Some policy makers questioned the credibility of research, and researchers questioned policy makers’ authentic desire to use evidence in decision making. For some study participants, a mutual mistrust of the other group challenges stronger relationship formation. Interventions are needed to help both groups understand a broader role that research plays in policy making and to increase personal contact, and ultimately trusted relationships, across various actors in the policy process. PMID:28452251

Translating Big Data into Smart Data for Veterinary Epidemiology

PubMed Central

VanderWaal, Kimberly; Morrison, Robert B.; Neuhauser, Claudia; Vilalta, Carles; Perez, Andres M.

2017-01-01

The increasing availability and complexity of data has led to new opportunities and challenges in veterinary epidemiology around how to translate abundant, diverse, and rapidly growing “big” data into meaningful insights for animal health. Big data analytics are used to understand health risks and minimize the impact of adverse animal health issues through identifying high-risk populations, combining data or processes acting at multiple scales through epidemiological modeling approaches, and harnessing high velocity data to monitor animal health trends and detect emerging health threats. The advent of big data requires the incorporation of new skills into veterinary epidemiology training, including, for example, machine learning and coding, to prepare a new generation of scientists and practitioners to engage with big data. Establishing pipelines to analyze big data in near real-time is the next step for progressing from simply having “big data” to create “smart data,” with the objective of improving understanding of health risks, effectiveness of management and policy decisions, and ultimately preventing or at least minimizing the impact of adverse animal health issues. PMID:28770216

Aβ1-42 triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons.

PubMed

Walker, Chandler A; Randolph, Lisa K; Matute, Carlos; Alberdi, Elena; Baleriola, Jimena; Hengst, Ulrich

2018-05-14

Neurons frequently encounter neurodegenerative signals first in their periphery. For example, exposure of axons to oligomeric Aβ 1-42 is sufficient to induce changes in the neuronal cell body that ultimately lead to degeneration. Currently, it is unclear how the information about the neurodegenerative insult is transmitted to the soma. Here, we find that the translation of pre-localized but normally silenced sentinel mRNAs in axons is induced within minutes of Aβ 1-42 addition in a Ca 2+ -dependent manner. This immediate protein synthesis following Aβ 1-42 exposure generates a retrograde signaling complex including vimentin. Inhibition of the immediate protein synthesis, knock-down of axonal vimentin synthesis, or inhibition of dynein-dependent transport to the soma prevented the normal cell body response to Aβ 1-42 These results establish that CNS axons react to neurodegenerative insults via the local translation of sentinel mRNAs encoding components of a retrograde signaling complex that transmit the information about the event to the neuronal soma. © 2018 The Authors.

Advancing research in regeneration and repair of the motor circuitry: non-human primate models and imaging scales as the missing links for successfully translating injectable therapeutics to the clinic.

PubMed

Tsintou, Magdalini; Dalamagkas, Kyriakos; Makris, Nikos

2016-01-01

Regeneration and repair is the ultimate goal of therapeutics in trauma of the central nervous system (CNS). Stroke and spinal cord injury (SCI) are two highly prevalent CNS disorders that remain incurable, despite numerous research studies and the clinical need for effective treatments. Neural engineering is a diverse biomedical field, that addresses these diseases using new approaches. Research in the field involves principally rodent models and biologically active, biodegradable hydrogels. Promising results have been reported in preclinical studies of CNS repair, demonstrating the great potential for the development of new treatments for the brain, spinal cord and peripheral nerve injury. Several obstacles stand in the way of clinical translation of neuroregeneration research. There seems to be a key gap in the translation of research from rodent models to human applications, namely non-human primate models, which constitute a critical bridging step. Applying injectable therapeutics and multimodal neuroimaging in stroke lesions using experimental rhesus monkey models is an avenue that a few research groups have begun to embark on. Understanding and assessing the changes that the injured brain or spinal cord undergoes after an intervention with biodegradable hydrogels in non-human primates seem to represent critical preclinical research steps. Existing innovative models in non-human primates allow us to evaluate the potential of neural engineering and injectable hydrogels. The results of these preliminary studies will pave the way for translating this research into much needed clinical therapeutic approaches. Cutting edge imaging technology using Connectome scanners represents a tremendous advancement, enabling the in vivo, detailed, high-resolution evaluation of these therapeutic interventions in experimental animals. Most importantly, they also allow quantifiable and clinically meaningful correlations with humans, increasing the translatability of these innovations to the bedside.

Biomechanical Comparison of an Intramedullary and Extramedullary Free-Tissue Graft Reconstruction of the Acromioclavicular Joint Complex

PubMed Central

Garg, Rishi; Javidan, Pooya; Lee, Thay Q.

2013-01-01

Background Several different surgical techniques have been described to address the coracoclavicular (CC) ligaments in acromioclavicular (AC) joint injuries. However, very few techniques focus on reconstructing the AC ligaments, despite its importance in providing stability. The purpose of our study was to compare the biomechanical properties of two free-tissue graft techniques that reconstruct both the AC and CC ligaments in cadaveric shoulders, one with an extramedullary AC reconstruction and the other with an intramedullary AC reconstruction. We hypothesized intramedullary AC reconstruction will provide greater anteroposterior translational stability and improved load to failure characteristics than an extramedullary technique. Methods Six matched cadaveric shoulders underwent translational testing at 10 N and 15 N in the anteroposterior and superoinferior directions, under AC joint compression loads of 10 N, 20 N, and 30 N. After the AC and CC ligaments were transected, one of the specimens was randomly assigned the intramedullary free-tissue graft reconstruction while its matched pair received the extramedullary graft reconstruction. Both reconstructed specimens then underwent repeat translational testing, followed by load to failure testing, via superior clavicle distraction, at a rate of 50 mm/min. Results Intramedullary reconstruction provided significantly greater translational stability in the anteroposterior direction than the extramedullary technique for four of six loading conditions (p < 0.05). There were no significant differences in translational stability in the superoinferior direction for any loading condition. The intramedullary reconstructed specimens demonstrated improved load to failure characteristics with the intramedullary reconstruction having a lower deformation at yield and a higher ultimate load than the extramedullary reconstruction (p < 0.05). Conclusions Intramedullary reconstruction of the AC joint provides greater stability in the anteroposterior direction and improved load to failure characteristics than an extramedullary technique. Reconstruction of the injured AC joint with an intramedullary free tissue graft may provide greater strength and stability than other currently used techniques, allowing patients to have improved clinical outcomes. PMID:24340150

The new genetic technologies: why a theological perspective is necessary.

PubMed

Engelhardt, H Tristram

2003-01-01

Secular bioethics poses questions that can be recognized as important, though it lacks the resources to answer them. Secular bioethics may retain the sense that there should be moral limits to the use of germline genetic engineering, but it lacks the basis to justify limits in principle. The contemporary practice of bioethics arose in the United States to fill a moral vacuum created by (1) the marginalization of medical ethics through the deprofessionalization of medicine, (2) the secularization of American society, and (3) an increased reliance on individual decision-making. The result is an ethics at the core of secular bioethics severed from a sense of ultimate purpose or direction for humans or the cosmos. This ethics and its bioethics are marked by (1) moral fragmentation and pluralism and (2) a loss of ultimate orientation. This bioethics can at best require (1) the prudent maximization of benefits over harms, (2) the condemnation of malevolent acts, and (3) the use of persons only with their consent. However, there fails to be a basis for a common view of benefit or of harm. Within this impoverished moral context, human biological nature can only appear to be a contingent outcome of spontaneous mutations, selective pressure, the constraints of physical laws, and random catastrophes. Such a bioethics, deprived of ultimate orientation, can provide no ground in principle for forbidding cloning, germline genetic engineering, or the fundamental recasting of human nature. Absent a theological point of orientation, medicine and the genetic technology are left with more power than ever but no clear moral sense of how to use that power.

Preparing clinical pharmacy scientists for careers in clinical/translational research: can we meet the challenge?: ACCP Research Affairs Committee Commentary.

PubMed

Parker, Robert B; Ellingrod, Vicki; DiPiro, Joseph T; Bauman, Jerry L; Blouin, Robert A; Welage, Lynda S

2013-12-01

Developing clinical pharmacists' research skills and their ability to compete for extramural funding is an important component of the American College of Clinical Pharmacy's (ACCP) vision for pharmacists to play a prominent role in generating the new knowledge used to guide patient pharmacotherapy. Given the recent emphasis on clinical/translational research at the National Institutes of Health (NIH) and the key role of drug therapy in the management of many diseases, there is an unprecedented opportunity for the profession to contribute to this enterprise. A crucial question facing the profession is whether we can generate enough appropriately trained scientists to take advantage of these opportunities to generate the new knowledge to advance drug therapy. Since the 2009 publication of the ACCP Research Affairs Committee editorial recommending the Ph.D. degree (as opposed to fellowship training) as the optimal method for preparing pharmacists as clinical/translational scientists, significant changes have occurred in the economic, professional, political, and research environments. As a result, the 2012 ACCP Research Affairs Committee was charged with reexamining the college's position on training clinical pharmacy scientists in the context of these substantial environmental changes. In this commentary, the potential impact of these changes on opportunities for pharmacists in clinical/translational research are discussed as are strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. Failure of our profession to take advantage of these opportunities risks our ability to contribute substantively to the biomedical research enterprise and ultimately improve the pharmacotherapy of our patients. © 2013 Pharmacotherapy Publications, Inc.

Approaches to preparing young scholars for careers in interdisciplinary team science.

PubMed

Begg, Melissa D; Crumley, Gene; Fair, Alecia M; Martina, Camille A; McCormack, Wayne T; Merchant, Carol; Patino-Sutton, Cecilia M; Umans, Jason G

2014-01-01

To succeed as a biomedical researcher, the ability to flourish in interdisciplinary teams of scientists is becoming ever more important. Institutions supported by the Clinical and Translational Science Awards (CTSAs) from the National Institutes of Health have a specific mandate to educate the next generation of clinical and translational researchers. While they strive to advance integrated and interdisciplinary approaches to education and career development in clinical and translational science, general approaches and evaluation strategies may differ, as there is no single, universally accepted or standardized approach. It is important, therefore, to learn about the different approaches used to determine what is effective. We implemented a Web-based survey distributed to education leaders at the 60 funded CTSA institutions; 95% responded to the survey, which included questions on the importance of preparation for interdisciplinary team science careers, methods used to provide such training, and perceived effectiveness of these training programs. The vast majority (86%) of education leaders reported that such training is important, and about half (52%) of the institutions offer such training. Methods of training most often take the form of courses and seminars, both credit bearing and noncredit. These efforts are, by and large, perceived as effective by the training program leaders, although long-term follow-up of trainees would be required to fully evaluate ultimate effectiveness. Results from the survey suggest that CTSA education directors believe that specific training in interdisciplinary team science for young investigators is very important, but few methodologies are universally practiced in CTSA institutions to provide training or to assess performance. Four specific recommendations are suggested to provide measurable strategic goals for education in team science in the context of clinical and translational research.

Networks of Collaboration among Scientists in a Center for Diabetes Translation Research

PubMed Central

Harris, Jenine K.; Wong, Roger; Thompson, Kellie; Haire-Joshu, Debra; Hipp, J. Aaron

2015-01-01

Background Transdisciplinary collaboration is essential in addressing the translation gap between scientific discovery and delivery of evidence-based interventions to prevent and treat diabetes. We examined patterns of collaboration among scientists at the Washington University Center for Diabetes Translation Research. Methods Members (n = 56) of the Washington University Center for Diabetes Translation Research were surveyed about collaboration overall and on publications, presentations, and grants; 87.5% responded (n = 49). We used traditional and network descriptive statistics and visualization to examine the networks and exponential random graph modeling to identify predictors of collaboration. Results The 56 network members represented nine disciplines. On average, network members had been affiliated with the center for 3.86 years (s.d. = 1.41). The director was by far the most central in all networks. The overall and publication networks were the densest, while the overall and grant networks were the most centralized. The grant network was the most transdisciplinary. The presentation network was the least dense, least centralized, and least transdisciplinary. For every year of center affiliation, network members were 10% more likely to collaborate (OR: 1.10; 95% CI: 1.00–1.21) and 13% more likely to write a paper together (OR: 1.13; 95% CI: 1.02–1.25). Network members in the same discipline were over twice as likely to collaborate in the overall network (OR: 2.10; 95% CI: 1.40–3.15); however, discipline was not associated with collaboration in the other networks. Rank was not associated with collaboration in any network. Conclusions As transdisciplinary centers become more common, it is important to identify structural features, such as a central leader and ongoing collaboration over time, associated with scholarly productivity and, ultimately, with advancing science and practice. PMID:26301873

Networks of Collaboration among Scientists in a Center for Diabetes Translation Research.

PubMed

Harris, Jenine K; Wong, Roger; Thompson, Kellie; Haire-Joshu, Debra; Hipp, J Aaron

2015-01-01

Transdisciplinary collaboration is essential in addressing the translation gap between scientific discovery and delivery of evidence-based interventions to prevent and treat diabetes. We examined patterns of collaboration among scientists at the Washington University Center for Diabetes Translation Research. Members (n = 56) of the Washington University Center for Diabetes Translation Research were surveyed about collaboration overall and on publications, presentations, and grants; 87.5% responded (n = 49). We used traditional and network descriptive statistics and visualization to examine the networks and exponential random graph modeling to identify predictors of collaboration. The 56 network members represented nine disciplines. On average, network members had been affiliated with the center for 3.86 years (s.d. = 1.41). The director was by far the most central in all networks. The overall and publication networks were the densest, while the overall and grant networks were the most centralized. The grant network was the most transdisciplinary. The presentation network was the least dense, least centralized, and least transdisciplinary. For every year of center affiliation, network members were 10% more likely to collaborate (OR: 1.10; 95% CI: 1.00-1.21) and 13% more likely to write a paper together (OR: 1.13; 95% CI: 1.02-1.25). Network members in the same discipline were over twice as likely to collaborate in the overall network (OR: 2.10; 95% CI: 1.40-3.15); however, discipline was not associated with collaboration in the other networks. Rank was not associated with collaboration in any network. As transdisciplinary centers become more common, it is important to identify structural features, such as a central leader and ongoing collaboration over time, associated with scholarly productivity and, ultimately, with advancing science and practice.

Kinematic development of the Tibetan Plateau's northern margin: A traverse across the Qilian Shan-Nan Shan thrust belt

NASA Astrophysics Data System (ADS)

Zuza, A. V.; Levy, D. A.; Wang, Z.; Xiong, X.; Chen, X.

2017-12-01

The active Cenozoic Qilian Shan-Nan Shan thrust belt defines the northern margin of the Tibetan Plateau. The kinematic development of this thrust belt has implications models of plateau growth and Himalayan-Tibetan orogen strain accommodation. We present new field observations and analytical data from a traverse across the 350-km-wide doubly vergent Qilian Shan, which is bound by the south-dipping North Qilian thrust system in the north and the north-dipping range-bounding Qinghai Nanshan-Dulan Shan thrust system in the south. These faults, and several other major thrusts within the thrust-belt interior, disrupt relatively thick Oligocene-Miocene basin deposits. Of note, many of the thrust faults across the width of the Qilian Shan have Quaternary fault scarps, indicating that active deformation is distributed and not only concentrated along the northern frontal faults. By integrating our detailed structural traverse with new geophysical observations and thermochronology data across the northern plateau margin, we construct a kinematic model for the development of the Tibetan Plateau's northern margin. Deformation initiated in the Eocene-Oligocene along the north-dipping Qinghai Nanshan-Dulan Shan and south-dipping Tuolai Nan Shan thrusts, the latter of which then defined the northern boundary of the Tibetan Plateau. This early deformation was focused along preexisting early Paleozoic structures. A 200-km-wide basin formed between these ranges, and from the Miocene to present, new thrust- and strike-slip-fault-bounded ranges developed, including the north-directed North Qilian and the south-directed Tuolai Nan thrusts. Thus, our observations do not support northward propagating thrust-belt expansion. Instead, we envision that the initial thrust-belt development generated a wide Oligocene-Miocene north-plateau basin that was subsequently disintegrated by later Miocene to present thrusting and strike-slip faulting. Ultimately, the Qilian Shan-Nan Shan thrust belt differs from a typical orogenic thrust wedge, and active deformation is distributed across the range.

Does serpentinite carbonation occur during recharge or discharge of hydrothermal fluids? A case of study from the Newfoundland margin

NASA Astrophysics Data System (ADS)

Picazo, Suzanne; Malvoisin, Benjamin; Baumgartner, Lukas P.; Bouvier, Anne-Sophie

2017-04-01

Hydrothermal fluid circulation in extensional systems occurrs along the spreading axis of passive, hyper-extended margins and mid-ocean ridges. The most studied feature resulting from hydrothermal circulation is the sub-seafloor chimneys because of their accessibility. Here we focus on the less studied carbonation process of the associated serpentinites. Carbonation of partially to totally serpentinized peridotite i.e. peridotite/serpentinite replacement by carbonate is usually described as a process of veining or matrix formation but not direct replacement of serpentinite. Carbonates that crystallize in veins or as a matrix in a sedimentary setting is known in near-surface environments like Oman (Kelemen et al, 2011), however the processes and timing of carbonation are still not well understood. This study is examins in detail the onset of carbonation in the footwall of the detachment faults responsible for mantle exhumation in hyper-extended rifted margins. It is based on drilled samples from ODP Leg 210 Site 1277 in the Newfoundland margin. We observed calcite grains in the mesh core replacing serpentine and we measured δ18O from core to rim of the calcite grain using the Secondary Ion Mass Spectrometer (SIMS, SwissSIMS facility, University of Lausanne). Ultimately δ18O measurements lead us to infer the temperature of calcite growth. We suplement the study with equilibrium thermodynamic modeling in an open system where fluid can be transported either upwards or downwards. The model allows us determining the influence of fluid flow direction, temperature, pressure and fluid/rock ratio on the stability of carbonates and serpentine, and thus to discuss if carbonation occurs during recharge or discharge of the fluids. Kelemen, P. B., Matter, J., Streit, E. E., Rudge, J. F., Curry, W. B., & Blusztajn, J. (2011). Rates and mechanisms of mineral carbonation in peridotite: natural processes and recipes for enhanced, in situ CO2 capture and storage. Annual Review of Earth and Planetary Sciences, 39, 545-576.

Impact of structural and autocyclic basin-floor topography on the depositional evolution of the deep-water Valparaiso forearc basin, central Chile

USGS Publications Warehouse

Laursen, J.; Normark, W.R.

2003-01-01

The Valparaiso Basin constitutes a unique and prominent deep-water forearc basin underlying a 40-km by 60-km mid-slope terrace at 2.5-km water depth on the central Chile margin. Seismic-reflection data, collected as part of the CONDOR investigation, image a 3-3.5-km thick sediment succession that fills a smoothly sagged, margin-parallel, elongated trough at the base of the upper slope. In response to underthrusting of the Juan Ferna??ndez Ridge on the Nazca plate, the basin fill is increasingly deformed in the seaward direction above seaward-vergent outer forearc compressional highs. Syn-depositional growth of a large, margin-parallel monoclinal high in conjunction with sagging of the inner trough of the basin created stratal geometries similar to those observed in forearc basins bordered by large accretionary prisms. Margin-parallel compressional ridges diverted turbidity currents along the basin axis and exerted a direct control on sediment depositional processes. As structural depressions became buried, transverse input from point sources on the adjacent upper slope formed complex fan systems with sediment waves characterising the overbank environment, common on many Pleistocene turbidite systems. Mass failure as a result of local topographic inversion formed a prominent mass-flow deposit, and ultimately resulted in canyon formation and hence a new focused point source feeding the basin. The Valparaiso Basin is presently filled to the spill point of the outer forearc highs, causing headward erosion of incipient canyons into the basin fill and allowing bypass of sediment to the Chile Trench. Age estimates that are constrained by subduction-related syn-depositional deformation of the upper 700-800m of the basin fill suggest that glacio-eustatic sea-level lowstands, in conjunction with accelerated denudation rates, within the past 350 ka may have contributed to the increase in simultaneously active point sources along the upper slope as well as an increased complexity of proximal depositional facies.

Online Classroom Research and Analysis Activities Using MARGINS-Related Resources for the Izu-Bonin-Mariana Subduction System

NASA Astrophysics Data System (ADS)

Ryan, J. G.

2007-12-01

Students today have online access to nearly unlimited scientific information in an entirely unfiltered state. As such, they need guidance and training in identifying and assessing high-quality information resources for educational and research use. The extensive research data resources available online for the Izu-Bonin-Mariana (IBM) subduction system that have been developed with MARGINS Program and related NSF funding are an ideal venue for focused Web research exercises that can be tailored to a range of undergraduate geoscience courses. This presentation highlights student web research activities examining: a) The 2003-2005 eruptions of Anatahan Volcano in the Mariana volcanic arc. MARGINS-supported geophysical research teams were in the region when the eruption initiated, permitting a unique "event response" data collection and analysis process, with preliminary results presented online at websites linked to the MARGINS homepage, and ultimately published in a special issue of the Journal of Volcanology and Geothermal Research. In this activity, students will conduct a directed Web surf/search effort for information on and datasets from the Anatahan arc volcano, which they will use in an interpretive study of recent magmatic activity in the Mariana arc. This activity is designed as a homework exercise for use in a junior-senior level Petrology course, but could easily be taken into greater depth for the benefit of graduate-level volcanology or geochemistry offerings. b) Geochemical and mineralogical results from ODP Legs 125 and 195 focused on diapiric serpentinite mud volcanoes, which erupt cold, high pH fluids, serpentine muds, and serpentinized ultramafic clasts at a number of sites in the forearc region of the Mariana subduction zone. The focus of this activity is an examination of the trace element chemistry of the forearc serpentines and their associated upwelling porefluids as a means of understanding the roles of ionic radius, valence, and system abundance in the formation and trace element systematics of serpentine group minerals.

Population genomics and geographical parthenogenesis in Japanese harvestmen (Opiliones, Sclerosomatidae, Leiobunum).

PubMed

Burns, Mercedes; Hedin, Marshal; Tsurusaki, Nobuo

2018-01-01

Naturally occurring population variation in reproductive mode presents an opportunity for researchers to test hypotheses regarding the evolution of sex. Asexual reproduction frequently assumes a geographical pattern, in which parthenogenesis-dominated populations are more broadly dispersed than their sexual conspecifics. We evaluate the geographical distribution of genomic signatures associated with parthenogenesis using nuclear and mitochondrial DNA sequence data from two Japanese harvestman sister taxa, Leiobunum manubriatum and Leiobunum globosum . Asexual reproduction is putatively facultative in these species, and female-biased localities are common in habitat margins. Past karyotypic and current cytometric work indicates L. globosum is entirely tetraploid, while L. manubriatum may be either diploid or tetraploid. We estimated species phylogeny, genetic differentiation, diversity, and mitonuclear discordance in females collected across the species range in order to identify range expansion toward marginal habitat, potential for hybrid origin, and persistence of asexual lineages. Our results point to northward expansion of a tetraploid ancestor of L. manubriatum and L. globosum , coupled with support for greater male gene flow in southern L. manubriatum localities. Specimens from localities in the Tohoku and Hokkaido regions were indistinct, particularly those of L. globosum , potentially due to little mitochondrial differentiation or haplotypic variation. Although L. manubriatum overlaps with L. globosum across its entire range, L. globosum was reconstructed as monophyletic with strong support using mtDNA, and marginal support with nuclear loci. Ultimately, we find evidence for continued sexual reproduction in both species and describe opportunities to clarify the rate and mechanism of parthenogenesis.

SELF-ORGANIZATION OF RECONNECTING PLASMAS TO MARGINAL COLLISIONALITY IN THE SOLAR CORONA

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

Imada, S.; Zweibel, E. G.

We explore the suggestions by Uzdensky and Cassak et al. that coronal loops heated by magnetic reconnection should self-organize to a state of marginal collisionality. We discuss their model of coronal loop dynamics with a one-dimensional hydrodynamic calculation. We assume that many current sheets are present, with a distribution of thicknesses, but that only current sheets thinner than the ion skin depth can rapidly reconnect. This assumption naturally causes a density-dependent heating rate which is actively regulated by the plasma. We report nine numerical simulation results of coronal loop hydrodynamics in which the absolute values of the heating rates aremore » different but their density dependences are the same. We find two regimes of behavior, depending on the amplitude of the heating rate. In the case that the amplitude of heating is below a threshold value, the loop is in stable equilibrium. Typically, the upper and less dense part of a coronal loop is collisionlessly heated and conductively cooled. When the amplitude of heating is above the threshold, the conductive flux to the lower atmosphere required to balance collisionless heating drives an evaporative flow which quenches fast reconnection, ultimately cooling and draining the loop until the cycle begins again. The key elements of this cycle are gravity and the density dependence of the heating function. Some additional factors are present, including pressure-driven flows from the loop top, which carry a large enthalpy flux and play an important role in reducing the density. We find that on average the density of the system is close to the marginally collisionless value.« less

Cost-effectiveness of strategies to enhance mammography use.

PubMed

Fishman, P; Taplin, S; Meyer, D; Barlow, W

2000-01-01

To estimate the cost-effectiveness of three strategies to increase breast cancer screening with mammography (reminder postcard, reminder telephone call, and motivational telephone call). Cost accounting for each strategy followed by cost-effectiveness analysis. DATA SOURCE FOR EFFECTIVENESS: Randomized trial of three strategies conducted at Group Health Cooperative of Puget Sound (GHC). Women 50 to 79 years of age who were enrolled in GHC's breast cancer screening program who did not schedule screening mammography within 2 months after it was recommended by letter. Health plan. Marginal cost-effectiveness of each additional woman screened. Because of its high cost (about $26 per call) and intermediate effectiveness, the motivational call was the least cost-effective strategy. If it was assumed that 50% of the women who scheduled mammography after receiving the reminder postcard would have scheduled mammography within 10 months even without it, marginal cost-effectiveness for the postcard among all women was $22 per woman screened versus $92 for the reminder call. Among women with no previous mammography, the marginal cost-effectiveness for the postcard was $70 versus $100 for the reminder call. Among women with no previous mammography, the choice between the reminder postcard and the reminder call was sensitive to assumptions about the percentage of women expected to receive mammography in the absence of other promotional strategies. A simple reminder postcard is the most cost-effective way to increase mammography. Choices about how to promote mammography will ultimately depend on plan values and willingness to invest in promotional strategies that increase participation at higher unit costs.

The chemical and isotopic differentiation of an epizonal magma body: Organ Needle pluton, New Mexico

USGS Publications Warehouse

Verplanck, P.L.; Farmer, G.L.; McCurry, M.; Mertzman, S.A.

1999-01-01

Major and trace element, and Nd and Sr isotopic compositions of whole rocks and mineral separates from the Oligocene, alkaline Organ Needle pluton (ONP), southern New Mexico, constrain models for the differentiation of the magma body parental to this compositionally zoned and layered epizonal intrusive body. The data reveal that the pluton is rimmed by lower ??(Nd) (~-5) and higher 87Sr/86Sr (~0.7085) syenitic rocks than those in its interior (??(Nd) ~ 2, 87Sr/86Sr ~0.7060) and that the bulk compositions of the marginal rocks become more felsic with decreasing structural depth. At the deepest exposed levels of the pluton, the ??(Nd)~-5 lithology is a compositionally heterogeneous inequigranular syenite. Modal, compositional and isotopic data from separates of rare earth element (REE)-bearing major and accesory mineral phases (hornblende, titanite, apatite, zircon) demonstrate that this decoupling of trace and major elements in the inequigranular syenite results from accumulation of light REE (LREE)-bearing minerals that were evidently separated from silicic magmas as the latter rose along the sides of the magma chamber. Chemical and isotopic data for microgranular mafic enclaves, as well as for restite xenoliths of Precambrian granite wall rock, indicate that the isotopic distinction between the marginal and interior facies of the ONP probably reflects assimilation of the wall rock by ??(Nd) ~-2 mafic magmas near the base of the magma system. Fractional crystallization and crystal liquid separation of the crystally contaminated magma at the base and along the margins of the chamber generated the highly silicic magmas that ultimately pooled at the chamber top.

The effect of repair costs on the profitability of a ureteroscopy program.

PubMed

Tosoian, Jeffrey J; Ludwig, Wesley; Sopko, Nikolai; Mullins, Jeffrey K; Matlaga, Brian R

2015-04-01

Ureteroscopy (URS) is a common treatment for patients with stone disease. One of the disadvantages of this approach is the great capital expense associated with the purchase and repair of endoscopic equipment. In some cases, these costs can outpace revenues and lead to an unprofitable and unsustainable enterprise. We sought to characterize the profitability of our URS program when accounting for endoscope maintenance and repair costs. We identified all URS cases performed at a single hospital during fiscal year 2013 (FY2013). Charges, collection rates, and fixed and variable costs including annual equipment repair costs were obtained. The net margin and break-even point of URS were derived on a per-case basis. For 190 cases performed in FY2013, total endoscope repair costs totaled $115,000, resulting in an average repair cost of $605 per case. The vast majority of cases (94.2%) were conducted in the outpatient setting, which generated a net margin of $659 per case, while inpatient cases yielded a net loss of $455. URS was ultimately associated with a net positive margin approaching $600 per case. On break-even analysis, URS remained profitable until repair costs reached $1200 per case. Based on these findings, an established URS program can sustain profitability even with large equipment repair costs. Nonetheless, our findings serve to emphasize the importance of controlling costs, particularly in the current setting of decreasing reimbursement. A multifaceted approach, based on improving endoscope durability and exploring digital and disposable platforms, will be critical in maintaining the sustainability of URS.

Subduction Zone Dewatering at the Southern End of New Zealand's Hikurangi Margin - Insights from 2D Seismic Tomography

NASA Astrophysics Data System (ADS)

Crutchley, G. J.; Klaeschen, D.

2016-12-01

The southern end of New Zealand's Hikurangi subduction margin is characterised by highly-oblique convergence as it makes a southward transition into a right-lateral transform plate boundary. Long-offset seismic data that cross part of the offshore portion of this transition zone give new insight into the nature of the margin. We have carried out two-dimensional pre-stack depth migrations with an iterative reflection tomography to update the velocity field on two seismic lines in this area. The depth-migrated sections show much-improved imaging of faulting within the wedge, and the seismic velocities themselves give clues about the distribution of gas and/or overpressured regions at the plate boundary and within the overlying wedge. A fascinating observation is a major splay fault that has been (or continues to be) a preferred dewatering pathway through the wedge, evidenced by a thermal anomaly that has left its mark on the overlying gas hydrate layer. Another interesting observation is a thick and laterally extensive low velocity zone beneath the subduction interface, which might have important implications for the long-term mechanical stability of the interface. Our on-going work on these data is focused on amplitude versus offset analysis in an attempt to better understand the nature of the subduction interface and also the shallower gas hydrate system. This study is an example of how distinct disturbances of the gas hydrate system can provide insight into subduction zone fluid flow processes that are important for understanding wedge stability and ultimately earthquake hazard.

Analytical electron microscopy in the study of biological systems.

PubMed

Johnson, D E

1986-01-01

The AEM is a powerful tool in biological research, capable of providing information simply not available by other means. The use of a field emission STEM for this application can lead to a significant improvement in spatial resolution in most cases now allowed by the quality of the specimen preparation but perhaps ultimately limited by the effects of radiation damage. Increased elemental sensitivity is at least possible in selected cases with electron energy-loss spectrometry, but fundamental aspects of ELS will probably confine its role to that of a limited complement to EDS. The considerable margin for improvement in sensitivity of the basic analytical technique means that the search for technological improvement will continue. Fortunately, however, current technology can also continue to answer important biological questions.

Investigating Married Adults' Communal Coping with Genetic Health Risk and Perceived Discrimination

PubMed Central

Smith, Rachel A.; Sillars, Alan; Chesnut, Ryan P.; Zhu, Xun

2017-01-01

Increased genetic testing in personalized medicine presents unique challenges for couples, including managing disease risk and potential discrimination as a couple. This study investigated couples' conflicts and support gaps as they coped with perceived genetic discrimination. We also explored the degree to which communal coping was beneficial in reducing support gaps, and ultimately stress. Dyadic analysis of married adults (N = 266, 133 couples), in which one person had the genetic risk for serious illness, showed that perceived discrimination predicted more frequent conflicts about AATD-related treatment, privacy boundaries, and finances, which, in turn, predicted wider gaps in emotion and esteem support, and greater stress for both spouses. Communal coping predicted lower support gaps for both partners and marginally lower stress. PMID:29731540

Investigating Married Adults' Communal Coping with Genetic Health Risk and Perceived Discrimination.

PubMed

Smith, Rachel A; Sillars, Alan; Chesnut, Ryan P; Zhu, Xun

2018-01-01

Increased genetic testing in personalized medicine presents unique challenges for couples, including managing disease risk and potential discrimination as a couple. This study investigated couples' conflicts and support gaps as they coped with perceived genetic discrimination. We also explored the degree to which communal coping was beneficial in reducing support gaps, and ultimately stress. Dyadic analysis of married adults ( N = 266, 133 couples), in which one person had the genetic risk for serious illness, showed that perceived discrimination predicted more frequent conflicts about AATD-related treatment, privacy boundaries, and finances, which, in turn, predicted wider gaps in emotion and esteem support, and greater stress for both spouses. Communal coping predicted lower support gaps for both partners and marginally lower stress.

The characteristics of rotational slumps and subaqueous translational slab slides of the Lower Murray River, South Australia: do they have any implications for the weak-layer hypothesis?

NASA Astrophysics Data System (ADS)

Hubble, Thomas; De Carli, Elyssa; Airey, David; Breakfree 2012-2013, Scientific Parties MV

2014-05-01

The peak of the recent prolonged 'Millennium Drought' (1997-2011) triggered an episode of widespread mass failure in the alluvial river-banks of the Lower Murray River in South Australia. Multi-beam surveying of the channel and submerged river-banks between Mannum and Murray Bridge and coring of the bank sediments has been undertaken in sections of the river where large bank failures threatened private housing or public infrastructure. This data demonstrates that the bank materials are soft, horizontally-layered muds and that translational, planar slab-slides have frequently occurred in permanently submerged portions of the Murray's river banks. Despite these riverine features being several orders of magnitude smaller than the translational submarine landslides of the continental margins, the submerged river-bank slides are strikingly similar in their morphology to their submarine equivalents. Intriguingly, the Murray River translational slide failure-surfaces are usually developed as river-floor-parallel features in a manner similar to many submarine landslides which present failure-surfaces that are developed on seafloor-parallel, bedding planes. In contrast however, the Murray's river-bank slides occur on steep slopes (>20o) and their failure surfaces must cut across the horizontal laminations and layering of the muds at a relative high angle which removes the possibility of a weak sediment layer being responsible for the occurrence of these failures. Modelling of the river-bank failures with classical soil mechanics methods and the measured physical properties of the river-bank materials indicates that the failures are probably a consequence of flood-flow scour removing the bank-slope toe in combination with pore-pressure effects related to river-level fluctuation (ie. drawdown). Nevertheless, the Murray's translational slab-slides provide a reliable example of slope-parallel planar failure in muds that does not require a stratigraphic weak layer to explain the occurrence of those failures.

Sulu-Celebes-Banda basins: a trapped piece of Cretaceous to Eocene oceanic crust

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

McCabe, R.J.; Hilde, T.W.; Cole, J.T.

1986-07-01

The Sulu-Celebes-Banda basin is composed of three poorly understood marginal basins located between northwest Australia and southeast Asia. Recent studies have proposed that these three basins are remnants of once-continuous ocean basin. The on-land geology of this region is complicated. However, numerous stratigraphic and paleomagnetic studies on pre-Oligocene rocks are consistent with the interpretation that older landmasses presently dissecting the basin were translated into their present position during the middle to late Tertiary. Paleomagnetic data from the Philippines suggest that the Philippine arc is a composite of Early Cretaceous to Holocene arcs that were translated clockwise and from the southeast.more » Paleomagnetic and stratigraphic data from Kalimantan and Sulawesi suggest that these landmasses share a common origin and that Sulawesi was rifted eastward off of Borneo during the late Tertiary. Stratigraphic studies from the Sula microcontinent, Buru, Ceram, and Timor show close correlation to the stratigraphy of northwest Australia or New Guinea. In addition, paleomagnetic studies from Timor suggest that a portion of the island was part of Australia since the early Mesozoic.« less

Multispectral open-air intraoperative fluorescence imaging.

PubMed

Behrooz, Ali; Waterman, Peter; Vasquez, Kristine O; Meganck, Jeff; Peterson, Jeffrey D; Faqir, Ilias; Kempner, Joshua

2017-08-01

Intraoperative fluorescence imaging informs decisions regarding surgical margins by detecting and localizing signals from fluorescent reporters, labeling targets such as malignant tissues. This guidance reduces the likelihood of undetected malignant tissue remaining after resection, eliminating the need for additional treatment or surgery. The primary challenges in performing open-air intraoperative fluorescence imaging come from the weak intensity of the fluorescence signal in the presence of strong surgical and ambient illumination, and the auto-fluorescence of non-target components, such as tissue, especially in the visible spectral window (400-650 nm). In this work, a multispectral open-air fluorescence imaging system is presented for translational image-guided intraoperative applications, which overcomes these challenges. The system is capable of imaging weak fluorescence signals with nanomolar sensitivity in the presence of surgical illumination. This is done using synchronized fluorescence excitation and image acquisition with real-time background subtraction. Additionally, the system uses a liquid crystal tunable filter for acquisition of multispectral images that are used to spectrally unmix target fluorescence from non-target auto-fluorescence. Results are validated by preclinical studies on murine models and translational canine oncology models.

Humboldt slide - A large shear-dominated retrogressive slope failure

USGS Publications Warehouse

Gardner, J.V.; Prior, D.B.; Field, M.E.

1999-01-01

Humboldt Slide is a large, complex slide zone located on the northern California continental margin. Its three-dimensional architecture has been imaged by a combination of multibeam bathymetry, Huntec Deep-Tow seismic profiling, and sidescan sonar. The slide is interpreted to be Late Pleistocene to early Holocene in age and was caused by a combination of factors. The area of the slide is a local depocenter with high accumulation rates of organic-rich sediment; there has been local steepening of slopes by tectonic uplifts; and the entire area is one of high seismicity. Overall, the failure occurred by retrogressive, shear-dominated, minimum movement apparently as a sequence of events. Failure initially occurred by subsidence extension at the middle of the feature, followed by upslope retrogressive failure and downslope compression, and finally by translational sliding at the top of the slide. Degassing, as evidenced by abundant pockmarks, may have inhibited downslope translation. The slide may still be active, as suggested by offsets in Holocene hemipelagic sediment draped over some of the shear surfaces. Crown cracks occur above the present head of the failure and may represent the next generation of failure.

Improved setup and positioning accuracy using a three‐point customized cushion/mask/bite‐block immobilization system for stereotactic reirradiation of head and neck cancer

PubMed Central

Wang, He; Wang, Congjun; Tung, Samuel; Dimmitt, Andrew Wilson; Wong, Pei Fong; Edson, Mark A.; Garden, Adam S.; Rosenthal, David I.; Fuller, Clifton D.; Gunn, Gary B.; Takiar, Vinita; Wang, Xin A.; Luo, Dershan; Yang, James N.; Wong, Jennifer

2016-01-01

The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite‐block (CMB) immobilization system and determine PTV margin for image‐guided head and neck stereotactic ablative radiotherapy (HN‐SABR). We analyzed 105 treatment sessions among 21 patients treated with HN‐SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X‐rays images registered to treatment plans. Residual setup errors were determined using repeat verification X‐ray. The online ExacTrac corrections were compared to cone‐beam CT (CBCT) before treatment to assess agreement. Intrafractional positioning errors were determined using prebeam X‐rays. The systematic and random errors were analyzed. The initial translational setup errors were −0.8±1.3 mm, −0.8±1.6 mm, and 0.3±1.9 mm in AP, CC, and LR directions, respectively, with a three‐dimensional (3D) vector of 2.7±1.4 mm. The initial rotational errors were up to 2.4° if 6D couch is not available. CBCT agreed with ExacTrac X‐ray images to within 2 mm and 2.5°. The intrafractional uncertainties were 0.1±0.6 mm, 0.1±0.6 mm, and 0.2±0.5 mm in AP, CC, and LR directions, respectively, and 0.0∘±0.5°, 0.0∘±0.6°, and −0.1∘±0.4∘ in yaw, roll, and pitch direction, respectively. The translational vector was 0.9±0.6 mm. The calculated PTV margins mPTV(90,95) were within 1.6 mm when using image guidance for online setup correction. The use of image guidance for online setup correction, in combination with our customized CMB device, highly restricted target motion during treatments and provided robust immobilization to ensure minimum dose of 95% to target volume with 2.0 mm PTV margin for HN‐SABR. PACS number(s): 87.55.ne PMID:27167275

Integration of oncologic margins in three-dimensional virtual planning for head and neck surgery, including a validation of the software pathway.

PubMed

Kraeima, Joep; Schepers, Rutger H; van Ooijen, Peter M A; Steenbakkers, Roel J H M; Roodenburg, Jan L N; Witjes, Max J H

2015-10-01

Three-dimensional (3D) virtual planning of reconstructive surgery, after resection, is a frequently used method for improving accuracy and predictability. However, when applied to malignant cases, the planning of the oncologic resection margins is difficult due to visualisation of tumours in the current 3D planning. Embedding tumour delineation on a magnetic resonance image, similar to the routinely performed radiotherapeutic contouring of tumours, is expected to provide better margin planning. A new software pathway was developed for embedding tumour delineation on magnetic resonance imaging (MRI) within the 3D virtual surgical planning. The software pathway was validated by the use of five bovine cadavers implanted with phantom tumour objects. MRI and computed tomography (CT) images were fused and the tumour was delineated using radiation oncology software. This data was converted to the 3D virtual planning software by means of a conversion algorithm. Tumour volumes and localization were determined in both software stages for comparison analysis. The approach was applied to three clinical cases. A conversion algorithm was developed to translate the tumour delineation data to the 3D virtual plan environment. The average difference in volume of the tumours was 1.7%. This study reports a validated software pathway, providing multi-modality image fusion for 3D virtual surgical planning. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Toward Scientific Numerical Modeling

NASA Technical Reports Server (NTRS)

Kleb, Bil

2007-01-01

Ultimately, scientific numerical models need quantified output uncertainties so that modeling can evolve to better match reality. Documenting model input uncertainties and verifying that numerical models are translated into code correctly, however, are necessary first steps toward that goal. Without known input parameter uncertainties, model sensitivities are all one can determine, and without code verification, output uncertainties are simply not reliable. To address these two shortcomings, two proposals are offered: (1) an unobtrusive mechanism to document input parameter uncertainties in situ and (2) an adaptation of the Scientific Method to numerical model development and deployment. Because these two steps require changes in the computational simulation community to bear fruit, they are presented in terms of the Beckhard-Harris-Gleicher change model.

Current understanding of the human microbiome.

PubMed

Gilbert, Jack A; Blaser, Martin J; Caporaso, J Gregory; Jansson, Janet K; Lynch, Susan V; Knight, Rob

2018-04-10

Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities that are associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes and by mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this review, we focus on studies in humans to describe these challenges and propose strategies that leverage existing knowledge to move rapidly from correlation to causation and ultimately to translation into therapies.

Bipolar Nickel-hydrogen Batteries for Aerospace Applications

NASA Technical Reports Server (NTRS)

Koehler, C. W.; Vanommering, G.; Puester, N. H.; Puglisi, V. J.

1984-01-01

A bipolar nickel-hydrogen battery which effectively addresses all key requirements for a spacecraft power system, including long-term reliability and low mass, is discussed. The design of this battery is discussed in the context of system requirements and nickel-hydrogen battery technology in general. To achieve the ultimate goal of an aerospace application of a bipolar Ni-H2 battery several objectives must be met in the design and development of the system. These objectives include: maximization of reliability and life; high specific energy and energy density; reasonable cost of manufacture, test, and integration; and ease in scaling for growth in power requirements. These basic objectives translate into a number of specific design requirements, which are discussed.

"On the other hand ...": the evidence does not support the use of hand-carried ultrasound by hospitalists.

PubMed

Feldman, Mitchell D; Petersen, Amy Jean; Tice, Jeffrey A

2010-03-01

In the right hands, ultrasound is a safe and helpful diagnostic imaging tool. However, evidence supporting the use of hand-carried ultrasound (HCU) by hospitalist physicians has not kept pace with expanding application of these devices. In spite of its strategic point-of-care benefit, use of this technology by hospitalists may not ultimately translate into improved efficiency and better clinical outcomes. Optimal levels of training in image acquisition and interpretation remain to be established. Novelty, availability, and the results of a few small studies lacking patient-centered outcomes remain insufficient grounds to justify the expanded clinical utilization of these medical imaging devices by nonspecialists.

Current understanding of the human microbiome

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

Gilbert, Jack A.; Blaser, Martin J.; Caporaso, J. Gregory

Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledgemore » to move rapidly from correlation to causation, and ultimately to translation.« less

Voice of the customer---a roadmap for service improvement.

PubMed

Uberoi, Ravinder S; Nayak, Yogamaya; Sachdeva, Pritindira; Sibal, Anupam

2013-01-01

Patient satisfaction surveys help a great deal in identifying ways of improving a hospital's services. Ultimately, that translates into better care and happier patients. Moreover, it shows the staff and the community that the hospital is serious about quality and is looking for ways to improve. This article describes how the Voice of the Customer (VOC) Survey can be used as a tool for improving services. Regular monitoring of VOC scores is essential for minimizing the gaps between service delivery and patient expectations. The present study showcases the various initiatives undertaken to improve the VOC scores from an original 4.40 to 4.77 (on a 5 point scale) at the hospital under study.

How criminal system racial disparities may translate into health disparities.

PubMed

Iguchi, Martin Y; Bell, James; Ramchand, Rajeev N; Fain, Terry

2005-11-01

Disadvantaged racial and ethnic minorities in the U.S. are strikingly over-represented in the juvenile justice and adult criminal justice systems. This paper briefly reviews the extent of over-representation attributable primarily to drug offenses and an earlier conceptual framework introduced by Iguchi and colleagues showing how the use of incarceration as a key drug control tool has disproportionately affected the health and well being of racial and ethnic minority communities. We then provide observations from the field that demonstrate how the implementation of a quality assessment approach might be used to mitigate procedural/structural biases that contribute to disparities in minority confinement, and ultimately, to reduce disparities in access to resources and health care.

A Strategic Planning Tool for Increasing African American Blood Donation.

PubMed

Singleton, Ashley; Spratling, Regena

2018-05-01

Historically, African Americans (AAs) have been underrepresented as blood donors. Having a lack of racially diverse blood donors contributes to transfusion complications, particularly in patients with sickle cell disease, who are both disproportionately AA and the recipients of frequent transfusions. Increasing AA blood donation is a complex public health issue. This review article serves to fill a gap in translating research regarding known hindrances and facilitators of AA blood donation to improve real-world donation practice and ultimately, patient outcomes. We incorporate findings from a literature review to develop a tool that blood centers, provider organizations, and patient advocacy groups can use to aid strategic planning efforts aimed at increasing AA blood donation.

Cognitive Competence as a Positive Youth Development Construct: A Conceptual Review

PubMed Central

Sun, Rachel C. F.; Hui, Eadaoin K. P.

2012-01-01

This paper focuses on discussing critical thinking and creative thinking as the core cognitive competence. It reviews and compares several theories of thinking, highlights the features of critical thinking and creative thinking, and delineates their interrelationships. It discusses cognitive competence as a positive youth development construct by linking its relationships with adolescent development and its contributions to adolescents' learning and wellbeing. Critical thinking and creative thinking are translated into self-regulated cognitive skills for adolescents to master and capitalize on, so as to facilitate knowledge construction, task completion, problem solving, and decision making. Ways of fostering these thinking skills, cognitive competence, and ultimately positive youth development are discussed. PMID:22654575

A hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Lei, Yu; Wu, Qiuwen

2010-04-21

Offline adaptive radiotherapy (ART) has been used to effectively correct and compensate for prostate motion and reduce the required margin. The efficacy depends on the characteristics of the patient setup error and interfraction motion through the whole treatment; specifically, systematic errors are corrected and random errors are compensated for through the margins. In online image-guided radiation therapy (IGRT) of prostate cancer, the translational setup error and inter-fractional prostate motion are corrected through pre-treatment imaging and couch correction at each fraction. However, the rotation and deformation of the target are not corrected and only accounted for with margins in treatment planning. The purpose of this study was to investigate whether the offline ART strategy is necessary for an online IGRT protocol and to evaluate the benefit of the hybrid strategy. First, to investigate the rationale of the hybrid strategy, 592 cone-beam-computed tomography (CBCT) images taken before and after each fraction for an online IGRT protocol from 16 patients were analyzed. Specifically, the characteristics of prostate rotation were analyzed. It was found that there exist systematic inter-fractional prostate rotations, and they are patient specific. These rotations, if not corrected, are persistent through the treatment fraction, and rotations detected in early fractions are representative of those in later fractions. These findings suggest that the offline adaptive replanning strategy is beneficial to the online IGRT protocol with further margin reductions. Second, to quantitatively evaluate the benefit of the hybrid strategy, 412 repeated helical CT scans from 25 patients during the course of treatment were included in the replanning study. Both low-risk patients (LRP, clinical target volume, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles) were included in the simulation. The contours of prostate and seminal vesicles were delineated on each CT. The benefit of margin reduction to compensate for both rotation and deformation in the hybrid strategy was evaluated geometrically. With the hybrid strategy, the planning margins can be reduced by 1.4 mm for LRP, and 2.0 mm for IRP, compared with the standard online IGRT only, to maintain the same 99% target volume coverage. The average relative reduction in planning target volume (PTV) based on the internal target volume (ITV) from PTV based on CTV is 19% for LRP, and 27% for IRP.

Origin, transport, and emplacement of an exotic island-arc terrane exposed in eastern Kamchatka, Russia

USGS Publications Warehouse

Geist, Eric L.; Vallier, Tracy L.; Scholl, David W.

1994-01-01

The regional stratigraphy of eastern Kamchatka includes an exotic, Early-Late Cretaceous ophiolite and Late Cretaceous island-arc volcanic sequence. Integrating the existing geologic and geophysical data, we examine the origin, transport, emplacement, and postemplacement deformation of the island-arc terrane, which is named the Olyutorsky island arc. Results from several paleomagnetic studies consistently indicate that the island-arc terrane originated >1000 km to the south of where it is presently exposed. Although the formative paleolatitudes of the island-arc rocks approximately correspond to the location of the Izanagi-Farallon subduction zone, the age of the volcanic rocks postdates the cessation of Izanagi-Farallon convergence, thus indicating that an unnamed plate or back-arc basin existed in the northwest Pacific during Late Cretaceous time. We examine two possible models for northward transport of the island-arc terrane to Kamchatka: (1) infra-oceanic transport with the Pacific or Kula plates and (2) coastwise translation of the island-arc terrane after accretion to the Eurasian margin far to the south of Kamchatka. For both models, the dominant Eocene and Miocene deformation ages observed in eastern Kamchatka are used as two possible age limits for the cessation of northward transport. Although the observed paleolatitudes from paleomagnetic data correspond best with the infra-oceanic transport model, the provenance of the Paleogene "transport" stratigraphy indicates a near-shore sediment supply. Our preferred interpretation is that the island-arc terrane (1) accreted onto the Eurasian margin concurrent with cessation of island-arc volcanism (Maastrichtian-Danian) and (2) underwent northward coastwise translation along a major strike-slip fault zone ending by middle-late Eocene time (43-50 Ma). It is unclear whether the ophiolite was exposed during arc-continent collision or whether the ophiolite was obducted onto the island arc prior to collision. A consequence of either infra-oceanic transport or coastwise translation is that an open corridor between the western terminus of the Aleutian Arc and Kamchatka must have existed until middle to late Eocene time. Spreading within the Komandorsky Basin, subduction of sea-mounts, and collision of the Aleutian Arc with Kamchatka are proposed to have instigated the second Miocene phase of deformation, which uplifted and reexposed the island-arc terrane.

Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering.

PubMed

Holzapfel, Boris Michael; Wagner, Ferdinand; Thibaudeau, Laure; Levesque, Jean-Pierre; Hutmacher, Dietmar Werner

2015-06-01

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to "make the model organism mouse more human." To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems. © 2015 AlphaMed Press.

Application of the Intervention Mapping Framework to Develop an Integrated Twenty-first Century Core Curriculum-Part Two: Translation of MPH Core Competencies into an Integrated Theory-Based Core Curriculum.

PubMed

Corvin, Jaime A; DeBate, Rita; Wolfe-Quintero, Kate; Petersen, Donna J

2017-01-01

In the twenty-first century, the dynamics of health and health care are changing, necessitating a commitment to revising traditional public health curricula to better meet present day challenges. This article describes how the College of Public Health at the University of South Florida utilized the Intervention Mapping framework to translate revised core competencies into an integrated, theory-driven core curriculum to meet the training needs of the twenty-first century public health scholar and practitioner. This process resulted in the development of four sequenced courses: History and Systems of Public Health and Population Assessment I delivered in the first semester and Population Assessment II and Translation to Practice delivered in the second semester. While the transformation process, moving from traditional public health core content to an integrated and innovative curriculum, is a challenging and daunting task, Intervention Mapping provides the ideal framework for guiding this process. Intervention mapping walks the curriculum developers from the broad goals and objectives to the finite details of a lesson plan. Throughout this process, critical lessons were learned, including the importance of being open to new ideologies and frameworks and the critical need to involve key-stakeholders in every step of the decision-making process to ensure the sustainability of the resulting integrated and theory-based curriculum. Ultimately, as a stronger curriculum emerged, the developers and instructors themselves were changed, fostering a stronger public health workforce from within.

Amyloid Precursor Protein and Alpha Synuclein Translation, Implications for Iron and Inflammation in Neurodegenerative diseases

PubMed Central

Cahill, Catherine M.; Lahiri, Debomoy K.; Huang, Xudong; Rogers, Jack T.

2014-01-01

Summary Recent studies that alleles in the hemochromatosis gene may accelerate the onset of Alzheimer's disease (AD) by five years have validated interest in the model in which metals (particularly iron) accelerate disease course. Biochemical and biophysical measurements demonstrated the presence of elevated levels of neurotoxic copper, zinc and iron in the brains of AD patients. Intracellular levels of amyloid precursor protein (APP) holoprotein were shown to be modulated via iron by a mechanism that is similar to the translation control of the ferritin L- and H mRNAs by Iron-responsive Element (IRE) RNA stem loops in their 5′untranslated regions (5′UTRs). Recently, we reported a putative IRE-like sequence to be present in the 5′UTR of the Parkinson's disease (PD) specific alpha synuclein (ASYN) transcript. ASYN encodes the non-Aβ component (NAC) of amyloid plaques. The demonstration of iron-dependent translation of APP mRNA, the involvement of metals in the plaque of AD patients and of increased iron in striatal neurons in the Substantia nigra (SN) of PD patients, have each encouraged the development of metal attenuating agents and iron chelators as a major new therapeutic strategy for the treatment of these neurodegenerative diseases. In the case of AD, metal based therapeutics may ultimately prove more cost effective than the use of an amyloid vaccine as the preferred anti-amyloid therapeutic strategy to ameliorate the cognitive decline of AD patients. PMID:19166904

Geophysical reassessment of the role of ancient crustal structures on the development of western Laurentia and Selwyn Basin, Yukon and Northwest Territories, Canada.

NASA Astrophysics Data System (ADS)

Hayward, N.

2017-12-01

The structure of the western margin of the North American craton (Laurentia) in the northern Canadian Cordillera and its role in the development of the Neoproterozoic-Early Paleozoic Selwyn Basin are reassessed through 3D inversion of a new compilation of aeromagnetic data and archival Bouguer gravity data. The region's tectonic history is obscured by partial burial beneath Selwyn Basin, and a tectonic overprint that includes terrane accretion, regional plutonism, and strike-slip faults with displacements of 100s and perhaps 1000s of kilometers. Despite the implied complexity, preliminary geological and geophysical based interpretations of the structure of the western margin of Laurentia, have been adopted with few refinements in over two decades. Regionally continuous, NE-trending, crustal lineaments, including the Fort Norman line and Leith Ridge fault, were interpreted as having had long-standing influence on the craton development, its western margin, and overlapping sedimentary basin. New results reveal limited evidence for the regional continuity of the NE-trending lineaments. Instead, models suggest that the structure of the Laurentian margin is characterised by segmentation on numerous shorter structures of varied strike. The western margin of the craton and its structures are bound by a NW-trending structure that connects with the Richardson Trough to the north and may have been active during rifting of the Misty Creek embayment. This boundary also marks the easternmost limit of both granitic intrusions in Selwyn Basin, which gravity models suggest are of greater extent than reflected on geological maps, and SEDEX occurrences. An ENE-trending structure beneath northern Selwyn Basin is interpreted as marking the southern edge of a previously unidentified cratonic promontory, akin to the Liard line that marks a transfer fault that bounds the promontory of the Macdonald Platform, south of Selwyn Basin. The ENE-trending structure is traced from the Tintina fault in the west to near to the Great Bear magmatic zone. The structure's regional continuity also limits the interpretation of a post-Cretaceous structure, inboard of the Tintina fault that could be responsible for 1000's km of dextral strike-slip ascribed to the Baja-BC terrane translation model.

Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues.

PubMed

Molenaar, Remco J; Khurshed, Mohammed; Hira, Vashendriya V V; Van Noorden, Cornelis J F

2018-05-26

Altered cellular metabolism is a hallmark of many diseases, including cancer, cardiovascular diseases and infection. The metabolic motor units of cells are enzymes and their activity is heavily regulated at many levels, including the transcriptional, mRNA stability, translational, post-translational and functional level. This complex regulation means that conventional quantitative or imaging assays, such as quantitative mRNA experiments, Western Blots and immunohistochemistry, yield incomplete information regarding the ultimate activity of enzymes, their function and/or their subcellular localization. Quantitative enzyme cytochemistry and histochemistry (i.e., metabolic mapping) show in-depth information on in situ enzymatic activity and its kinetics, function and subcellular localization in an almost true-to-nature situation. We describe a protocol to detect the activity of dehydrogenases, which are enzymes that perform redox reactions to reduce cofactors such as NAD(P) + and FAD. Cells and tissue sections are incubated in a medium that is specific for the enzymatic activity of one dehydrogenase. Subsequently, the dehydrogenase that is the subject of investigation performs its enzymatic activity in its subcellular site. In a chemical reaction with the reaction medium, this ultimately generates blue-colored formazan at the site of the dehydrogenase's activity. The formazan's absorbance is therefore a direct measure of the dehydrogenase's activity and can be quantified using monochromatic light microscopy and image analysis. The quantitative aspect of this protocol enables researchers to draw statistical conclusions from these assays. Besides observational studies, this technique can be used for inhibition studies of specific enzymes. In this context, studies benefit from the true-to-nature advantages of metabolic mapping, giving in situ results that may be physiologically more relevant than in vitro enzyme inhibition studies. In all, metabolic mapping is an indispensable technique to study metabolism at the cellular or tissue level. The technique is easy to adopt, provides in-depth, comprehensive and integrated metabolic information and enables rapid quantitative analysis.

The financial performance of labor and delivery units.

PubMed

von Gruenigen, Vivian E; Powell, Diane M; Sorboro, Susan; McCarroll, Michelle L; Kim, Unhee

2013-07-01

Hospitals and health care systems are already seeing the effect of health care reform with declining dollars. Hospital services, which had narrow financial margins in the past, will have further challenges. This article will review definitions, challenges, and potential financial solutions for labor and delivery units. Improving quality, efficiency, and cost requires substantial physician cooperation in the changing paradigm from physician-centric care to the transparent safety of teams. The financial contribution margin should increase the net revenue, but significant volumes are also needed. The challenge of this model for obstetrics is the slowing birth rate with the ultimate limitation for growth. Therefore, cost containment is imperative for sustainability. Standardization of hospital policies and procedures can improve quality and cost-savings with new incentive models. Examples include decreasing expensive pharmaceuticals, minimizing elective inductions of labor, and encouraging breast-feeding. As providers of health care to women, we all must engage in the triple aim of (1) improving the experience of care, (2) improving the health of populations, and (3) reducing per capita costs of health care. Although accountable care organizations presently are focused on Medicare populations for cost containment, all health care providers and institutions must be vigilant on both quality cost-effective care for sustainability, especially in obstetrics. Copyright © 2013 Mosby, Inc. All rights reserved.

Predicting Health Care Utilization in Marginalized Populations: Black, Female, Street-based Sex Workers

PubMed Central

Varga, Leah M.; Surratt, Hilary L.

2014-01-01

Background Patterns of social and structural factors experienced by vulnerable populations may negatively affect willingness and ability to seek out health care services, and ultimately, their health. Methods The outcome variable was utilization of health care services in the previous 12 months. Using Andersen’s Behavioral Model for Vulnerable Populations, we examined self-reported data on utilization of health care services among a sample of 546 Black, street-based female sex workers in Miami, Florida. To evaluate the impact of each domain of the model on predicting health care utilization, domains were included in the logistic regression analysis by blocks using the traditional variables first and then adding the vulnerable domain variables. Findings The most consistent variables predicting health care utilization were having a regular source of care and self-rated health. The model that included only enabling variables was the most efficient model in predicting health care utilization. Conclusions Any type of resource, link, or connection to or with an institution, or any consistent point of care contributes significantly to health care utilization behaviors. A consistent and reliable source for health care may increase health care utilization and subsequently decrease health disparities among vulnerable and marginalized populations, as well as contribute to public health efforts that encourage preventive health. PMID:24657047

Gunbarrel mafic magmatic event: A key 780 Ma time marker for Rodinia plate reconstructions

USGS Publications Warehouse

Harlan, S.S.; Heaman, L.; LeCheminant, A.N.; Premo, W.R.

2003-01-01

Precise U-Pb baddeleyite dating of mafic igneous rocks provides evidence for a widespread and synchronous magmatic event that extended for >2400 km along the western margin of the Neoproterozoic Laurentian craton. U-Pb baddeleyite analyses for eight intrusions from seven localities ranging from the northern Canadian Shield to northwestern Wyoming-southwestern Montana are statistically indistinguishable and yield a composite U-Pb concordia age for this event of 780.3 ?? 1.4 Ma (95% confidence level). This 780 Ma event is herein termed the Gunbarrel magmatic event. The mafic magmatism of the Gunbarrel event represents the largest mafic dike swarm yet identified along the Neoproterozoic margin of Laurentia. The origin of the mafic magmatism is not clear, but may be related to mantle-plume activity or upwelling asthenosphere leading to crustal extension accompanying initial breakup of the supercontinent Rodinia and development of the proto-Pacific Ocean. The mafic magmatism of the Gunbarrel magmatic event at 780 Ma predates the voluminous magmatism of the 723 Ma Franklin igneous event of the northwestern Canadian Shield by ???60 m.y. The precise dating of the extensive Neoproterozoic Gunbarrel and Franklin magmatic events provides unique time markers that can ultimately be used for robust testing of Neoproterozoic continental reconstructions.

Leonardo Da Vinci, the genius and the monsters. Casual encounters?

PubMed

Ciseri, Lorenzo Montemagno

2014-01-01

This article analyses Leonardo's interest in monsters and deformed reality, one of the lesser known aspects of his vast and multifaceted output. With the possible exception of his studies of physiognomy, relevant drawings, sketches and short stories represent a marginal aspect of his work, but they are nevertheless significant for historians of teratology. The purpose of this study is to provide a broad overview of the relationship between Leonardo and both the literature on mythological monsters and the reports on monstrous births that he either read about or witnessed personally. While aspects of his appreciation and attention to beauty and the pursuit of perfection and good proportions are the elements most emphasised in Leonardo's work, other no less interesting aspects related to deformity have been considered of marginal importance. My analysis will demonstrate that Leonardo approached the realm of monstrosity as if he considered abnormality a mirror of normality, deformity a mirror of harmony, and disease a mirror of health, as if to emphasise that, ultimately, it is the monster that gives the world the gift of normality. Two special cases of monstrosity are analysed: the famous monster of Ravenna, whose image was found among his papers, and a very rare case of parasitic conjoined twins (thoracopagus parasiticus) portrayed for the first time alive, probably in Florence, by Leonardo himself.

Outcomes of multiple wire localization for larger breast cancers: when can mastectomy be avoided?

PubMed

Kirstein, Laurie J; Rafferty, Elizabeth; Specht, Michelle C; Moore, Richard H; Taghian, Alphonse G; Hughes, Kevin S; Gadd, Michele A; Smith, Barbara L

2008-09-01

Mastectomy is often recommended when mammography shows a breast cancer with extensive calcifications. We wished to determine whether the use of multiple localizing wires to guide lumpectomy in this setting was associated with increased rates of breast conservation. We also wanted to identify factors that predicted a poor chance of successful lumpectomy, to avoid multiple lumpectomy attempts in a patient who would ultimately require mastectomy. Records of 153 women with breast cancer who underwent lumpectomy for larger lesions that required multiple wire localization and 196 controls who required only single wire localization were reviewed retrospectively. The number of localizing wires, specimen volume, largest specimen dimension, number of surgical procedures, and rates of breast conservation were scored. Seventy-seven percent of patients requiring multiple wire localization had successful breast conservation, compared with 90% of those needing only single wire localization. Only 28% of multiple wire patients required more than 1 excision to achieve clear margins, compared with 36% of single wire patients (p < 0.01). Breast conservation is possible in the great majority of breast cancer patients whose mammographic lesions require multiple localizing wires for excision. The use of multiple wires can decrease the number of procedures required to obtain clear lumpectomy margins.

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

Smith, Curtis L.; Prescott, Steven; Coleman, Justin

This report describes the current progress and status related to the Industry Application #2 focusing on External Hazards. For this industry application within the Light Water Reactor Sustainability (LWRS) Program Risk-Informed Safety Margin Characterization (RISMC) R&D Pathway, we will create the Risk-Informed Margin Management (RIMM) approach to represent meaningful (i.e., realistic facility representation) event scenarios and consequences by using an advanced 3D facility representation that will evaluate external hazards such as flooding and earthquakes in order to identify, model and analyze the appropriate physics that needs to be included to determine plant vulnerabilities related to external events; manage the communicationmore » and interactions between different physics modeling and analysis technologies; and develop the computational infrastructure through tools related to plant representation, scenario depiction, and physics prediction. One of the unique aspects of the RISMC approach is how it couples probabilistic approaches (the scenario) with mechanistic phenomena representation (the physics) through simulation. This simulation-based modeling allows decision makers to focus on a variety of safety, performance, or economic metrics. In this report, we describe the evaluation of various physics toolkits related to flooding representation. Ultimately, we will be coupling the flooding representation with other events such as earthquakes in order to provide coupled physics analysis for scenarios where interactions exist.« less

Designing a post-genomics knowledge ecosystem to translate pharmacogenomics into public health action.

PubMed

Dove, Edward S; Faraj, Samer A; Kolker, Eugene; Ozdemir, Vural

2012-01-01

Translation of pharmacogenomics to public health action is at the epicenter of the life sciences agenda. Post-genomics knowledge is simultaneously co-produced at multiple scales and locales by scientists, crowd-sourcing and biological citizens. The latter are entrepreneurial citizens who are autonomous, self-governing and increasingly conceptualizing themselves in biological terms, ostensibly taking responsibility for their own health, and engaging in patient advocacy and health activism. By studying these heterogeneous 'scientific cultures', we can locate innovative parameters of collective action to move pharmacogenomics to practice (personalized therapeutics). To this end, we reconceptualize knowledge-based innovation as a complex ecosystem comprising 'actors' and 'narrators'. For robust knowledge translation, we require a nested post-genomics technology governance system composed of first-order narrators (for example, social scientists, philosophers, bioethicists) situated at arm's length from innovation actors (for example, pharmacogenomics scientists). Yet, second-order narrators (for example, an independent and possibly crowd-funded think-tank of citizen scholars, marginalized groups and knowledge end-users) are crucial to prevent first-order narrators from gaining excessive power that can be misused in the course of steering innovations. To operate such 'self-calibrating' and nested innovation ecosystems, we introduce the concept of 'wiki-governance' to enable mutual and iterative learning among innovation actors and first- and second-order narrators. '[A] scientific expert is someone who knows more and more about less and less, until finally knowing (almost) everything about (almost) nothing.' [1] 'Ubuntu: I am because you are.' [2].

Designing a post-genomics knowledge ecosystem to translate pharmacogenomics into public health action

PubMed Central

2012-01-01

Translation of pharmacogenomics to public health action is at the epicenter of the life sciences agenda. Post-genomics knowledge is simultaneously co-produced at multiple scales and locales by scientists, crowd-sourcing and biological citizens. The latter are entrepreneurial citizens who are autonomous, self-governing and increasingly conceptualizing themselves in biological terms, ostensibly taking responsibility for their own health, and engaging in patient advocacy and health activism. By studying these heterogeneous 'scientific cultures', we can locate innovative parameters of collective action to move pharmacogenomics to practice (personalized therapeutics). To this end, we reconceptualize knowledge-based innovation as a complex ecosystem comprising 'actors' and 'narrators'. For robust knowledge translation, we require a nested post-genomics technology governance system composed of first-order narrators (for example, social scientists, philosophers, bioethicists) situated at arm's length from innovation actors (for example, pharmacogenomics scientists). Yet, second-order narrators (for example, an independent and possibly crowd-funded think-tank of citizen scholars, marginalized groups and knowledge end-users) are crucial to prevent first-order narrators from gaining excessive power that can be misused in the course of steering innovations. To operate such 'self-calibrating' and nested innovation ecosystems, we introduce the concept of 'wiki-governance' to enable mutual and iterative learning among innovation actors and first- and second-order narrators. '[A] scientific expert is someone who knows more and more about less and less, until finally knowing (almost) everything about (almost) nothing.' [1] 'Ubuntu: I am because you are.' [2] PMID:23194449

Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

PubMed

Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

2011-03-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

Host-dependent variables: The missing link to personalized medicine.

PubMed

Demlova, Regina; Zdrazilova-Dubska, Lenka; Sterba, Jaroslav; Stanta, Giorgio; Valik, Dalibor

2018-04-26

Individualized medicine has the potential to tailor anticancer therapy with the best response and highest safety margin to provide better patient care. However, modern targeted therapies are still being tested through clinical trials comparing preselected patient cohorts and assessed upon behaviour of group averages. Clinically manifesting malignant disease requires identification of host- and tumour-dependent variables such as biological characteristics of the tumour and its microenvironment including immune response features, and overall capacity of the host to receive, tolerate and efficiently utilize treatment. Contemporary medical oncology including clinical trial design need to refocus from assessing group averages to individuality taking into consideration time dependent host-associated characteristics and reinventing outliers to be appreciated as naturally occurring variables collectively determining the ultimate outcome of malignant disease. Copyright © 2018. Published by Elsevier Ltd.

Assessment of three-dimensional setup errors in image-guided pelvic radiotherapy for uterine and cervical cancer using kilovoltage cone-beam computed tomography and its effect on planning target volume margins.

PubMed

Patni, Nidhi; Burela, Nagarjuna; Pasricha, Rajesh; Goyal, Jaishree; Soni, Tej Prakash; Kumar, T Senthil; Natarajan, T

2017-01-01

To achieve the best possible therapeutic ratio using high-precision techniques (image-guided radiation therapy/volumetric modulated arc therapy [IGRT/VMAT]) of external beam radiation therapy in cases of carcinoma cervix using kilovoltage cone-beam computed tomography (kV-CBCT). One hundred and five patients of gynecological malignancies who were treated with IGRT (IGRT/VMAT) were included in the study. CBCT was done once a week for intensity-modulated radiation therapy and daily in IGRT/VMAT. These images were registered with the planning CT scan images and translational errors were applied and recorded. In all, 2078 CBCT images were studied. The margins of planning target volume were calculated from the variations in the setup. The setup variation was 5.8, 10.3, and 5.6 mm in anteroposterior, superoinferior, and mediolateral direction. This allowed adequate dose delivery to the clinical target volume and the sparing of organ at risks. Daily kV-CBCT is a satisfactory method of accurate patient positioning in treating gynecological cancers with high-precision techniques. This resulted in avoiding geographic miss.

Detrital zircons from the Nanaimo basin, Vancouver Island, British Columbia: An independent test of Late Cretaceous to Cenozoic northward translation

NASA Astrophysics Data System (ADS)

Matthews, W. A.; Guest, B.; Coutts, D.; Bain, H.; Hubbard, S.

2017-05-01

The development of the Cordilleran orogen of western North American is disputed despite a century of study. Paleomagnetic observations require large-scale dextral displacements of crustal fragments along the western margin of North America, from low latitudes to moderate latitudes during the Cretaceous-Paleogene. A lack of corroborating geological evidence for large-scale (>1500 km) displacements has prevented the widespread integration of paleomagnetic data into most contemporary tectonic models for the margin. Here we use detrital zircons from the Nanaimo basin, southwestern British Columbia, Canada as an independent test of its Late Cretaceous paleogeographic position. We compare 4310 detrital zircon U/Pb dates from 16 samples to potential source areas in western North America to test hypothesized northern and southern Late Cretaceous paleogeographic positions. Our detrital zircon data suggest that sediment in the Nanaimo basin derives from either a geographically restricted portion of the Belt-Purcell basin or the Mojave-Sonoran region of southwestern North America. A paleogeographic position for the basin adjacent to the Mojave-Sonoran region is preferred as it is consistent with the paleomagnetic results, but further geological, isotopic, or geophysical data are required to rule out a Belt-Purcell source.

Using translational medicine to understand clinical differences between botulinum toxin formulations.

PubMed

Aoki, K R; Ranoux, D; Wissel, J

2006-12-01

When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.

The material, moral, and affective worlds of dealing and crime among young men entrenched in an inner city drug scene.

PubMed

Fast, Danya; Shoveller, Jean; Kerr, Thomas

2017-06-01

A large body of previous research has elucidated how involvement in drug dealing and crime among marginalized urban youth who use drugs is shaped by the imperatives of addiction and survival in the context of poverty. However, a growing body of research has examined how youth's involvement in these activities is shaped by more expansive desires and moralities. In this paper, we examine the material, moral, and affective worlds of loosely gang affiliated, street level dealing and crime among one group of young men in Vancouver, Canada. Drawing on longitudinal interviews with 44 young men from 2008 to 2016, and ethnographic fieldwork with a group of approximately 15 of those young men over the same time period, we argue that for these youth, dealing and crime were not solely about economic survival, or even the accrual of highly meaningful forms of "street capital" in the margins. Rather, as "regimes of living," dealing and crime also opened up new value systems, moral logics, and affects in relation to the tremendous risks, potential rewards, and crushing boredom of life in the margins. These activities were also understood as a way into deeply desired forms of social spatial belonging in the city, which had previously only been imagined. However, across time dealing and crime "embedded" young men in cycles of incarceration, destitution, addictions, and mental health crises that ultimately reinforced their exclusion-from legal employment, but also within the world of crime. The findings of this study underscore the importance of adopting a life course perspective in order to meaningfully address the harms associated with involvement in dealing and crime among youth in our setting. Copyright © 2017 Elsevier B.V. All rights reserved.

Surgical strategy for bile duct cancer: Advances and current limitations

PubMed Central

Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Hashimoto, Daijo

2011-01-01

The aim of this review is to describe recent advances and topics in the surgical management of bile duct cancer. Radical resection with a microscopically negative margin (R0) is the only way to cure cholangiocarcinoma and is associated with marked survival advantages compared to margin-positive resections. Complete resection of the tumor is the surgeon’s ultimate aim, and several advances in the surgical treatment for bile duct cancer have been made within the last two decades. Multidetector row computed tomography has emerged as an indispensable diagnostic modality for the precise preoperative evaluation of bile duct cancer, in terms of both longitudinal and vertical tumor invasion. Many meticulous operative procedures have been established, especially extended hepatectomy for hilar cholangiocarcinoma, to achieve a negative resection margin, which is the only prognostic factor under the control of the surgeon. A complete caudate lobectomy and resection of the inferior part of Couinaud’s segment IV coupled with right or left hemihepatectomy has become the standard surgical procedure for hilar cholangiocarcinoma, and pylorus-preserving pancreaticoduodenectomy is the first choice for distal bile duct cancer. Limited resection for middle bile duct cancer is indicated for only strictly selected cases. Preoperative treatments including biliary drainage and portal vein embolization are also indicated for only selected patients, especially jaundiced patients anticipating major hepatectomy. Liver transplantation seems ideal for complete resection of bile duct cancer, but the high recurrence rate and decreased patient survival after liver transplant preclude it from being considered standard treatment. Adjuvant chemotherapy and radiotherapy have a potentially crucial role in prolonging survival and controlling local recurrence, but no definite regimen has been established to date. Further evidence is needed to fully define the role of liver transplantation and adjuvant chemo-radiotherapy. PMID:21603318

Paleozoic tectonics of the Ouachita Orogen through Nd isotopes

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

Gleason, J.D.; Patchett, P.J.; Dickinson, W.R.

1992-01-01

A combined isotopic and trace-element study of the Late Paleozoic Ouachita Orogenic belt has the following goals: (1) define changing provenance of Ouachita sedimentary systems throughout the Paleozoic; (2) constrain sources feeding into the Ouachita flysch trough during the Late Paleozoic; (3) isolate the geochemical signature of proposed colliding terranes to the south; (4) build a data base to compare with possible Ouachita System equivalents in Mexico. The ultimate aim is to constrain the tectonic setting of the southern margin of North America during the Paleozoic, with particular emphasis on collisional events leading to the final suturing of Pangea. Ndmore » isotopic data identify 3 distinct groups: (1) Ordovician passive margin sequence; (2) Carboniferous proto-flysch (Stanley Fm.), main flysch (Jackfork and Atoka Fms.) and molasse (foreland Atoka Fm.); (3) Mississippian ash-flow tuffs. The authors interpret the Ordovician signature to be essentially all craton-derived, whereas the Carboniferous signature reflects mixed sources from the craton plus orogenic sources to the east and possibly the south, including the evolving Appalachian Orogen. The proposed southern source is revealed by the tuffs to be too old and evolved to be a juvenile island arc terrane. They interpret the tuffs to have been erupted in a continental margin arc-type setting. Surprisingly, the foreland molasse sequence is indistinguishable from the main trough flysch sequence, suggesting the Ouachita trough and the craton were both inundated with sediment of a single homogenized isotopic signature during the Late Carboniferous. The possibility that Carboniferous-type sedimentary dispersal patterns began as early as the Silurian has important implications for the tectonics and paleogeography of the evolving Appalachian-Ouachita Orogenic System.« less

Strategies and Challenges in Clinical Trials Targeting Human Aging

PubMed Central

Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

2016-01-01

Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

Murine models of breast cancer bone metastasis

PubMed Central

Wright, Laura E; Ottewell, Penelope D; Rucci, Nadia; Peyruchaud, Olivier; Pagnotti, Gabriel M; Chiechi, Antonella; Buijs, Jeroen T; Sterling, Julie A

2016-01-01

Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats. In this methods review, we characterize the bone phenotype of commonly utilized human- and murine-derived breast cell lines that elicit osteoblastic and/or osteolytic destruction of bone in mice and report methods for optimizing tumor-take in murine models of bone metastasis. We then provide protocols for four of the most common xenograft and syngeneic inoculation routes for modeling breast cancer metastasis to the skeleton in mice, including the intra-cardiac, intra-arterial, orthotopic and intra-tibial methods of tumor cell injection. Recommendations for in vivo and ex vivo assessment of tumor progression and bone destruction are provided, followed by discussion of the strengths and limitations of the available tools and translational models that aid investigators in the study of breast cancer metastasis to bone. PMID:27867497

Self-regulation and performance level of elite and non-elite youth soccer players.

PubMed

Toering, T T; Elferink-Gemser, M T; Jordet, G; Visscher, C

2009-12-01

In learning and development, self-regulation can be described as the extent to which individuals are metacognitively, motivationally, and behaviourally proactive participants in their learning process (Zimmerman, 1989, 2006). We examined the relationship between self-regulation and performance level in elite (n = 159) and non-elite (n = 285) youth soccer players aged 11-17 years (mean 14.5 years, s = 1.4). The players completed a questionnaire that assessed planning, self-monitoring, evaluation, reflection, effort, and self-efficacy. A logistic regression analysis was performed (controlling for age) to determine which self-regulatory aspects were associated with players' performance level (elite vs. non-elite). High scores on reflection and effort were associated with a higher level of performance. Findings suggest that elite players may be more aware of their strong and weak points as well as better able to translate this awareness into action. In addition, elite players appear to be more willing to invest effort into practice and competition. It is suggested that these better developed self-regulatory skills may translate into a more effective learning environment and ultimately result in an increased capacity for performance in elite players relative to their non-elite peers.

Accelerators: Sparking Innovation and Transdisciplinary Team Science in Disparities Research

PubMed Central

Horowitz, Carol R.; Shameer, Khader; Gabrilove, Janice; Atreja, Ashish; Shepard, Peggy; Goytia, Crispin N.; Smith, Geoffrey W.; Dudley, Joel; Manning, Rachel; Bickell, Nina A.; Galvez, Maida P.

2017-01-01

Development and implementation of effective, sustainable, and scalable interventions that advance equity could be propelled by innovative and inclusive partnerships. Readied catalytic frameworks that foster communication, collaboration, a shared vision, and transformative translational research across scientific and non-scientific divides are needed to foster rapid generation of novel solutions to address and ultimately eliminate disparities. To achieve this, we transformed and expanded a community-academic board into a translational science board with members from public, academic and private sectors. Rooted in team science, diverse board experts formed topic-specific “accelerators”, tasked with collaborating to rapidly generate new ideas, questions, approaches, and projects comprising patients, advocates, clinicians, researchers, funders, public health and industry leaders. We began with four accelerators—digital health, big data, genomics and environmental health—and were rapidly able to respond to funding opportunities, transform new ideas into clinical and community programs, generate new, accessible, actionable data, and more efficiently and effectively conduct research. This innovative model has the power to maximize research quality and efficiency, improve patient care and engagement, optimize data democratization and dissemination among target populations, contribute to policy, and lead to systems changes needed to address the root causes of disparities. PMID:28241508

A human language corpus for interstellar message construction

NASA Astrophysics Data System (ADS)

Elliott, John

2011-02-01

The aim of HuLCC (the human language chorus corpus), is to provide a resource of sufficient size to facilitate inter-language analysis by incorporating languages from all the major language families: for the first time all aspects of typology will be incorporated within a single corpus, adhering to a consistent grammatical classification and granularity, which historically adopt a plethora of disparate schemes. An added feature will be the inclusion of a common text element, which will be translated across all languages, to provide a precise comparable thread for detailed linguistic analysis for translation strategies and a mechanism by which these mappings can be explicitly achieved. Methods developed to solve unambiguous mappings across these languages can then be adopted for any subsequent message authored by the SETI community. Initially, it is planned to provide at least 20,000 words for each chosen language, as this amount of text exceeds the point where randomly generated text can be disambiguated from natural language and is of sufficient size useful for message transmission [1] (Elliot, 2002). This paper details the design of this resource, which ultimately will be made available to SETI upon its completion, and discusses issues 'core' to any message construction.

Accelerators: Sparking Innovation and Transdisciplinary Team Science in Disparities Research.

PubMed

Horowitz, Carol R; Shameer, Khader; Gabrilove, Janice; Atreja, Ashish; Shepard, Peggy; Goytia, Crispin N; Smith, Geoffrey W; Dudley, Joel; Manning, Rachel; Bickell, Nina A; Galvez, Maida P

2017-02-23

Development and implementation of effective, sustainable, and scalable interventions that advance equity could be propelled by innovative and inclusive partnerships. Readied catalytic frameworks that foster communication, collaboration, a shared vision, and transformative translational research across scientific and non-scientific divides are needed to foster rapid generation of novel solutions to address and ultimately eliminate disparities. To achieve this, we transformed and expanded a community-academic board into a translational science board with members from public, academic and private sectors. Rooted in team science, diverse board experts formed topic-specific "accelerators", tasked with collaborating to rapidly generate new ideas, questions, approaches, and projects comprising patients, advocates, clinicians, researchers, funders, public health and industry leaders. We began with four accelerators-digital health, big data, genomics and environmental health-and were rapidly able to respond to funding opportunities, transform new ideas into clinical and community programs, generate new, accessible, actionable data, and more efficiently and effectively conduct research. This innovative model has the power to maximize research quality and efficiency, improve patient care and engagement, optimize data democratization and dissemination among target populations, contribute to policy, and lead to systems changes needed to address the root causes of disparities.

Brittle deformation along the Gulf of Alaska margin in response to Paleocene-Eocene triple junction migration: in Sisson

USGS Publications Warehouse

Haeussler, Peter J.; Bradley, Dwight C.; Goldfarb, Richard J.

2003-01-01

A spreading center was subducted diachronously along a 2200 km segment of what is now the Gulf of Alaska margin between 61 and 50 Ma, and left in its wake near-trench intrusions and high-T, low-P metamorphic rocks. Gold-quartz veins and dikes, linked to ridge subduction by geochronological and relative timing evidence, provide a record of brittle deformation during and after passage of the ridge. The gold-quartz veins are typically hosted by faults, and their regional extent indicates there was widespread deformation of the forearc above the slab window at the time of ridge subduction. Considerable variability in the strain pattern was associated with the slab window and the trailing plate. A diffuse network of dextral, sinistral, and normal faults hosted small lode-gold deposits (<50,000 oz) in south-central Alaska, whereas crustal-scale dextral faults in southeastern Alaska are spatially associated with large gold deposits (up to 800,000 oz).We interpret the gold-quartz veins as having formed above an eastward-migrating slab window, where the forearc crust responded to the diminishing influence of the forward subducting plate, the increasing influence of the trailing plate, and the thermal pulse and decreased basal friction from the slab window. In addition, extensional deformation of the forearc resulted from the diverging motions of the two oceanic plates at the margins of the slab window. Factors that complicate interpretations of fault kinematics and near-trench dike orientations include a change in plate motions at ca. 52 Ma, northward translation of the accretionary complex, oroclinal bending of the south-central Alaska margin, and subduction of transform segments. We find the pattern of syn-ridge subduction faulting in southern Alaska is remarkably similar to brittle faults near the Chile triple junction and to earthquake focal mechanisms in the Woodlark basin - the two modern sites of ridge subduction. Therefore, extensional and strike-slip deformation above slab windows may be a common occurrence.

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization.

PubMed

Jeong, Songmi; Lee, Jong Hoon; Chung, Mi Joo; Lee, Sea Won; Lee, Jeong Won; Kang, Dae Gyu; Kim, Sung Hwan

2016-01-01

We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients.We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error.The mean ± SD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ± 3.42 mm, -0.67 ± 2.27 mm, 1.05 ± 2.87 mm, and -0.43 ± 0.89°, respectively. The mean ± SD of random error (δ) was 1.95 ± 1.60 mm in X, 1.02 ± 0.50 mm in Y, 1.01 ± 0.48 mm in Z, and 0.37 ± 0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity.The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data.

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization

PubMed Central

Jeong, Songmi; Lee, Jong Hoon; Chung, Mi Joo; Lee, Sea Won; Lee, Jeong Won; Kang, Dae Gyu; Kim, Sung Hwan

2016-01-01

Abstract We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients. We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error. The mean ± SD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ± 3.42 mm, −0.67 ± 2.27 mm, 1.05 ± 2.87 mm, and −0.43 ± 0.89°, respectively. The mean ± SD of random error (δ) was 1.95 ± 1.60 mm in X, 1.02 ± 0.50 mm in Y, 1.01 ± 0.48 mm in Z, and 0.37 ± 0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity. The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data. PMID:26765418

SU-E-T-622: Planning Technique for Passively-Scattered Involved-Node Proton Therapy of Mediastinal Lymphoma with Consideration of Cardiac Motion

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

Flampouri, S; Li, Z; Hoppe, B

2015-06-15

Purpose: To develop a treatment planning method for passively-scattered involved-node proton therapy of mediastinal lymphoma robust to breathing and cardiac motions. Methods: Beam-specific planning treatment volumes (bsPTV) are calculated for each proton field to incorporate pertinent uncertainties. Geometric margins are added laterally to each beam while margins for range uncertainty due to setup errors, breathing, and calibration curve uncertainties are added along each beam. The calculation of breathing motion and deformation effects on proton range includes all 4DCT phases. The anisotropic water equivalent margins are translated to distances on average 4DCT. Treatment plans are designed so each beam adequately coversmore » the corresponding bsPTV. For targets close to the heart, cardiac motion effects on dosemaps are estimated by using a library of anonymous ECG-gated cardiac CTs (cCT). The cCT, originally contrast-enhanced, are partially overridden to allow meaningful proton dose calculations. Targets similar to the treatment targets are drawn on one or more cCT sets matching the anatomy of the patient. Plans based on the average cCT are calculated on individual phases, then deformed to the average and accumulated. When clinically significant dose discrepancies occur between planned and accumulated doses, the patient plan is modified to reduce the cardiac motion effects. Results: We found that bsPTVs as planning targets create dose distributions similar to the conventional proton planning distributions, while they are a valuable tool for visualization of the uncertainties. For large targets with variability in motion and depth, integral dose was reduced because of the anisotropic margins. In most cases, heart motion has a clinically insignificant effect on target coverage. Conclusion: A treatment planning method was developed and used for proton therapy of mediastinal lymphoma. The technique incorporates bsPTVs compensating for all common sources of uncertainties and estimation of the effects of cardiac motion not commonly performed.« less

A true polar wander model for Neoproterozoic plate motions

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

Ripperdan, R.L.

1992-01-01

Recent paleogeographic reconstructions for the interval 750--500 Ma (Neoproterozoic to Late Cambrian) require rapid rates of plate motion and/or rotation around an equatorial Euler pole to accommodate reconstructions for the Early Paleozoic. Motions of this magnitude appear to be very uncommon during the Phanerozoic. A model for plate motions based on the hypothesis that discrete intervals of rapid true polar wander (RTPW) occurred during the Neoproterozoic can account for the paleogeographic changes with minimum amounts of plate motion. The model uses the paleogeographic reconstructions of Hoffman (1991). The following constraints were applied during derivation of the model: (1) relative motionsmore » between major continental units were restricted to be combinations of great circle or small circle translations with Euler poles of rotation = spin axis; (2) maximum rates of relative translational plate motion were 0.2 m/yr. Based on these constraints, two separate sets of synthetic plate motion trajectories were determined. The sequence of events in both can be summarized as: (1) A rapid true polar wander event of ca 90[degree] rafting a supercontinent to the spin axis; (2) breakup of the polar supercontinent into two fragments, one with the Congo, West Africa, Amazonia, and Baltica cratons, the other with the Laurentia, East Gondwana, and Kalahari cratons; (3) great circle motion of the blocks towards the equator; (4) small circle motion leading to amalgamation of Gondwana and separation of Laurentia and Baltica. In alternative 1, rifting initiates between East Antarctica and Laurentia and one episode of RTPW is required. Alternative 2 requires two episodes of RTPW; and that rifting occurred first along the eastern margin and later along the western margin of Laurentia. Synthetic plate motion trajectories are compared to existing paleomagnetic and geological data, and implications of the model for paleoclimatic changes during the Neoproterozoic are discussed.« less

The influence of novel compliant floors on balance control in elderly women--A biomechanical study.

PubMed

Wright, Alexander D; Laing, Andrew C

2011-07-01

Novel compliant floors aim to decrease the risk for fall-related injury by providing substantial force attenuation during the impact phase of falls. Certain models of compliant flooring have been shown to have limited influence on postural sway and successful completion of dynamic balance tasks. However, the effects of these products on balance recovery mechanisms following an externally induced perturbation have yet to be quantified. We used a floor translation paradigm to induce a balance perturbation to thirteen elderly community-dwelling women. Outcome measures included the displacement rates and margins of safety for both the underfoot centre-of-pressure and whole-body centre-of-mass across two novel compliant floors (SmartCell, SofTile), two basic foam surfaces (Firm-Foam, Soft-Foam) and a standard 'Rigid' floor as a control condition. The centre-of-mass and centre-of-pressure margins of safety, and all centre-of-mass displacement rates, were not significantly lower for the two novel compliant flooring systems compared to the control floor. The centre-of-pressure displacement rates were similar to the control floor for the SmartCell floor condition. The majority of the margin of safety and displacement rate variables for the foam floors were significantly lower than the control condition. This study illustrates that the SmartCell and SofTile novel compliant floors have minimal influences on balance and balance control responses following externally induced perturbations in older community-dwelling women, and supports pilot installations of these floors to inform decisions regarding the development of clinical trials. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

The influence of novel compliant floors on balance control in elderly women—A biomechanical study

PubMed Central

Wright, Alexander D.; Laing, Andrew C.

2012-01-01

Novel compliant floors aim to decrease the risk for fall-related injury by providing substantial force attenuation during the impact phase of falls. Certain models of compliant flooring have been shown to have limited influence on postural sway and successful completion of dynamic balance tasks. However, the effects of these products on balance recovery mechanisms following an externally induced perturbation have yet to be quantified. We used a floor translation paradigm to induce a balance perturbation to thirteen elderly community-dwelling women. Outcome measures included the displacement rates and margins of safety for both the underfoot centre-of-pressure and whole-body centre-of-mass across two novel compliant floors (Smart-Cell, SofTile), two basic foam surfaces (Firm-Foam, Soft-Foam) and a standard ‘Rigid’ floor as a control condition. The centre-of-mass and centre-of-pressure margins of safety, and all centre-of-mass displacement rates, were not significantly lower for the two novel compliant flooring systems compared to the control floor. The centre-of-pressure displacement rates were similar to the control floor for the SmartCell floor condition. The majority of the margin of safety and displacement rate variables for the foam floors were significantly lower than the control condition. This study illustrates that the SmartCell and SofTile novel compliant floors have minimal influences on balance and balance control responses following externally induced perturbations in older community-dwelling women, and supports pilot installations of these floors to inform decisions regarding the development of clinical trials. PMID:21545881

Plate Margin Deformation and Active Tectonics Along the Northern Edge of the Yakutat Terrane in the Saint Elias Orogen, Alaska and Yukon, Canada

NASA Technical Reports Server (NTRS)

Bruhn, Ronald L.; Sauber, Jeanne; Cotton, Michele M.; Pavlis, Terry L.; Burgess, Evan; Ruppert, Natalia; Forster, Richard R.

2012-01-01

The northwest directed motion of the Pacific plate is accompanied by migration and collision of the Yakutat terrane into the cusp of southern Alaska. The nature and magnitude of accretion and translation on upper crustal faults and folds is poorly constrained, however, due to pervasive glaciation. In this study we used high-resolution topography, geodetic imaging, seismic, and geologic data to advance understanding of the transition from strike-slip motion on the Fairweather fault to plate margin deformation on the Bagley fault, which cuts through the upper plate of the collisional suture above the subduction megathrust. The Fairweather fault terminates by oblique-extensional splay faulting within a structural syntaxis, allowing rapid tectonic upwelling of rocks driven by thrust faulting and crustal contraction. Plate motion is partly transferred from the Fairweather to the Bagley fault, which extends 125 km farther west as a dextral shear zone that is partly reactivated by reverse faulting. The Bagley fault dips steeply through the upper plate to intersect the subduction megathrust at depth, forming a narrow fault-bounded crustal sliver in the obliquely convergent plate margin. Since . 20 Ma the Bagley fault has accommodated more than 50 km of dextral shearing and several kilometers of reverse motion along its southern flank during terrane accretion. The fault is considered capable of generating earthquakes because it is linked to faults that generated large historic earthquakes, suitably oriented for reactivation in the contemporary stress field, and locally marked by seismicity. The fault may generate earthquakes of Mw <= 7.5.

The fractal heart — embracing mathematics in the cardiology clinic

PubMed Central

Captur, Gabriella; Karperien, Audrey L.; Hughes, Alun D.; Francis, Darrel P.; Moon, James C.

2017-01-01

For clinicians grappling with quantifying the complex spatial and temporal patterns of cardiac structure and function (such as myocardial trabeculae, coronary microvascular anatomy, tissue perfusion, myocyte histology, electrical conduction, heart rate, and blood-pressure variability), fractal analysis is a powerful, but still underused, mathematical tool. In this Perspectives article, we explain some fundamental principles of fractal geometry and place it in a familiar medical setting. We summarize studies in the cardiovascular sciences in which fractal methods have successfully been used to investigate disease mechanisms, and suggest potential future clinical roles in cardiac imaging and time series measurements. We believe that clinical researchers can deploy innovative fractal solutions to common cardiac problems that might ultimately translate into advancements for patient care. PMID:27708281

You have an idea, now what?

PubMed

Gertner, Michael

2006-11-01

The innovation process is often more important than the original idea, particularly when the ultimate goal is to improve patient care through technologically advanced products. Many physicians have great ideas; unfortunately, many of these great ideas are never translated to patient care improvements because of a misunderstanding of "the next step." In many cases, the next step is a step backward to understand the real clinical problem: "the clinical need." With the clinical need in hand, the most efficient path to a product for improved patient care can then be derived. Often, the most efficient pathway involves an appreciation of many issues, including intellectual property, regulatory pathways, finance, and clinical trial strategies. The integration of these issues underlies innovation in biomedical technology.

Can platelet-rich plasma enhance anterior cruciate ligament and meniscal repair?

PubMed

Hutchinson, Ian D; Rodeo, Scott A; Perrone, Gabriel S; Murray, Martha M

2015-02-01

The use of platelet-rich plasma (PRP) to improve clinical outcome following a soft tissue injury, regeneration, and repair has been the subject of intense investigation and discussion. This article endeavors to relate clinical and basic science strategies focused on biological augmentation of the healing response in anterior cruciate ligament (ACL) and meniscus repair and replacement using PRP. Therein, a translational feedback loop is created in the literature and targeted towards the entire multidisciplinary team. Ultimately, it is hoped that the theoretical benefits of PRP on soft-tissue interfacial healing will emerge clinically following a careful, focused characterization at the benchtop, and prospective randomized controlled clinical study. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24-25, 2015. Workshop Report.

PubMed

Kager, Leo; Whelan, Jeremy; Dirksen, Uta; Hassan, Bass; Anninga, Jakob; Bennister, Lindsey; Bovée, Judith V M G; Brennan, Bernadette; Broto, Javier M; Brugières, Laurence; Cleton-Jansen, Anne-Marie; Copland, Christopher; Dutour, Aurélie; Fagioli, Franca; Ferrari, Stefano; Fiocco, Marta; Fleuren, Emmy; Gaspar, Nathalie; Gelderblom, Hans; Gerrand, Craig; Gerß, Joachim; Gonzato, Ornella; van der Graaf, Winette; Hecker-Nolting, Stefanie; Herrero-Martín, David; Klco-Brosius, Stephanie; Kovar, Heinrich; Ladenstein, Ruth; Lancia, Carlo; LeDeley, Marie-Cecile; McCabe, Martin G; Metzler, Markus; Myklebost, Ola; Nathrath, Michaela; Picci, Piero; Potratz, Jenny; Redini, Françoise; Richter, Günther H S; Reinke, Denise; Rutkowski, Piotr; Scotlandi, Katia; Strauss, Sandra; Thomas, David; Tirado, Oscar M; Tirode, Franck; Vassal, Gilles; Bielack, Stefan S

2016-01-01

This report summarizes the results of the 3rd Joint ENCCA-WP7, EuroSarc, EEC, PROVABES, and EURAMOS European Bone Sarcoma Network Meeting, which was held at the Children's Cancer Research Institute in Vienna, Austria on September 24-25, 2015. The joint bone sarcoma network meetings bring together European bone sarcoma researchers to present and discuss current knowledge on bone sarcoma biology, genetics, immunology, as well as results from preclinical investigations and clinical trials, to generate novel hypotheses for collaborative biological and clinical investigations. The ultimate goal is to further improve therapy and outcome in patients with bone sarcomas.

“Scar-cinoma”: viewing the fibrotic lung mesenchymal cell in the context of cancer biology

PubMed Central

Horowitz, Jeffrey C.; Osterholzer, John J.; Marazioti, Antonia; Stathopoulos, Georgios T.

2017-01-01

Lung cancer and pulmonary fibrosis are common, yet distinct, pathological processes that represent urgent unmet medical needs. Striking clinical and mechanistic parallels exist between these distinct disease entities. The goal of this article is to examine lung fibrosis from the perspective of cancer-associated phenotypic hallmarks, to discuss areas of mechanistic overlap and distinction, and to highlight profibrotic mechanisms that contribute to carcinogenesis. Ultimately, we speculate that such comparisons might identify opportunities to leverage our current understanding of the pathobiology of each disease process in order to advance novel therapeutic approaches for both. We anticipate that such “outside the box” concepts could be translated to a more precise and individualised approach to fibrotic diseases of the lung. PMID:27030681

Across Europe to CERN: Taking students on the ultimate physics experience

NASA Astrophysics Data System (ADS)

Wheeler, Sam

2018-05-01

In 2013, I was an Einstein Fellow with the U.S. Department of Energy and I was asked by a colleague, working in a senator's office, if I would join him in a meeting with a physicist to "translate" the science into something more understandable. That meeting turned out to be a wonderful opportunity I would never have otherwise had. During the meeting I met Michael Tuts, a physicist who was working on project ATLAS at CERN. Afterwards, I walked with him out of the Senate office building to Union Station and, in parting, he gave me his card and told me that if I were in Geneva that he could help me get a tour of CERN and the LHC.

Engineering clinically relevant volumes of vascularized bone

PubMed Central

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-01-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. PMID:25877690

A Journey in Science: Promise, Purpose, Privilege

PubMed Central

Nathan, Carl

2013-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the first Cerami Award Monograph, by Carl Nathan, MD, chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College, reflects towering genius and soaring inspiration. PMID:24089245

A journey in science: promise, purpose, privilege.

PubMed

Nathan, Carl

2013-10-03

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the first Cerami Award Monograph, by Carl Nathan, MD, chairman of the Department of Microbiology and Immunology at Weill Cornell Medical College, reflects towering genius and soaring inspiration.

Nahcolite and halite deposition through time during the saline mineral phase of Eocene Lake Uinta, Piceance Basin, western Colorado

USGS Publications Warehouse

Johnson, Ronald C.; Brownfield, Michael E.

2013-01-01

Halite and the sodium bicarbonate mineral nahcolite were deposited during the saline phase of Eocene Lake Uinta in the Piceance Basin, western Colorado. Variations in the area of saline mineral deposition through time were interpreted from studies of core and outcrop. Saline minerals were extensively leached by groundwater, so the original extent of saline deposition was estimated from the distribution of empty vugs and collapse breccias. Vugs and breccias strongly influence groundwater movement, so determining where leaching has occurred is an important consideration for in-situ oil shale extraction methods currently being developed. Lake Uinta formed when two smaller fresh water lakes, one in the Uinta Basin of eastern Utah and the other in the Piceance Basin of western Colorado, expanded and coalesced across the Douglas Creek arch, an area of comparatively low subsidence rates. Salinity increased shortly after this expansion, but saline mineral deposition did not begin until later, after a period of prolonged infilling created broad lake-margin shelves and a comparatively small deep central lake area. These shelves probably played a critical role in brine evolution. A progression from disseminated nahcolite and nahcolite aggregates to bedded nahcolite and ultimately to bedded nahcolite and halite was deposited in this deep lake area during the early stages of saline deposition along with rich oil shale that commonly shows signs of slumping and lateral transport. The area of saline mineral and rich oil shale deposition subsequently expanded, in part due to infilling of the compact deep area, and in part because of an increase in water flow into Lake Uinta, possibly due to outflow from Lake Gosiute to the north. Finally, as Lake Uinta in the Piceance Basin was progressively filled from north to south by volcano-clastic sediment, the saline depocenter was pushed progressively southward, eventually covering much of the areas that had previously been marginal shelves. A saline depocenter formed in the eastern Uinta Basin during this progradation, and saline minerals were deposited in both basins for a time. Ultimately, the saline depocenter in the Piceance Basin was completely filled in and saline mineral deposition shifted entirely into the Uinta Basin.

Relative importance of physical and economic factors in Appalachian coalbed gas assessment

USGS Publications Warehouse

Attanasi, E.D.

1998-01-01

In the 1995 National Assessment of Oil and Gas Resources prepared by the U.S. Geological Survey, only 20% of the assessed technically recoverable Appalachian Province coalbed gas resources were economic. Physical and economic variables are examined to explain the disparity between economic and technically recoverable coalbed gas. The Anticline and Syncline plays of the Northern Appalachian Basin, which account for 77% of the assessed technically recoverable coalbed gas, are not economic. Analysis shows marginal reductions in costs or rate of return will not turn these plays into commercial successes. Physical parameters that determine ultimate well recoverability and the rate of gas recovery are primary reasons the Northern Appalachian Basin plays are non-commercial. If the application of new well stimulation technology could offset slow gas desorption rates, Appalachian Province economic gas could increase to more then 70% of the technically recoverable gas. Similarly, if operators are able to develop strategies to selectively drill plays by avoiding dry holes and non-commercial occurrences, the economic fraction of technically recoverable gas could increase to over half.In the 1995 National Assessment of Oil and Gas Resources prepared by the U.S. Geological Survey, only 20% of the assessed technically recoverable Appalachian Province coalbed gas resources were economic. Physical and economic variables are examined to explain the disparity between economic and technically recoverable coalbed gas. The Anticline and Syncline plays of the Northern Appalachian Basin, which account for 77% of the assessed technically recoverable coalbed gas, are not economic. Analysis shows marginal reductions in costs or rate of return will not turn these plays into commercial successes. Physical parameters that determine ultimate well recoverability and the rate of gas recovery are primary reasons the Northern Appalachian Basin plays are non-commercial. If the application of new well stimulation technology could offset slow gas desorption rates, Appalachian Province economic gas could increase to more then 70% of the technically recoverable gas. Similarly, if operators are able to develop strategies to selectively drill plays by avoiding dry holes and non-commercial occurrences, the economic fraction of technically recoverable gas could increase to over half.

Application of the Intervention Mapping Framework to Develop an Integrated Twenty-first Century Core Curriculum—Part Two: Translation of MPH Core Competencies into an Integrated Theory-Based Core Curriculum

PubMed Central

Corvin, Jaime A.; DeBate, Rita; Wolfe-Quintero, Kate; Petersen, Donna J.

2017-01-01

In the twenty-first century, the dynamics of health and health care are changing, necessitating a commitment to revising traditional public health curricula to better meet present day challenges. This article describes how the College of Public Health at the University of South Florida utilized the Intervention Mapping framework to translate revised core competencies into an integrated, theory-driven core curriculum to meet the training needs of the twenty-first century public health scholar and practitioner. This process resulted in the development of four sequenced courses: History and Systems of Public Health and Population Assessment I delivered in the first semester and Population Assessment II and Translation to Practice delivered in the second semester. While the transformation process, moving from traditional public health core content to an integrated and innovative curriculum, is a challenging and daunting task, Intervention Mapping provides the ideal framework for guiding this process. Intervention mapping walks the curriculum developers from the broad goals and objectives to the finite details of a lesson plan. Throughout this process, critical lessons were learned, including the importance of being open to new ideologies and frameworks and the critical need to involve key-stakeholders in every step of the decision-making process to ensure the sustainability of the resulting integrated and theory-based curriculum. Ultimately, as a stronger curriculum emerged, the developers and instructors themselves were changed, fostering a stronger public health workforce from within. PMID:29164094

Chinese translation and validation of a parental feeding style questionnaire for parents of Hong Kong preschoolers.

PubMed

Tam, Wilson; Keung, Vera; Lee, Albert; Lo, Kenneth; Cheung, Calvin

2014-11-21

Childhood obesity is a major public health issue in many countries, including China. The importance of parenting relative to the healthy development of children requires the development of instruments for assessing parental influence on child dietary pattern. This study aimed to confirm the internal reliability and validity of a self-report measure on parental feeding styles, including emotional feeding, instrumental feeding, prompting or encouragement to eat, and control over eating. A 27-item parental feeding style questionnaire (PFSQ) was translated into Chinese and then translated back into English to verify consistency. The questionnaire was then used to conduct a cross-sectional survey on the parents of Hong Kong preschoolers. The internal reliability and validity of the questionnaire were examined by Cronbach's alpha and exploratory factor analysis, respectively. 4,553 completed questionnaires were received. Cronbach's alpha of subscales ranged from 0.63 to 0.81, and the overall reliability was good (alpha = 0.75). The factor structure of this questionnaire was similar to that of the original and Turkish versions. One-factor structure was identified for emotional feeding, instrumental feeding (four items), and prompting or encouragement to eat, whereas a two-factor structure was revealed for control over eating. The Chinese version of the PFSQ has good reliability and validity in assessing parental feeding styles in Hong Kong. Researchers can use this instrument to improve their understanding on how parental feeding styles may affect the dietary patterns and ultimately the weight statuses of children among Chinese-speaking populations across different countries.

Translating Cough Mechanisms Into Better Cough Suppressants.

PubMed

Keller, Jennifer A; McGovern, Alice E; Mazzone, Stuart B

2017-10-01

Chronic cough is a significant problem, and in many patients cough remains refractive to both disease-specific therapies and current cough-suppressing medicines, creating a need for improved antitussive therapies. Most patients with chronic cough also display heightened sensitivity so that they experience a persistent sense of the need to cough, and often innocuous stimuli can trigger their coughing. This hypersensitivity underpins the newly described concept of cough hypersensitivity syndrome (CHS), a term that encapsulates the notion of common underlying mechanisms producing neuronal activation, sensitization and/or dysfunction, which are at the core of excessive coughing. Understanding these mechanisms has been a focus of recent research efforts in the field in the hope that new therapies can be developed to selectively target sensitized unproductive cough while maintaining the reflexive cough essential for airway protection. However, efforts to achieve this have been slower than expected, in part because of some significant challenges and limitations translating current cough models. In this review, we summarize recent advances in our understanding of the sensory circuits innervating the respiratory system that are important for cough, how cough sensory pathways become hypersensitive, and some of the recently described neural targets under development for treating chronic cough. We present the case that better use of current cough models or the development of new models, or both, is ultimately needed to advance our efforts to translate the discovery of basic cough mechanisms into effective medicines for treating patients with chronic cough. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Animal Models in Genomic Research: Techniques, Applications, and Roles for Nurses

PubMed Central

Osier, Nicole D.; Pham, Lan; Savarese, Amanda; Sayles, Kendra

2016-01-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. PMID:27969037

Nursing Unit Environment Associated with Provision of Language Services in Pediatric Hospices.

PubMed

Lindley, Lisa C; Held, Mary L; Henley, Kristen M; Miller, Kathryn A; Pedziwol, Katherine E; Rumley, Laurie E

2017-04-01

Provision of language services in pediatric hospice enables nurses to communicate effectively with patients who have limited English proficiency. Language barriers contribute to ethnic disparities in health care. While language service use corresponds with improved patient comprehension of illness and care options, we lack an understanding of how the nurse work environment affects the provision of these services. Data were obtained from the 2007 National Home and Hospice Care Survey and included a study sample of 1251 pediatric hospice agencies. Variable selection was guided by structural contingency theory, which posits that organizational effectiveness is dependent upon how well an organization's structure relates to its context. Using multivariate logistic regression, we analyzed the extent to which nursing unit environment predicted provision of translation services and interpreter services. The majority of hospices provided translation services (74.9 %) and interpreter services (87.1 %). Four variables predicted translation services: registered nurse (RN) unit size, RN leadership, RN medical expertise, and for-profit status. RN medical expertise and having a safety climate within the hospice corresponded with provision of interpreter services. Findings indicate that nursing unit environment predicts provision of language services. Hospices with more specialized RNs and a stronger safety climate might include staffs who are dedicated to best care provision, including language services. This study provides valuable data on the nurse work environment as a predictor of language services provision, which can better serve patients with limited English proficiency and ultimately reduce ethnic disparities in end-of-life care for children and their families.

Nursing unit environment associated with provision of language services in pediatric hospices

PubMed Central

Lindley, Lisa C.; Held, Mary L.; Henley, Kristen M.; Miller, Kathryn A.; Pedziwol, Katherine E.; Rumley, Laurie E.

2016-01-01

Background Provision of language services in pediatric hospice enables nurses to communicate effectively with patients who have limited English proficiency. Language barriers contribute to ethnic disparities in health care. While language service use corresponds with improved patient comprehension of illness and care options, we lack an understanding of how the nurse work environment affects the provision of these services. Methods Data were obtained from the 2007 National Home and Hospice Care Survey and included a study sample of 1,251 pediatric hospice agencies. Variable selection was guided by Structural Contingency Theory, which posits that organizational effectiveness is dependent upon how well an organization’s structure relates to its context. Using multivariate logistic regression, we analyzed the extent to which nursing unit environment predicted provision of translation services and interpreter services. Results The majority of hospices provided translation services (74.9%) and interpreter services (87.1%). Four variables predicted translation services: registered nurse (RN) unit size, RN leadership, RN medical expertise, and for-profit status. RN medical expertise and having a safety climate within the hospice corresponded with provision of interpreter services. Conclusions Findings indicate that nursing unit environment predict provision of language services. Hospices with more specialized RNs and a stronger safety climate might include staff who are dedicated to best care provision, including language services. This study provides valuable data on the nurse work environment as a predictor of language services provision, which can better serve patients with limited English proficiency, and ultimately reduce ethnic disparities in end-of-life care for children and their families. PMID:27059050

Animal models in genomic research: Techniques, applications, and roles for nurses.

PubMed

Osier, Nicole D; Pham, Lan; Savarese, Amanda; Sayles, Kendra; Alexander, Sheila A

2016-11-01

Animal research has been conducted by scientists for over two millennia resulting in a better understanding of human anatomy, physiology, and pathology, as well as testing of novel therapies. In the molecular genomic era, pre-clinical models represent a key tool for understanding the genomic underpinnings of health and disease and are relevant to precision medicine initiatives. Nurses contribute to improved health by collecting and translating evidence from clinically relevant pre-clinical models. Using animal models, nurses can ask questions that would not be feasible or ethical to address in humans, and establish the safety and efficacy of interventions before translating them to clinical trials. Two advantages of using pre-clinical models are reduced variability between test subjects and the opportunity for precisely controlled experimental exposures. Standardized care controls the effects of diet and environment, while the availability of inbred strains significantly reduces the confounding effects of genetic differences. Outside the laboratory, nurses can contribute to the approval and oversight of animal studies, as well as translation to clinical trials and, ultimately, patient care. This review is intended as a primer on the use of animal models to advance nursing science; specifically, the paper discusses the utility of preclinical models for studying the pathophysiologic and genomic contributors to health and disease, testing interventions, and evaluating effects of environmental exposures. Considerations specifically geared to nurse researchers are also introduced, including discussion of how to choose an appropriate model and controls, potential confounders, as well as legal and ethical concerns. Finally, roles for nurse clinicians in pre-clinical research are also highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

Geochemistry of Permian rocks from the margins of the Phosphoria Basin

USGS Publications Warehouse

Perkins, Robert B.; McIntyre, Brandie; Hein, James R.; Piper, David Z.

2003-01-01

The Permian Phosphoria Formation and interbedded units of the Park City Formation and Shedhorn Sandstone in western Wyoming represent deposition along a carbonate ramp at the eastern margin of the Phosphoria Basin, with portions of the Phosphoria units reflecting periods of upwelling and widespread phosphogenesis. Thickness-weighted slab-samples of these units were collected at a maximum interval of 3 m along an 80+ m-length of unweathered core and analyzed for major-, minor-, and trace-element contents. Interpretations of geochemistry were made within the confines of a previously recognized sequence stratigraphy framework. Major shifts in element ratios characteristic of terrigenous debris that occur at sequence boundaries at the base of the Meade Peak and Retort Members of the Phosphoria Formation are attributed to changing sediment sources. Inter-element relationships in the marine fraction indicate that bottom waters of the Phosphoria Basin were predominantly denitrifying during deposition of the Ervay, Grandeur, and Phosphoria sediments, although sulfate-reducing conditions may have existed during deposition of the lower Meade Peak sediments. Oxic conditions were prevalent during deposition of a large part of the Franson Member, which represents sedimentation in a shallow, inner- to back-ramp setting. Variations in sediment facies and organic matter and trace element contents largely reflect changes in Permian sea level. Changes in sea level in basin-margin areas, such as represented by the study section, may have affected the oxidation of settling organic matter, the foci of intersection of upwelling bottom waters with the photic zone, the rate of terrigenous sedimentation, and, ultimately, the overall environment of deposition. Our study suggests that phosphogenesis can occur under lowstand, transgressive, and highstand conditions in marginal areas, assuming water depths sufficient for upwelling to occur. Formation of phosphorite layers under upwelling conditions appears to have been most dependent on a lack of dilution by terrigenous sedimentation and carbonate shoaling. Differences in the geochemistry between two similar environments represented by the upper and lower Phosphoria units are largely attributed to higher rates of diluting terrigenous sediment during deposition of the upper unit. This is consistent with prior interpretations of a more shoreward setting for the upper Phosphoria.

Design, implementation, and evaluation of a knowledge translation intervention to increase organ donation after cardiocirculatory death in Canada: a study protocol.

PubMed

Squires, Janet E; Grimshaw, Jeremy M; Taljaard, Monica; Linklater, Stefanie; Chassé, Michaël; Shemie, Sam D; Knoll, Gregory A

2014-06-20

A shortage of transplantable organs is a global problem. There are two types of organ donation: living and deceased. Deceased organ donation can occur following neurological determination of death (NDD) or cardiocirculatory death. Donation after cardiocirculatory death (DCD) accounts for the largest increments in deceased organ donation worldwide. Variations in the use of DCD exist, however, within Canada and worldwide. Reasons for these discrepancies are largely unknown. The purpose of this study is to develop, implement, and evaluate a theory-based knowledge translation intervention to provide practical guidance about how to increase the numbers of DCD organ donors without reducing the numbers of standard NDD donors. We will use a mixed method three-step approach. In step one, we will conduct semi-structured interviews, informed by the Theoretical Domains Framework, to identify and describe stakeholders' beliefs and attitudes about DCD and their perceptions of the multi-level factors that influence DCD. We will identify: determinants of the evidence-practice gap; specific behavioural changes and/or process changes needed to increase DCD; specific group(s) of clinicians or organizations (e.g., provincial donor organizations) in need of behaviour change; and specific targets for interventions. In step two, using the principles of intervention mapping, we will develop a theory-based knowledge translation intervention that encompasses behavior change techniques to overcome the identified barriers and enhance the enablers to DCD. In step three, we will roll out the intervention in hospitals across the 10 Canadian provinces and evaluate its effectiveness using a multiple interrupted time series design. We will adopt a behavioural approach to define and test novel, theory-based, and ethically-acceptable knowledge translation strategies to increase the numbers of available DCD organ donors in Canada. If successful, this study will ultimately lead to more transplantations, reducing patient morbidity and mortality at a population-level.

Design, implementation, and evaluation of a knowledge translation intervention to increase organ donation after cardiocirculatory death in Canada: a study protocol

PubMed Central

2014-01-01

Background A shortage of transplantable organs is a global problem. There are two types of organ donation: living and deceased. Deceased organ donation can occur following neurological determination of death (NDD) or cardiocirculatory death. Donation after cardiocirculatory death (DCD) accounts for the largest increments in deceased organ donation worldwide. Variations in the use of DCD exist, however, within Canada and worldwide. Reasons for these discrepancies are largely unknown. The purpose of this study is to develop, implement, and evaluate a theory-based knowledge translation intervention to provide practical guidance about how to increase the numbers of DCD organ donors without reducing the numbers of standard NDD donors. Methods We will use a mixed method three-step approach. In step one, we will conduct semi-structured interviews, informed by the Theoretical Domains Framework, to identify and describe stakeholders’ beliefs and attitudes about DCD and their perceptions of the multi-level factors that influence DCD. We will identify: determinants of the evidence-practice gap; specific behavioural changes and/or process changes needed to increase DCD; specific group(s) of clinicians or organizations (e.g., provincial donor organizations) in need of behaviour change; and specific targets for interventions. In step two, using the principles of intervention mapping, we will develop a theory-based knowledge translation intervention that encompasses behavior change techniques to overcome the identified barriers and enhance the enablers to DCD. In step three, we will roll out the intervention in hospitals across the 10 Canadian provinces and evaluate its effectiveness using a multiple interrupted time series design. Discussion We will adopt a behavioural approach to define and test novel, theory-based, and ethically-acceptable knowledge translation strategies to increase the numbers of available DCD organ donors in Canada. If successful, this study will ultimately lead to more transplantations, reducing patient morbidity and mortality at a population-level. PMID:24950719

Image-derived input function in PET brain studies: blood-based methods are resistant to motion artifacts.

PubMed

Zanotti-Fregonara, Paolo; Liow, Jeih-San; Comtat, Claude; Zoghbi, Sami S; Zhang, Yi; Pike, Victor W; Fujita, Masahiro; Innis, Robert B

2012-09-01

Image-derived input function (IDIF) from carotid arteries is an elegant alternative to full arterial blood sampling for brain PET studies. However, a recent study using blood-free IDIFs found that this method is particularly vulnerable to patient motion. The present study used both simulated and clinical [11C](R)-rolipram data to assess the robustness of a blood-based IDIF method (a method that is ultimately normalized with blood samples) with regard to motion artifacts. The impact of motion on the accuracy of IDIF was first assessed with an analytical simulation of a high-resolution research tomograph using a numerical phantom of the human brain, equipped with internal carotids. Different degrees of translational (from 1 to 20 mm) and rotational (from 1 to 15°) motions were tested. The impact of motion was then tested on the high-resolution research tomograph dynamic scans of three healthy volunteers, reconstructed with and without an online motion correction system. IDIFs and Logan-distribution volume (VT) values derived from simulated and clinical scans with motion were compared with those obtained from the scans with motion correction. In the phantom scans, the difference in the area under the curve (AUC) for the carotid time-activity curves was up to 19% for rotations and up to 66% for translations compared with the motionless simulation. However, for the final IDIFs, which were fitted to blood samples, the AUC difference was 11% for rotations and 8% for translations. Logan-VT errors were always less than 10%, except for the maximum translation of 20 mm, in which the error was 18%. Errors in the clinical scans without motion correction appeared to be minor, with differences in AUC and Logan-VT always less than 10% compared with scans with motion correction. When a blood-based IDIF method is used for neurological PET studies, the motion of the patient affects IDIF estimation and kinetic modeling only minimally.

Paleozoic and Lower Mesozoic magmas from the eastern Klamath Mountains (North California) and the geodynamic evolution of northwestern America

NASA Astrophysics Data System (ADS)

Lapierre, H.; Brouxel, M.; Albarede, F.; Coulin, C.; Lecuyer, C.; Martin, P.; Mascle, G.; Rouer, O.

1987-09-01

The Paleozoic to Early Mesozoic geology of the eastern Klamath Mountains (N California) is characterized by three major magmatic events of Ordovician, Late Ordovician to Early Devonian, and Permo-Triassic ages. The Ordovician event is represented by a calc-alkalic island-arc sequence (Lovers Leap Butte sequence) developed in the vicinity of a continental margin. The Late Ordovician to Early Devonian event consists of the 430-480 Ma old Trinity ophiolite formed during the early development of a marginal basin, and a series of low-K tholeiitic volcanic suites (Lovers Leap Basalt—Keratophyre unit, Copley and Balaklala Formations) belonging to intraoceanic island-arcs. Finally, the Permo-Triassic event gave rise to three successives phases of volcanic activity (Nosoni, Dekkas and Bully Hill) represented by the highly differentiated basalt-to-rhyolite low-K tholeiitic series of mature island-arcs. The Permo-Triassic sediments are indicative of shallow to moderate depth in an open, warm sea. The geodynamic evolution of the eastern Klamath Mountains during Paleozoic to Early Mesozoic times is therefore constrained by the geological, petrological and geochemical features of its island-arcs and related marginal basin. A consistent plate-tectonic model is proposed for the area, consisting of six main stages: (1) development during Ordovician times of a calc-alkalic island-arc in the vicinity of a continental margin; (2) extrusion during Late Ordovician to Silurian times of a primitive basalt-andesite intraoceanic island-arc suite, which terminated with boninites, the latter suggest rifting in the fore-arc, followed by the breakup of the arc; (3) opening and development of the Trinity back-arc basin around 430-480 Ma ago; (4) eruption of the Balaklala Rhyolite either in the arc or in the fore-arc, ending in Early Devonian time with intrusion of the 400 Ma Mule Mountain stock; (5) break in volcanic activity from the Early Devonian to the Early Permian; and (6) development of a mature island-arc from the Early Permian to the Late Triassic. The eastern Klamath Mountains island-arc formations and ophiolitic suite are part of the "Cordilleran suspect terranes", considered to be Gondwana margin fragments, that have undergone large northward translations before final collision with the North American craton during Late Mesozoic or Cenozoic times. These eastern Klamath Mountains island-arcs could be associated with the paleo-Pacific oceanic plate that led to accretion of these allochthonous terranes to the American margin.

Hydrogen-oxygen proton-exchange membrane fuel cells and electrolyzers

NASA Technical Reports Server (NTRS)

Baldwin, R.; Pham, M.; Leonida, A.; Mcelroy, J.; Nalette, T.

1989-01-01

Hydrogen-oxygen SPE fuel cells and SPE electrolyzers (products of Hamilton Standard) both use a Proton-Exchange Membrane (PEM) as the sole electrolyte. The SPE cells have demonstrated a ten year life capability under load conditions. Ultimate life of PEM fuel cells and electrolyzers is primarily related to the chemical stability of the membrane. For perfluorocarbon proton-exchange membranes an accurate measure of the membrane stability is the fluoride loss rate. Millions of cell hours have contributed to establishing a relationship between fluroride loss rates and average expected ultimate cell life. Several features were introduced into SPE fuel cells and SPE electrolyzers such that applications requiring greater than or equal to 100,000 hours of life can be considered. Equally important as the ultimate life is the voltage stability of hydrogen-oxygen fuel cells and electrolyzers. Here again the features of SPE fuel cells and SPE electrolyzers have shown a cell voltage stability in the order of 1 microvolt per hour. That level of stability were demonstrated for tens of thousands of hours in SPE fuel cells at up to 500 amps per square foot (ASF) current density. The SPE electrolyzers have demonstrated the same at 1000 ASF. Many future extraterrestrial applications for fuel cells require that they be self recharged. To translate the proven SPE cell life and stability into a highly reliable extraterrestrial electrical energy storage system, a simplification of supporting equipment is required. Static phase separation, static fluid transport and static thermal control will be most useful in producting required system reliability. Although some 200,000 SPE fuel cell hours were recorded in earth orbit with static fluid phase separation, no SPE electrolyzer has, as yet, operated in space.

Hypersonic vehicle control law development using H(infinity) and micron-synthesis

NASA Technical Reports Server (NTRS)

Gregory, Irene M.; Mcminn, John D.; Shaughnessy, John D.; Chowdhry, Rajiv S.

1993-01-01

Hypersonic vehicle control law development using H(infinity) and mu-synthesis is discussed. Airbreathing SSTO vehicles has a mutli-faceted mission that includes orbital operations, as well as re-entry and descent culminating in horizontal landing. However, the most challenging part of the operations is the ascent to orbit. The airbreathing propulsion requires lengthy atmospheric flight that may last as long as 30 minutes and take the vehicle half way around the globe. The vehicles's ascent is characterized by tight payload to orbit margins which translate into minimum fuel orbit as the performance criteria. Issues discussed include: SSTO airbreathing vehicle issues; control system performance requirements; robust control law framework; H(infinity) controller frequency analysis; and mu controller frequency analysis.

Channeling Polyolefin Molecular Structure - Bulk Property Correlation Strategies for Industrial Applicability

NASA Astrophysics Data System (ADS)

Hule, Rohan; Thurman, Derek; Doufas, Antonios

Polyolefins occupy a significant volume of the polymer products portfolio in commodity and high value applications. Quantifying and optimizing structure-property relationships enables growth in new markets. It is well recognized that coupling lab-based, comprehensive methodologies with bulk properties of interest to industrial environments offer the greatest potential of technology advancement, ultimately leading to commercial success. It is imperative to recognize the existing gap of knowledge translation between lab measurements and industrial-scale operability. This study highlights experimental HDPEs synthesized from dual, single-site, co-supported catalysts that exhibit enhanced solid-state properties such as stiffness, impact and ESCR surpassing conventional trends. Commercial resins across distinct sub-families were included as well. Commonality amongst these resins is bimodality and broad MW distribution with well-defined splits and spreads. Investigations on commercially relevant parameters such as melt strength, melt elasticity and shear thinning established excellent performance for experimental bimodals, corroborating potential benefits compared to commercial HDPEs. To summarize, the effort highlights well-recognized pathways such as improvements in mechanical and melt properties that can be attributed to apposite tuning of polymer chain architecture and MW distribution with implications across myriad markets. Ultimately, this may serve as a pathway for producing innovative products that deliver business success and growth.

Contending ideologies and politico-economic philosophies underlying energy policy in the United States

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

Bucknell, H. III

1976-01-01

The energy problem besetting this country comprises economic, technological, and physical (geologic) factors--but the solutions to this problem will be found, for better or worse, in the political arena. In seeking these solutions, increasing conflict can be anticipated between those of a conservative bent favoring ''free enterprise and limited government'' and those of a liberal persuasion arguing for ''big government and public ownership'' in areas directly affecting the public welfare. The financial capability in this country to develop new energy resources on a massive scale through the private enterprise system alone is concluded to be, at best, marginal. The delaymore » in developing conservation programs and new energy resources is portrayed as being ultimately dangerous to the very nature of our political system. (67 references) (auth)« less

A new Early Cretaceous eutherian mammal from the Sasayama Group, Hyogo, Japan.

PubMed

Kusuhashi, Nao; Tsutsumi, Yukiyasu; Saegusa, Haruo; Horie, Kenji; Ikeda, Tadahiro; Yokoyama, Kazumi; Shiraishi, Kazuyuki

2013-05-22

We here describe a new Early Cretaceous (early Albian) eutherian mammal, Sasayamamylos kawaii gen. et sp. nov., from the 'Lower Formation' of the Sasayama Group, Hyogo Prefecture, Japan. Sasayamamylos kawaii is characterized by a robust dentary, a distinct angle on the ventral margin of the dentary at the posterior end of the mandibular symphysis, a lower dental formula of 3-4 : 1 : 4 : 3, a robust lower canine, a non-molariform lower ultimate premolar, and a secondarily reduced entoconid on the molars. To date, S. kawaii is the earliest known eutherian mammal possessing only four premolars, which demonstrates that the reduction in the premolar count in eutherians started in the late Early Cretaceous. The occurrence of S. kawaii implies that the relatively rapid diversification of eutherians in the mid-Cretaceous had already started by the early Albian.

Beyond fast food and slow motion: Weighty contributors to the obesity epidemic

PubMed Central

Cizza, G.; Rother, K.I.

2012-01-01

Decreased physical activity and marketing-driven increased consumption of “junk” food, dubbed “The Big Two”, are generally regarded as the most important contributors to the obesity epidemic. However, the full picture contains many more pieces of the puzzle. We address several additional issues and review current clinical developments in obesity research. In spite of dramatic advancements in our understanding of the adipose organ and its endocrine and immune products, the ultimate causes of the obesity epidemic remain elusive. Treatment is plagued by poor adherence to life style modifications, and available pharmacological options are marginally effective, often also associated with major side effects. Surgical treatments, albeit effective in decreasing body weight, are invasive and expensive. Thus, our approaches to finding the causes, improving the existing treatments, and inventing novel therapies must be manifold. PMID:22183119

Venus, Serena, and the inconspicuous consumption of blackness: a commentary on surveillance, race talk, and new racism(s).

PubMed

Douglas, Delia D

2012-01-01

As the U.S. population becomes more racially diverse and different groups move in to previously White-dominated spaces, new techniques of exclusion and marginalization are being employed in an effort to regulate the opportunities and progress available to racialized minority groups. In this article, the author argues that mass media’s preoccupation with the Williams sisters’ “on-court” play and “off-court” activities constitutes a form of surveillance that is used by Whites to identify, observe, and ultimately, limit the range of available representations of Venus and Serena Williams. The author also suggests that this kind of public scrutiny produces racialized images and narratives constitutive of “race talk,” a key manifestation of the new racism(s) characteristic of the politics of this sociohistorical moment.

Beyond fast food and slow motion: weighty contributors to the obesity epidemic.

PubMed

Cizza, G; Rother, K I

2012-02-01

Decreased physical activity and marketing-driven increased consumption of "junk" food, dubbed "The Big Two", are generally regarded as the most important contributors to the obesity epidemic. However, the full picture contains many more pieces of the puzzle. We address several additional issues and review current clinical developments in obesity research. In spite of dramatic advancements in our understanding of the adipose organ and its endocrine and immune products, the ultimate causes of the obesity epidemic remain elusive. Treatment is plagued by poor adherence to life style modifications, and available pharmacological options are marginally effective, often also associated with major side effects. Surgical treatments, albeit effective in decreasing body weight, are invasive and expensive. Thus, our approaches to finding the causes, improving the existing treatments, and inventing novel therapies must be manifold.

[Mechanical behavior of the subchondral bone in the experimentally induced osteoarthritis].

PubMed

Miyanaga, Y

1979-06-01

In order to evaluate the role of the subchondral bone (cancellous bone) in the development and progression of the joint degeneration, osteoarthritis of the knee joint was produced experimentally in the rabbits and viscoelasticity and strength of the subchondral bone from the femoral medial condyle have been investigated along with the pathological, histological study of the joint. The viscoelastic spectrometer and the Instron type testing machine were used. As the first change after operation, osteophyte formation around the joint margin has been observed before the initiation of the degeneration of articular cartilage and there is a possibility that mechanical properties of subchondral bone such as high deformability and low elasticity to the mechanism of osteophyte formation. Subchondral bone softening with marked increase of ultimate strain and phase lag, marked decrease of compressive elastic modulus and ultimate stress precedes or occurs concurrently with the degeneration of the articular cartilage. These facts indicate the relationship between the mechanical properties of the subchondral bone and joint degeneration. Once the joint degeneration starts, degeneration continues progressively while the subchondral bone tends to become brittle. These changes may be considered as a kind of functional adaptation to the damage or denudation of articular cartilage. It is postulated that some architectural changes of the subchondral bone may provide alterations of the mechanical properties. Biomechanical roles of the subchondral bone is suggested as one of the factors in the joint degeneration.

High-Power Diode Laser-Treated 13Cr4Ni Stainless Steel for Hydro Turbines

NASA Astrophysics Data System (ADS)

Mann, B. S.

2014-06-01

The cast martensitic chromium nickel stainless steels such as 13Cr4Ni, 16Cr5Ni, and 17Cr4Ni PH have found wide application in hydro turbines. These steels have adequate corrosion resistance with good mechanical properties because of chromium content of more than 12%. The 13Cr4Ni stainless steel is most widely used among these steels; however, lacks silt, cavitation, and water impingement erosion resistances (SER, CER, and WIER). This article deals with characterizing 13Cr4Ni stainless steel for silt, cavitation, and water impingement erosion; and studying its improved SER, CER, and WIER behavior after high-power diode laser (HPDL) surface treatment. The WIER and CER have improved significantly after laser treatment, whereas there is a marginal improvement in SER. The main reason for improved WIER and CER is due to its increased surface hardness and formation of fine-grained microstructure after HPDL surface treatment. CER and WIER of HPDL-treated 13Cr4Ni stainless steel samples have been evaluated as per ASTM G32-2003 and ASTM G73-1978, respectively; and these were correlated with microstructure and mechanical properties such as ultimate tensile strength, modified ultimate resilience, and microhardness. The erosion damage mechanism, compared on the basis of scanning electron micrographs and mechanical properties, is discussed and reported in this article.

Korean version of the Revised Caregiving Appraisal Scale: a translation and validation study.

PubMed

Lee, JuHee; Friedmann, Erika; Picot, Sandra J; Thomas, Sue Ann; Kim, Cho Ja

2007-08-01

This paper is a report of a study to examine the reliability and validity of a Korean version of the Revised Caregiving Appraisal Scale with Korean caregivers of older stroke survivors. The Revised Caregiving Appraisal Scale was developed in the United States of America for an American English-speaking population to measure primary caregivers' appraisals of potential stressors and the efficacy of their coping efforts related to caregiving experiences. Using the back-translation method, the instrument was translated into Korean. The Korean version of the Revised Caregiving Appraisal Scale was self-administered by 147 primary family caregivers recruited from three outpatient clinics and two home health agencies in Korea. The study was conducted in 2005. In this sample, Cronbach's alpha for the total scale was 0.86. Reliability coefficients for each of the five subscales ranged from 0.40 to 0.85. Two subscales, burden and satisfaction, showed good reliability; one subscale, impact, showed marginally acceptable reliability; two subscales, mastery and demand, had low reliability. Principal components factor analysis of the Korean version of the Revised Caregiving Appraisal Scale yielded six factors. Except for the mastery domain, which was divided into two factors, the other factors were similar to those in the original scale. The Korean version of the Revised Caregiving Appraisal Scale had adequate reliability and validity in a sample of Korean caregivers of stroke survivors. It can be used to assess the impact of caregiving and interventions on Korean caregiver attitudes. Further studies are needed with different categories of caregiver.

Along-strike Translation of a Fossil Slab Beneath California (Invited)

NASA Astrophysics Data System (ADS)

Forsyth, D. W.

2013-12-01

There are three places where subduction ceased before a spreading ridge was consumed at a trench, leaving behind remnant microplates that were incorporated into the non-subducting oceanic plate. In the cases of the Phoenix plate off the Antarctic peninsula and the Guadalupe and Magdalena microplates off Baja California, fossil slabs still attached to the microplates have been traced into the asthenosphere using seismological techniques. Apparently deep subducting plates can tear off from the surface plate leaving behind fossil pieces of young oceanic lithosphere extending 100 km or more into the asthenosphere. The young slab fragments may be close to neutral buoyancy with their asthenospheric surroundings. In the case of the Monterey microplate off central California, now part of the Pacific plate, oceanic crust has been traced beneath the continental margin using active source seismology. Nicholson et al. (1994) suggested that the translation of the Monterey microplate under North America dragged bits of the overriding plate with it, causing the rotation of the Transverse Ranges in southern California. They also suggested that the San Andreas initiated as a low angle fault between the overriding North American plate and the subducted Monterey plate. There is a gap in coastal, post-subduction volcanic activity opposite the microplate, perhaps because a slab window never formed. A steeply dipping seismic anomaly, the Isabella anomaly, also lies opposite the microplate, probably indicating the continuation of the Monterey slab deep into the asthenosphere. Between the Isabella anomaly and the surface remnants of the Monterey microplate lies the aseismic, creeping section of the San Andreas fault, which we speculate may be caused by the migration of fluids from the subducted plate. The Monterey case differs from the Phoenix and Guadalupe cases in that the hypothesized fossil slab lies beneath the North American plate, which is translating relative to the Pacific/Monterey plate. We have shown that the fossil slab could translate with the Monterey plate with reasonable viscosity contrast with the surrounding asthenosphere.

Translational Research on the Way to Effective Therapy for Alzheimer Disease

PubMed Central

Rosenberg, Roger N.

2006-01-01

Context Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. Objective A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. Conclusions A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope. PMID:16275806

Translational research on the way to effective therapy for Alzheimer disease.

PubMed

Rosenberg, Roger N

2005-11-01

Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data. including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope.

Size Constraints on Late Miocene to Pliocene Submarine Slope Failures along the Colombian Caribbean Subduction Margin as a Basis for Assessing Circum-Caribbean Impact of Future Tsunami Events

NASA Astrophysics Data System (ADS)

Leslie, S.; Mann, P.

2015-12-01

The Colombian Caribbean margin provides an ideal setting for the formation of large mass transport deposits (MTDs): 1) the Caribbean Plate is slowly subducting at rates of 20 mm/yr with infrequent large thrust earthquakes and a complete lack of subduction events in the 400-year-long historical record; 2) the margin is a broad zone of active faults including a ~50 km-wide accretionary prism and strike-slip faults landward of the prism; 3) the active margin is draped by the Magdalena delta and submarine fan fed by the Magdalena River, the 26th largest in the world; and 4) the margin is over-steepened to slopes of up to 7° from the combination of tectonic activity and rapid rates of deltaic progradation. Using seismic data we have identified three late Miocene-Pliocene MTDs, the largest of which is between 4500 and 6000 km3, comparable in size to the well-studied Storegga slide of Norway. The tsunamigenic potential of future, analog MTD events are modeled using GeoWave tsunami modeling software. The largest and youngest of these MTDs, the Santa Marta slide, is used as an analog to infer the location and input parameters for the tsunami model. The event is modeled as a translational slide ~46 km long and ~37 km wide with the center of the slide located ~57 km W/NW from the mouth of the present day Magdalena River in water depths of 1500 m. The volume for the initial failure is conservatively estimated at ~680 km3 of material. The resulting tsunami wave from such an event has an initial maximum trough amplitude of -65.8 m and a peak amplitude of 19.2 m. The impact of such a tsunami would include: 1) Kingston, Jamaica (population 938K), tsunami height 7.5 m, peak arrival at 60 min.; 2) Santo Domingo, Dominican Republic (population 965K, height 6 m, peak arrival at 80 min.); and 3) Cartagena, Colombia (population 845K, height 21 m, peak arrival at 34 min.). A number of parameters to the model are varied to analyze sensitivity of modeling results to changes in slide depth, angle of failure, slide volume, and slide density.

Ocean Drilling Program Leg 112, Peru continental margin: Part 2, Sedimentary history and diagenesis in a coastal upwelling environment

NASA Astrophysics Data System (ADS)

Suess, E.; von Huene, R.

1988-10-01

On the shelf and upper slope off Peru the signal of coastal upwelling productivity and bottom-water oxygen is well preserved in alternately laminated and bioturbated diatomaceous Quaternary sediments. Global sea-level fluctuations are the ultimate cause for these cyclic facies changes. During late Miocene time, coastal upwelling was about 100 km west of the present centers, along the edge of an emergent structure that subsequently subsided to form the modern slope. The sediments are rich in organic carbon, and intense microbially mediated decomposition of organic matter is evident in sulfate reduction and methanogenesis. These processes are accompanied by the formation of diagenetic carbonates, mostly Ca-rich dolomites and Mg-calcites. The downhole isotopic signatures of these carbonate cements display distinct successions that reflect the vertical evolution of the pore fluid environment. From the association of methane gas hydrates, burial depth, and low-chloride interstitial fluids, we suggest an additional process that could contribute to the characteristic chloride depletion in pore fluids of active margins: release of interlayer water from clays without a mineral phase change. The shelf sediments also contain a subsurface brine that stretches for more than 500 km from north to south over the area drilled. The source of the brine remains uncertain, although the composition of the oxygen isotopes suggests dissolution of evaporites by seawater.

Ex-vivo holographic microscopy and spectroscopic analysis of head and neck cancer

NASA Astrophysics Data System (ADS)

Holler, Stephen; Wurtz, Robert; Auyeung, Kelsey; Auyeung, Kris; Paspaley-Grbavac, Milan; Mulroe, Brigid; Sobrero, Maximiliano; Miles, Brett

2015-03-01

Optical probes to identify tumor margins in vivo would greatly reduce the time, effort and complexity in the surgical removal of malignant tissue in head and neck cancers. Current approaches involve visual microscopy of stained tissue samples to determine cancer margins, which results in the excision of excess of tissue to assure complete removal of the cancer. Such surgical procedures and follow-on chemotherapy can adversely affect the patient's recovery and subsequent quality of life. In order to reduce the complexity of the process and minimize adverse effects on the patient, we investigate ex vivo tissue samples (stained and unstained) using digital holographic microscopy in conjunction with spectroscopic analyses (reflectance and transmission spectroscopy) in order to determine label-free, optically identifiable characteristic features that may ultimately be used for in vivo processing of cancerous tissues. The tissue samples studied were squamous cell carcinomas and associated controls from patients of varying age, gender and race. Holographic microscopic imaging scans across both cancerous and non-cancerous tissue samples yielded amplitude and phase reconstructions that were correlated with spectral signatures. Though the holographic reconstructions and measured spectra indicate variations even among the same class of tissue, preliminary results indicate the existence of some discriminating features. Further analyses are presently underway to further this work and extract additional information from the imaging and spectral data that may prove useful for in vivo surgical identification.

The STAT7 Code for Statistical Propagation of Uncertainties In Steady-State Thermal Hydraulics Analysis of Plate-Fueled Reactors

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

Dunn, Floyd E.; Hu, Lin-wen; Wilson, Erik

The STAT code was written to automate many of the steady-state thermal hydraulic safety calculations for the MIT research reactor, both for conversion of the reactor from high enrichment uranium fuel to low enrichment uranium fuel and for future fuel re-loads after the conversion. A Monte-Carlo statistical propagation approach is used to treat uncertainties in important parameters in the analysis. These safety calculations are ultimately intended to protect against high fuel plate temperatures due to critical heat flux or departure from nucleate boiling or onset of flow instability; but additional margin is obtained by basing the limiting safety settings onmore » avoiding onset of nucleate boiling. STAT7 can simultaneously analyze all of the axial nodes of all of the fuel plates and all of the coolant channels for one stripe of a fuel element. The stripes run the length of the fuel, from the bottom to the top. Power splits are calculated for each axial node of each plate to determine how much of the power goes out each face of the plate. By running STAT7 multiple times, full core analysis has been performed by analyzing the margin to ONB for each axial node of each stripe of each plate of each element in the core.« less

Predicting health care utilization in marginalized populations: Black, female, street-based sex workers.

PubMed

Varga, Leah M; Surratt, Hilary L

2014-01-01

Patterns of social and structural factors experienced by vulnerable populations may negatively affect willingness and ability to seek out health care services, and ultimately, their health. The outcome variable was utilization of health care services in the previous 12 months. Using Andersen's Behavioral Model for Vulnerable Populations, we examined self-reported data on utilization of health care services among a sample of 546 Black, street-based, female sex workers in Miami, Florida. To evaluate the impact of each domain of the model on predicting health care utilization, domains were included in the logistic regression analysis by blocks using the traditional variables first and then adding the vulnerable domain variables. The most consistent variables predicting health care utilization were having a regular source of care and self-rated health. The model that included only enabling variables was the most efficient model in predicting health care utilization. Any type of resource, link, or connection to or with an institution, or any consistent point of care, contributes significantly to health care utilization behaviors. A consistent and reliable source for health care may increase health care utilization and subsequently decrease health disparities among vulnerable and marginalized populations, as well as contribute to public health efforts that encourage preventive health. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

PubMed Central

Steinman, Lawrence

2016-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Lawrence Steinman, MD, of Stanford University in California. A visionary in the field of neurology, this is the story of Dr. Steinman’s scientific journey. PMID:27652378

Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics.

PubMed

Mailloux, Ryan J; McBride, Skye L; Harper, Mary-Ellen

2013-12-01

During the cellular oxidation of fuels, electrons are used to power the proton pumps of the mitochondrial electron transport chain (ETC) and ultimately drive ATP synthesis and the reduction of molecular oxygen to water. During these oxidative processes, some electrons can 'spin off' during fuel oxidation and electron transport to univalently reduce O2, forming reactive oxygen species (ROS). In excess, ROS can be detrimental; however, at low concentrations oxyradicals are essential signaling molecules. Mitochondria thus use a battery of systems to finely control types and levels of ROS, including antioxidants. Several antioxidant systems depend on glutathione. Here, we review mitochondrial ROS homeostatic systems, including emerging knowledge about roles of glutathione in redox balance and the control of protein function by post-translational modification. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relating Human Genetic Variation to Variation in Drug Responses

PubMed Central

Madian, Ashraf G.; Wheeler, Heather E.; Jones, Richard Baker; Dolan, M. Eileen

2012-01-01

Although sequencing a single human genome was a monumental effort a decade ago, more than one thousand genomes have now been sequenced. The task ahead lies in transforming this information into personalized treatment strategies that are tailored to the unique genetics of each individual. One important aspect of personalized medicine is patient-to-patient variation in drug response. Pharmacogenomics addresses this issue by seeking to identify genetic contributors to human variation in drug efficacy and toxicity. Here, we present a summary of the current status of this field, which has evolved from studies of single candidate genes to comprehensive genome-wide analyses. Additionally, we discuss the major challenges in translating this knowledge into a systems-level understanding of drug physiology with the ultimate goal of developing more effective personalized clinical treatment strategies. PMID:22840197

Precision medicine in chronic disease management: the MS BioScreen

PubMed Central

Gourraud, Pierre-Antoine; Henry, Roland; Cree, Bruce AC; Crane, Jason C; Lizee, Antoine; Olson, Marram P; Santaniello, Adam V.; Datta, Esha; Zhu, Alyssa H.; Bevan, Carolyn J.; Gelfand, Jeffrey M.; Graves, Jennifer A.; Goodin, Douglas E.; Green, Ari; von Büdingen, H.-Christian; Waubant, Emmanuelle; Zamvil, Scott S.; Crabtree-Hartman, Elizabeth; Nelson, Sarah; Baranzini, Sergio E.; Hauser, Stephen L.

2014-01-01

We present a precision medicine application developed for multiple sclerosis (MS): the MS BioScreen. This new tool addresses the challenges of dynamic management of a complex chronic disease; the interaction of clinicians and patients with such a tool illustrates the extent to which translational digital medicine – i.e. the application of information technology to medicine—has the potential to radically transform medical practice. We introduce three key evolutionary phases in displaying data to health care providers, patients, and researchers: visualization (accessing data), contextualization (understanding the data), and actionable interpretation (real-time use of the data to assist decision-making). Together these form the stepping-stones that are expected to accelerate standardization of data across platforms, promote evidence-based medicine, support shared decision-making, and ultimately lead to improved outcomes. PMID:25263997

Big Numbers about Small Children: Estimating the Economic Benefits of Addressing Undernutrition.

PubMed

Alderman, Harold; Behrman, Jere R; Puett, Chloe

2017-02-01

Different approaches have been used to estimate the economic benefits of reducing undernutrition and to estimate the costs of investing in such programs on a global scale. While many of these studies are ultimately based on evidence from well-designed efficacy trials, all require a number of assumptions to project the impact of such trials to larger populations and to translate the value of the expected improvement in nutritional status into economic terms. This paper provides a short critique of some approaches to estimating the benefits of investments in child nutrition and then presents an alternative set of estimates based on different core data. These new estimates reinforce the basic conclusions of the existing literature: the economic value from reducing undernutrition in undernourished populations is likely to be substantial.

Targeting women or transforming institutions? Policy lessons from NGO anti-poverty efforts.

PubMed

Kabeer, N

1995-05-01

Some research has found that the extent of gender-based discrimination in market-based institutions and unfair advantages within domestic and market institutions meant women were less successful in translating education and work into income and purchasing power. Anti-poverty programs functioned without specifically addressing the implications for women and children. Women-in-development efforts attempted to compensate for prior deficiencies by promotion of income generation schemes for women. In this article, the suggestion is made for policy makers to design projects with goals, objectives, and strategies that are clear, consistent, and well-informed about gender. Efforts should be made to avoid debates about women-only versus integrated projects. The experiences of nongovernmental organizations (NGOs) in the South Asian context offer lessons in good policy efforts to address all forms of marginalization. The definition of women's needs must be provided by women themselves; openness and flexibility are recommended. Participatory approaches serve the aims of needs identification, involvement in democratic processes, and awareness of constraints on women's use of resources. In credit lending, constraints were overcome by compensating for the absence of material collateral, guaranteeing physical access, simplifying procedures, and subsidizing access rather than interest rates. Underlying structural conditions that reinforce inequalities by gender are in need of change. Empowerment of women would assure that marginalization would not occur.

Helical tomotherapy setup variations in canine nasal tumor patients immobilized with a bite block.

PubMed

Kubicek, Lyndsay N; Seo, Songwon; Chappell, Richard J; Jeraj, Robert; Forrest, Lisa J

2012-01-01

The purpose of our study was to compare setup variation in four degrees of freedom (vertical, longitudinal, lateral, and roll) between canine nasal tumor patients immobilized with a mattress and bite block, versus a mattress alone. Our secondary aim was to define a clinical target volume (CTV) to planning target volume (PTV) expansion margin based on our mean systematic error values associated with nasal tumor patients immobilized by a mattress and bite block. We evaluated six parameters for setup corrections: systematic error, random error, patient-patient variation in systematic errors, the magnitude of patient-specific random errors (root mean square [RMS]), distance error, and the variation of setup corrections from zero shift. The variations in all parameters were statistically smaller in the group immobilized by a mattress and bite block. The mean setup corrections in the mattress and bite block group ranged from 0.91 mm to 1.59 mm for the translational errors and 0.5°. Although most veterinary radiation facilities do not have access to Image-guided radiotherapy (IGRT), we identified a need for more rigid fixation, established the value of adding IGRT to veterinary radiation therapy, and define the CTV-PTV setup error margin for canine nasal tumor patients immobilized in a mattress and bite block. © 2012 Veterinary Radiology & Ultrasound.

Viral activities and life cycles in deep subseafloor sediments.

PubMed

Engelhardt, Tim; Orsi, William D; Jørgensen, Bo Barker

2015-12-01

Viruses are highly abundant in marine subsurface sediments and can even exceed the number of prokaryotes. However, their activity and quantitative impact on microbial populations are still poorly understood. Here, we use gene expression data from published continental margin subseafloor metatranscriptomes to qualitatively assess viral diversity and activity in sediments up to 159 metres below seafloor (mbsf). Mining of the metatranscriptomic data revealed 4651 representative viral homologues (RVHs), representing 2.2% of all metatranscriptome sequence reads, which have close translated homology (average 77%, range 60-97% amino acid identity) to viral proteins. Archaea-infecting RVHs are exclusively detected in the upper 30 mbsf, whereas RVHs for filamentous inoviruses predominate in the deepest sediment layers. RVHs indicative of lysogenic phage-host interactions and lytic activity, notably cell lysis, are detected at all analysed depths and suggest a dynamic virus-host association in the marine deep biosphere studied here. Ongoing lytic viral activity is further indicated by the expression of clustered, regularly interspaced, short palindromic repeat-associated cascade genes involved in cellular defence against viral attacks. The data indicate the activity of viruses in subsurface sediment of the Peruvian margin and suggest that viruses indeed cause cell mortality and may play an important role in the turnover of subseafloor microbial biomass. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Hydrochemical and 14C constraints on groundwater recharge and interbasin flow in an arid watershed: Tule Desert, Nevada

NASA Astrophysics Data System (ADS)

Hagedorn, Benjamin

2015-04-01

Geochemical data deduced from groundwater and vein calcite were used to quantify groundwater recharge and interbasin flow rates in the Tule Desert (southeastern Nevada). 14C age gradients below the water table suggest recharge rates of 1-2 mm/yr which correspond to a sustainable yield of 5 × 10-4 km3/yr to 1 × 10-3 km3/yr. Uncertainties in the applied effective porosity value and increasing horizontal interbasin flow components at greater depths may bias these estimates low compared to those previously reported using the water budget method. The deviation of the groundwater δ18O time-series pattern for the Pleistocene-Holocene transition from that of the Devils Hole vein calcite (which is considered a proxy for local climate change) allows interbasin flow rates of northerly derived groundwater to be estimated. The constrained rates (75.0-120 m/yr) are slightly higher than those previously calculated using Darcy's Law, but translate into hydraulic conductivity values strikingly similar to those obtained from pump tests. Data further indicate that production wells located closer to the western mountainous margin will be producing mainly from locally derived mountain-system recharge whereas wells located closer to the eastern margin are more influenced by older, regionally derived carbonate groundwater.

Translating hydrologically-relevant variables from the ice sheet model SICOPOLIS to the Greenland Analog Project hydrologic modeling domain

NASA Astrophysics Data System (ADS)

Vallot, Dorothée; Applegate, Patrick; Pettersson, Rickard

2013-04-01

Projecting future climate and ice sheet development requires sophisticated models and extensive field observations. Given the present state of our knowledge, it is very difficult to say what will happen with certainty. Despite the ongoing increase in atmospheric greenhouse gas concentrations, the possibility that a new ice sheet might form over Scandinavia in the far distant future cannot be excluded. The growth of a new Scandinavian Ice Sheet would have important consequences for buried nuclear waste repositories. The Greenland Analogue Project, initiated by the Swedish Nuclear Fuel and Waste Management Company (SKB), is working to assess the effects of a possible future ice sheet on groundwater flow by studying a constrained domain in Western Greenland by field measurements (including deep bedrock drilling in front of the ice sheet) combined with numerical modeling. To address the needs of the GAP project, we interpolated results from an ensemble of ice sheet model runs to the smaller and more finely resolved modeling domain used in the GAP project's hydrologic modeling. Three runs have been chosen with three fairly different positive degree-day factors among those that reproduced the modern ice margin at the borehole position. The interpolated results describe changes in hydrologically-relevant variables over two time periods, 115 ka to 80 ka, and 20 ka to 1 ka. In the first of these time periods, the ice margin advances over the model domain; in the second time period, the ice margin retreats over the model domain. The spatially-and temporally dependent variables that we treated include the ice thickness, basal melting rate, surface mass balance, basal temperature, basal thermal regime (frozen or thawed), surface temperature, and basal water pressure. The melt flux is also calculated.

Geologic Assessment of Undiscovered Oil and Gas Resources of the North Cuba Basin, Cuba

USGS Publications Warehouse

Schenk, Christopher J.

2010-01-01

Petroleum generation in the North Cuba Basin is primarily the result of thrust loading of Jurassic and Cretaceous source rocks during formation of the North Cuba fold and thrust belt in the Late Cretaceous to Paleogene. The fold and thrust belt formed as Cuban arc-forearc rocks along the leading edge of the Caribbean plate translated northward during the opening of the Yucatan Basin and collided with the passive margin of southern North America in the Paleogene. Petroleum fluids generated during thrust loading migrated vertically into complex structures in the fold and thrust belt, into structures in the foreland basin, and possibly into carbonate reservoirs along the margins of the Yucatan and Bahama carbonate platforms. The U.S. Geological Survey (USGS) defined a Jurassic-Cretaceous Composite Total Petroleum System (TPS) and three assessment units (AU)-North Cuba Fold and Thrust Belt AU, North Cuba Foreland Basin AU, and the North Cuba Platform Margin Carbonate AU-within this TPS based mainly on structure and reservoir type (fig. 1). There is considerable geologic uncertainty as to the extent of petroleum migration that might have occurred within this TPS to form potential petroleum accumulations. Taking this geologic uncertainty into account, especially in the offshore area, the mean volumes of undiscovered resources in the composite TPS of the North Cuba Basin are estimated at (1) 4.6 billion barrels of oil (BBO), with means ranging from an F95 probability of 1 BBO to an F5 probability of 9 BBO; and (2) 8.6 trillion cubic feet of of gas (TCFG), of which 8.6 TCFG is associated with oil fields, and about 1.2 TCFG is in nonassociated gas fields in the North Cuba Foreland Basin AU.

Monte Carlo simulation to analyze the cost-benefit of radioactive seed localization versus wire localization for breast-conserving surgery in fee-for-service health care systems compared with accountable care organizations.

PubMed

Loving, Vilert A; Edwards, David B; Roche, Kevin T; Steele, Joseph R; Sapareto, Stephen A; Byrum, Stephanie C; Schomer, Donald F

2014-06-01

In breast-conserving surgery for nonpalpable breast cancers, surgical reexcision rates are lower with radioactive seed localization (RSL) than wire localization. We evaluated the cost-benefit of switching from wire localization to RSL in two competing payment systems: a fee-for-service (FFS) system and a bundled payment system, which is typical for accountable care organizations. A Monte Carlo simulation was developed to compare the cost-benefit of RSL and wire localization. Equipment utilization, procedural workflows, and regulatory overhead differentiate the cost between RSL and wire localization. To define a distribution of possible cost scenarios, the simulation randomly varied cost drivers within fixed ranges determined by hospital data, published literature, and expert input. Each scenario was replicated 1000 times using the pseudorandom number generator within Microsoft Excel, and results were analyzed for convergence. In a bundled payment system, RSL reduced total health care cost per patient relative to wire localization by an average of $115, translating into increased facility margin. In an FFS system, RSL reduced total health care cost per patient relative to wire localization by an average of $595 but resulted in decreased facility margin because of fewer surgeries. In a bundled payment system, RSL results in a modest reduction of cost per patient over wire localization and slightly increased margin. A fee-for-service system suffers moderate loss of revenue per patient with RSL, largely due to lower reexcision rates. The fee-for-service system creates a significant financial disincentive for providers to use RSL, although it improves clinical outcomes and reduces total health care costs.

Chronic kidney disease guideline implementation in primary care: a qualitative report from the TRANSLATE CKD study

PubMed Central

Vest, Bonnie M.; York, Trevor R.M.; Sand, Jessica; Fox, Chester H.; Kahn, Linda S.

2016-01-01

Background Primary care physicians (PCPs) are optimally situated to identify and manage early-stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national mixed-methods cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. Methods As part of mixed-methods process evaluation, semi-structured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the four domains of Normalization Process Theory (NPT). Results Identified themes illuminated the complex work undertaken in primary care practices to manage CKD. Barriers to guideline implementation were identified in each of the four NPT domains, including: 1) lack of knowledge and understanding around CKD (coherence), 2) difficulties engaging providers and patients in CKD management (cognitive participation), 3) limited time and competing demands (collective action), and 4) challenges obtaining and utilizing data to monitor progress (reflexive monitoring). Conclusions Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. PMID:26355134

Hospital-Based Comparative Effectiveness Centers: Translating Research into Practice to Improve the Quality, Safety and Value of Patient Care

PubMed Central

Williams, Kendal; Brennan, Patrick J.

2010-01-01

Hospital-based comparative effectiveness (CE) centers provide a model that clinical leaders can use to improve evidence-based practice locally. The model is used by integrated health systems outside the US, but is less recognized in the US. Such centers can identify and adapt national evidence-based policies for the local setting, create local evidence-based policies in the absence of national policies, and implement evidence into practice through health information technology (HIT) and quality initiatives. Given the increasing availability of CE evidence and incentives to meaningfully use HIT, the relevance of this model to US practitioners is increasing. This is especially true in the context of healthcare reform, which will likely reduce reimbursements for care deemed unnecessary by published evidence or guidelines. There are challenges to operating hospital-based CE centers, but many of these challenges can be overcome using solutions developed by those currently leading such centers. In conclusion, these centers have the potential to improve the quality, safety and value of care locally, ultimately translating into higher quality and more cost-effective care nationally. To better understand this potential, the current activity and impact of hospital-based CE centers in the US should be rigorously examined. PMID:20697961

Evolutionary Consequence of a Trade-Off between Growth and Maintenance along with Ribosomal Damages.

PubMed

Ying, Bei-Wen; Honda, Tomoya; Tsuru, Saburo; Seno, Shigeto; Matsuda, Hideo; Kazuta, Yasuaki; Yomo, Tetsuya

2015-01-01

Microorganisms in nature are constantly subjected to a limited availability of resources and experience repeated starvation and nutrition. Therefore, microbial life may evolve for both growth fitness and sustainability. By contrast, experimental evolution, as a powerful approach to investigate microbial evolutionary strategies, often targets the increased growth fitness in controlled, steady-state conditions. Here, we address evolutionary changes balanced between growth and maintenance while taking nutritional fluctuations into account. We performed a 290-day-long evolution experiment with a histidine-requiring Escherichia coli strain that encountered repeated histidine-rich and histidine-starved conditions. The cells that experienced seven rounds of starvation and re-feed grew more sustainably under prolonged starvation but dramatically lost growth fitness under rich conditions. The improved sustainability arose from the evolved capability to use a trace amount of histidine for cell propagation. The reduced growth rate was attributed to mutations genetically disturbing the translation machinery, that is, the ribosome, ultimately slowing protein translation. This study provides the experimental demonstration of slow growth accompanied by an enhanced affinity to resources as an evolutionary adaptation to oscillated environments and verifies that it is possible to evolve for reduced growth fitness. Growth economics favored for population increase under extreme resource limitations is most likely a common survival strategy adopted by natural microbes.

What research ethics should learn from genomics and society research: lessons from the ELSI Congress of 2011.

PubMed

Henderson, Gail E; Juengst, Eric T; King, Nancy M P; Kuczynski, Kristine; Michie, Marsha

2012-01-01

Research on the ethical, legal, and social implications (ELSI) of human genomics has devoted significant attention to the research ethics issues that arise from genomic science as it moves through the translational process. Given the prominence of these issues in today's debates over the state of research ethics overall, these studies are well positioned to contribute important data, contextual considerations, and policy arguments to the wider research ethics community's deliberations, and ultimately to develop a research ethics that can help guide biomedicine's future. In this essay, we illustrate this thesis through an analytic summary of the research presented at the 2011 ELSI Congress, an international meeting of genomics and society researchers. We identify three pivotal factors currently shaping genomic research, its clinical translation, and its societal implications: (1) the increasingly blurred boundary between research and treatment; (2) uncertainty--that is, the indefinite, indeterminate, and incomplete nature of much genomic information and the challenges that arise from making meaning and use of it; and (3) the role of negotiations between multiple scientific and non-scientific stakeholders in setting the priorities for and direction of biomedical research, as it is increasingly conducted "in the public square." © 2012 American Society of Law, Medicine & Ethics, Inc.

Recommendations for the Definition of Clinical Responder in Insulin Preservation Studies

PubMed Central

Gitelman, Stephen E.; Palmer, Jerry P.

2014-01-01

Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials prespecify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In this article, we propose a clinical responder definition to specifically assist researchers and regulatory agencies in interpreting the clinical importance of statistically significant findings for studies of interventions intended to preserve β-cell function in newly diagnosed type 1 diabetes. We focus on studies of 6-month β-cell preservation in type 1 diabetes as measured by 2-h–stimulated C-peptide. We introduce criteria (bias, reliability, and external validity) for the assessment of responder definitions to ensure they meet U.S. Food and Drug Administration and European Medicines Agency guidelines. Using data from several published TrialNet studies, we evaluate our definition (no decrease in C-peptide) against published alternatives and determine that our definition has minimum bias with external validity. We observe that reliability could be improved by using changes in C-peptide later than 6 months beyond baseline. In sum, to support efficacy claims of β-cell preservation therapies in type 1 diabetes submitted to U.S. and European regulatory agencies, we recommend use of our definition. PMID:24722251

Translating Current Science into Materials for High School via a Scientist-Teacher Partnership

NASA Astrophysics Data System (ADS)

Brown, Julie C.; Bokor, Julie R.; Crippen, Kent J.; Koroly, Mary Jo

2014-04-01

Scientist-teacher partnerships are a unique form of professional development that can assist teachers in translating current science into classroom instruction by involving them in meaningful collaborations with university researchers. However, few reported models aim to directly alter science teachers' practices by supporting them in the development of curriculum materials. This article reports on a multiple case study of seven high school science teachers who attended an ongoing scientist-teacher partnership professional development program at a major Southeastern research university. Our interest was to understand the capacity of this professional development program for supporting teachers in the transfer of personal learning experiences with advanced science content and skills into curriculum materials for high school students. Findings indicate that, regardless of their ultimate success constructing curriculum materials, all cases considered the research grounded professional development supports beneficial to their professional growth with the exception of collective participation. Additionally, the cases also described how supports such as professional recognition and transferability served as affordances to the process of constructing these materials. However, teachers identified multiple constraints, including personal learning barriers, their classroom context, and the cost associated with implementing some of their curriculum ideas. Results have direct implications for future research and the purposeful design of professional development experiences through scientist-teacher partnerships.

Chronic Kidney Disease Guideline Implementation in Primary Care: A Qualitative Report from the TRANSLATE CKD Study.

PubMed

Vest, Bonnie M; York, Trevor R M; Sand, Jessica; Fox, Chester H; Kahn, Linda S

2015-01-01

Primary care physicians (PCPs) are optimally situated to identify and manage early stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national, mixed-methods, cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. As part of the mixed-methods process evaluation, semistructured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the 4 domains of Normalization Process Theory (NPT). Identified themes illuminated the complex work undertaken to manage CKD in primary care practices. Barriers to guideline implementation were identified in each of the 4 NPT domains, including (1) lack of knowledge and understanding around CKD (coherence), (2) difficulties engaging providers and patients in CKD management (cognitive participation), (3) limited time and competing demands (collective action), and (4) challenges obtaining and using data to monitor progress (reflexive monitoring). Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. © Copyright 2015 by the American Board of Family Medicine.

From research to evidence-informed decision making: a systematic approach

PubMed Central

Poot, Charlotte C; van der Kleij, Rianne M; Brakema, Evelyn A; Vermond, Debbie; Williams, Siân; Cragg, Liza; van den Broek, Jos M; Chavannes, Niels H

2018-01-01

Abstract Background Knowledge creation forms an integral part of the knowledge-to-action framework aimed at bridging the gap between research and evidence-informed decision making. Although principles of science communication, data visualisation and user-centred design largely impact the effectiveness of communication, their role in knowledge creation is still limited. Hence, this article aims to provide researchers a systematic approach on how knowledge creation can be put into practice. Methods A systematic two-phased approach towards knowledge creation was formulated and executed. First, during a preparation phase the purpose and audience of the knowledge were defined. Subsequently, a developmental phase facilitated how the content is ‘said’ (language) and communicated (channel). This developmental phase proceeded via two pathways: a translational cycle and design cycle, during which core translational and design components were incorporated. The entire approach was demonstrated by a case study. Results The case study demonstrated how the phases in this systematic approach can be operationalised. It furthermore illustrated how created knowledge can be delivered. Conclusion The proposed approach offers researchers a systematic, practical and easy-to-implement tool to facilitate effective knowledge creation towards decision-makers in healthcare. Through the integration of core components of knowledge creation evidence-informed decision making will ultimately be optimized. PMID:29538728

Detailed analysis of the Valdes slide: a landward facing slope failure off Chile

NASA Astrophysics Data System (ADS)

Anasetti, Andrea; Krastel, Sebastian; Weinrebe, Willy; Klaucke, Ingo; Bialas, Jorge

2010-05-01

The Chilean continental margin is a very active area interested by important tectonic movements and characterized by a fast morphological evolution. Geophysical data acquired during cruise JC 23, aboard RV JAMES COOK in March/April 2008 and previous cruises cover most of the active Chilean continental margin between 33° and 37° S. Integrated interpretation of multi-beam bathymetric, sub-bottom profiles, side-scan sonar and seismic data allowed the identification of a number of slope failures. The main topic of this project is the morphological and sedimentological analysis of the Valdes slide, a medium-sized submarine landslide offshore the city of Talcahuano (300 km south of Santiago). In contrast to most other slides along continental margins, the Valdes slide is located on the landward facing eastern slope of a submarine ridge. This setting has important implications for the associated tsunami wave field (first arrival of positive amplitude). We measured geometrical parameters of the failure and adjacent slope. The slide affected an area of 19 km2 between ~1060 m and >1700 m water depths. Its is ~ 6 km long, up to 3 km wide and involved a total sedimentary volume of about 0,8 km3. The failure process was characterized by a multiple-event and we assume its tsunami potential to be high. Using the high resolution bathymetric data and the seismic profiles along the slide deposit it was possible to reconstruct the original morphology of the area in order to understand the relation between the slide event and the structural evolution of the ridge. Through the analysis of the data and bibliographic information about the Chilean margin, we analyzed potential trigger mechanisms for the landslide. The Valdes slide is situated on a steep ridge flank. The ridge follows an elongated fault zone running app. parallel to the margin. This fault zone has a dextral component which in combination with the faults elongation results in a compressional regime that is superimposed on the overall subduction-related compression and ultimately generated this ridge. Over-steepening (slope angle >6° ) of rapidly accumulated sediments (high sedimentation rate) and the huge uplift of the ridge seem to be the most important preconditioning factors of this slide. Seismic data and core analysis suggest that a weak layer acted as sliding surface. The most likely trigger can be assumed one of the frequently occurring strong earthquakes in this area.

Modified suture-bridge technique to prevent a marginal dog-ear deformity improves structural integrity after rotator cuff repair.

PubMed

Ryu, Keun Jung; Kim, Bang Hyun; Lee, Yohan; Lee, Yoon Seok; Kim, Jae Hwa

2015-03-01

The arthroscopic suture-bridge technique has proved to provide biomechanically firm fixation of the torn rotator cuff to the tuberosity by increasing the footprint contact area and pressure. However, a marginal dog-ear deformity is encountered not infrequently when this technique is used, impeding full restoration of the torn cuff. To evaluate the structural and functional outcomes of the use of a modified suture-bridge technique to prevent a marginal dog-ear deformity compared with a conventional suture-bridge method in rotator cuff repair. Cohort study; Level of evidence 2. A consecutive series of 71 patients aged 50 to 65 years who underwent arthroscopic rotator cuff repair for full-thickness medium-sized to massive tears was evaluated. Patients were divided into 2 groups according to repair technique: a conventional suture-bridge technique (34 patients; group A) versus a modified suture-bridge technique to prevent a marginal dog-ear deformity (37 patients; group B). Radiographic evaluations included postoperative cuff integrity using MRI. Functional evaluations included pre- and postoperative range of motion (ROM), pain visual analog scale (VAS), the University of California, Los Angeles (UCLA) shoulder rating scale, the Constant score, and the American Shoulder and Elbow Surgeons (ASES) score. All patients were followed up clinically at a minimum of 1 year. When the 2 surgical techniques were compared, postoperative structural integrity by Sugaya classification showed the distribution of types I:II:III:IV:V to be 4:20:2:4:4 in group A and 20:12:4:0:1 in group B. More subjects in group B had a favorable Sugaya type compared with group A (P < .001). The postoperative healed:retear rate was 26:8 in group A and 36:1 in group B, with a significantly lower retear rate in group B (P = .011). However, there were no significant differences in ROM and all functional outcome scores between the 2 groups postoperatively. When surgical techniques were compared across healed (n = 62) and retear (n = 9) groups, significantly fewer modified suture-bridge technique repairs were found in the retear group (P = .03). There were significant differences between healed and retear groups in functional outcome scores, with worse results in the retear group. A modified suture-bridge technique to prevent a marginal dog-ear deformity provided better structural outcomes than a conventional suture-bridge technique for medium-sized to massive rotator cuff tears. This technique may ultimately provide better functional outcomes by decreasing the retear rate. © 2014 The Author(s).

Modeling menopause: The utility of rodents in translational behavioral endocrinology research.

PubMed

Koebele, Stephanie V; Bimonte-Nelson, Heather A

2016-05-01

The human menopause transition and aging are each associated with an increase in a variety of health risk factors including, but not limited to, cardiovascular disease, osteoporosis, cancer, diabetes, stroke, sexual dysfunction, affective disorders, sleep disturbances, and cognitive decline. It is challenging to systematically evaluate the biological underpinnings associated with the menopause transition in the human population. For this reason, rodent models have been invaluable tools for studying the impact of gonadal hormone fluctuations and eventual decline on a variety of body systems. While it is essential to keep in mind that some of the mechanisms associated with aging and the transition into a reproductively senescent state can differ when translating from one species to another, animal models provide researchers with opportunities to gain a fundamental understanding of the key elements underlying reproduction and aging processes, paving the way to explore novel pathways for intervention associated with known health risks. Here, we discuss the utility of several rodent models used in the laboratory for translational menopause research, examining the benefits and drawbacks in helping us to better understand aging and the menopause transition in women. The rodent models discussed are ovary-intact, ovariectomy, and 4-vinylcylohexene diepoxide for the menopause transition. We then describe how these models may be implemented in the laboratory, particularly in the context of cognition. Ultimately, we aim to use these animal models to elucidate novel perspectives and interventions for maintaining a high quality of life in women, and to potentially prevent or postpone the onset of negative health consequences associated with these significant life changes during aging. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A New Framework and Practice Center for Adapting, Translating, and Scaling Evidence-Based Health/Wellness Programs for People With Disabilities.

PubMed

Rimmer, James H; Vanderbom, Kerri A; Graham, Ian D

2016-04-01

Supporting the transition of people with newly acquired and existing disability from rehabilitation into community-based health/wellness programs, services, and venues requires rehabilitation professionals to build evidence by capturing successful strategies at the local level, finding innovative ways to translate successful practices to other communities, and ultimately to upgrade and maintain their applicability and currency for future scale-up. This article describes a knowledge-to-practice framework housed in a national resource and practice center that will support therapists and other rehabilitation professionals in building and maintaining a database of successful health/wellness guidelines, recommendations, and adaptations to promote community health inclusion for people with disabilities. A framework was developed in the National Center on Health, Physical Activity and Disability (NCHPAD) to systematically build and advance the evidence base of health/wellness programs, practices, and services applicable to people with disabilities. N-KATS (NCHPAD Knowledge Adaptation, Translation, and Scale-up) has 4 sequencing strategies: strategy 1-new evidence- and practice-based knowledge is collected and adapted for the local context (ie, community); strategy 2-customized resources are effectively disseminated to key stakeholders including rehabilitation professionals with appropriate training tools; strategy 3-NCHPAD staff serve as facilitators assisting key stakeholders in implementing recommendations; strategy 4-successful elements of practice (eg, guideline, recommendation, adaptation) are archived and scaled to other rehabilitation providers. The N-KATS framework supports the role of rehabilitation professionals as knowledge brokers, facilitators, and users in a collaborative, dynamic structure that will grow and be sustained over time through the NCHPAD.Video abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A130).

Creating a Knowledge Translation Platform: nine lessons from the Zambia Forum for Health Research.

PubMed

Kasonde, Joseph M; Campbell, Sandy

2012-10-03

The concept of the Knowledge Translation Platform (KTP) provides cohesion and leadership for national-level knowledge translation efforts. In this review, we discuss nine key lessons documenting the experience of the Zambia Forum for Health Research, primarily to inform and exchange experience with the growing community of African KTPs. Lessons from ZAMFOHR's organizational development include the necessity of selecting a multi-stakeholder and -sectoral Board of Directors; performing comprehensive situation analyses to understand not only the prevailing research-and-policy dynamics but a precise operational niche; and selecting a leader that bridges the worlds of research and policy. Programmatic lessons include focusing on building the capacity of both policy-makers and researchers; building a database of local evidence and national-level actors involved in research and policy; and catalyzing work in particular issue areas by identifying leaders from the research community, creating policy-maker demand for research evidence, and fostering the next generation by mentoring both up-and-coming researchers and policy-makers. Ultimately, ZAMFOHR's experience shows that an African KTP must pay significant attention to its organizational details. A KTP must also invest in the skill base of the wider community and, more importantly, of its own staff. Given the very real deficit of research-support skills in most low-income countries - in synthesis, in communications, in brokering, in training - a KTP must spend significant time and resources in building these types of in-house expertise. And lastly, the role of networking cannot be underestimated. As a fully-networked KTP, ZAMFOHR has benefited from the innovations of other KTPs, from funding opportunities and partnerships, and from invaluable technical support from both African and northern colleagues.

Translational cognitive endocrinology: Designing rodent experiments with the goal to ultimately enhance cognitive health in women

PubMed Central

Mennenga, S.E.; Bimonte-Nelson, H.A.

2014-01-01

Understanding the cognitive impact of endogenously derived, and exogenously administered, hormone alterations is necessary for developing hormone treatments to support healthy brain function in women, especially during aging. The increasing number of studies in the burgeoning area of translational cognitive neuroendocrinology has revealed numerous factors that influence the extent and direction of female steroid effects on cognition. Here, we discuss the decision processes underlying the design of rodent hormone manipulation experiments evaluating learning and memory. It is noted that even when beginning with a clear hypothesis-driven question, there are numerous factors to consider in order to solidify a sound experimental design that will yield clean, interpretable results. Decisions and considerations include: age of animals at hormone administration and test, ovariectomy implementation, when to administer hormones relative to ovarian hormone loss, how and whether to monitor the estrous cycle if animals are ovary-intact, dose of hormone, administration route of hormone, hormone treatment confirmation protocols, handling procedures required for hormone administration and treatment confirmation, cognitive domains to be tested and which mazes should be utilized to test these cognitive domains, and control measures to be used. A balanced view of optimal design and realistic experimental practice and protocol is presented. The emerging results from translational cognitive neuroendocrinology studies have been diverse, but also enlightening and exciting as we realize the broad scope and powerful nature of ovarian hormone effects on the brain and its function. We must design, implement, and interpret hormone and cognition experiments with sensitivity to these tenets, acknowledging and respecting the breadth and depth of the impact gonadal hormones have on brain functioning and its rich plasticity. PMID:23391594

One-shot LC-MS/MS analysis of post-translational modifications including oxidation and deamidation of rat lens α- and β-crystallins induced by γ-irradiation.

PubMed

Kim, Ingu; Saito, Takeshi; Fujii, Norihiko; Kanamoto, Takashi; Fujii, Noriko

2016-12-01

The eye lens is a transparent organ that functions to focus light and images on the retina. The transparency and high refraction of the lens are maintained by the function of α-, β-, and γ-crystallins. These long-lived proteins are subject to various post-translational modifications, such as oxidation, deamidation, truncation and isomerization, which occur gradually during the aging process. Such modifications, which are generated by UV light and oxidative stress, decrease crystallin solubility and lens transparency, and ultimately lead to the development of age-related cataracts. Here, we irradiated young rat lenses with γ-rays (5-500 Gy) and extracted the water-soluble (WS) and water-insoluble (WI) protein fractions. The WS and WI lens proteins were digested with trypsin, and the resulting peptides were analyzed by one-shot LC-MS/MS to determine the specific sites of oxidation of methionine and tryptophan, deamidation sites of asparagine and glutamine, and isomerization of aspartyl in rat α- and β-crystallins in the WS and WI fractions. Oxidation and deamidation occurred in several crystallins after irradiation at more than, respectively, 50 and 5 Gy; however, isomerization did not occur in any crystallin even after exposure to 500 Gy of irradiation. The number of oxidation and deamidation sites was much higher in the WI than in the WS fraction. Furthermore, the oxidation and deamidation sites in rat crystallins resemble those reported in crystallins from human age-related cataracts. Thus, this study on post-translational modifications of crystallins induced by ionizing irradiation may provide useful information relevant to the formation of human age-related cataracts.

Info-gap robust-satisficing model of foraging behavior: do foragers optimize or satisfice?

PubMed

Carmel, Yohay; Ben-Haim, Yakov

2005-11-01

In this note we compare two mathematical models of foraging that reflect two competing theories of animal behavior: optimizing and robust satisficing. The optimal-foraging model is based on the marginal value theorem (MVT). The robust-satisficing model developed here is an application of info-gap decision theory. The info-gap robust-satisficing model relates to the same circumstances described by the MVT. We show how these two alternatives translate into specific predictions that at some points are quite disparate. We test these alternative predictions against available data collected in numerous field studies with a large number of species from diverse taxonomic groups. We show that a large majority of studies appear to support the robust-satisficing model and reject the optimal-foraging model.

Role of strike-slip faulting in the evolution of allochthonous terranes in the Philippines

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

Karig, D.E.; Sarewitz, D.R.; Haeck, G.D.

1986-10-01

Concepts of allochthonous terrane transport and emplacement are dominated by the assumption that most terranes originate on the subducting plate, collide with the upper plate, and are emplaced there. Movement of terranes along the convergent margin is recognized but is generally attributed to postcollision slip. In the northern Philippines, allochthonous terranes originate primarily within the arc system, have been translated along it by strike-slip faults, and were emplaced by cessation of that slip. The authors suggest that in the Philippines some originally vertical strike-slip boundaries may have evolved into shallow-dipping sutures marked by fold and thrust systems. This mode ofmore » terrane evolution may be more common than generally appreciated, particularly in orogenic belts developed in response to oblique convergence.« less

Effect of pollen load size and source (self, outcross) on seed and fruit production in highbush blueberry cv. 'Bluecrop' (VACCINIUM CORYMBOSUM; Ericaceae).

PubMed

Dogterom, M H; Winston, M L; Mukai, A

2000-11-01

Reproductive fitness of a plant is ultimately determined by both number and quality of seed offspring. This is determined by sexual selection of pollen microspores and ovules during pollination and fertilization. These processes may include pollen competition and seed abortion, which reduce the number of microspores and ovules available for final seed production. Thus, even an excess of pollen microspores to ovules does not result in fertile seeds equal to ovule number. We investigated pollen requirements of highbush blueberry (Vaccinium corymbosum cultivar 'Bluecrop') for maximal seed production and how fertile seed number translates into fruit quality, since fruit quality would ultimately determine the dispersal of its offspring. We demonstrate that individual blueberry flowers with a mean of 106 ovules reach their maximum fruit set and mass and minimum time to ripen when 125 outcross pollen tetrads pollinate a flower, compared to 10 or 25. Three hundred tetrads resulted in the increase of fertile seeds, but did not result in a further increase of fruit mass or fruit set, or decrease in time to ripen. We also examined the effect of pure and mixed loads of self and outcross pollen (25 and 125 tetrads), and found no differences in fertile seed number, fruit mass, or percentage fruit set when pollen loads were either 25 self or outcross pollen tetrads, although number of days to ripen was significantly shorter by 8 d with 25 outcross tetrads. When the pollen load of 125 tetrads consisted of self or a 50:50 mixture of self and outcross pollen, fruit mass, days to ripen, and percentage fruit set were not different from loads of 125 outcross pollen. In addition, a pollen load of 25 outcross tetrads resulted in fertile seed number and fruit quality in between that of 25 self, and 125 self, 125 mixed, or 125 outcross tetrads. Large, small, and flat seed types were identified, and only large seeds (length = 1.7 mm) were fertile. These results improve our understanding of pollen load size and source requirements of a crop plant and the limits to pollen transfer when translated to fruit growth.

Combination of Pim kinase inhibitor, SGI-1776, with bendamustine in B-cell lymphoma

PubMed Central

Yang, Qingshan; Chen, Lisa S; Neelapu, Sattva S.; Gandhi, Varsha

2013-01-01

SGI-1776 is a small molecule Pim kinase inhibitor that primarily targets c-Myc-driven transcription and cap-dependent translation in mantle cell lymphoma (MCL) cells. Bendamustine is an alkylating chemotherapeutic agent approved for use in B-cell lymphoma that is known to induce DNA damage and to initiate response to repair. We hypothesized that while each drug leads to the effects as stated above, combination of these drugs will enhance SGI-1776-induced inhibition of global transcription and translation processes, while promoting bendamustine-triggered decrease of DNA synthesis and DNA damage response in B-cell lymphoma. Both SGI-1776 and bendamustine as single agents effectively induced apoptosis and when used in combination, additive effect in cell killing was observed in MCL cell lines, JeKo-1 and Mino, as well as MCL and splenic marginal zone lymphoma (a type of B-cell lymphoma) primary cells. As expected, SGI-1776 was effective in inducing decrease of global RNA and protein synthesis, while bendamustine significantly inhibited DNA synthesis and generated DNA damage response. When used in combination, effects were intensified in DNA, RNA and protein syntheses compared to single agent treatments. Together, these data provided foundation and suggested feasibility of using Pim kinase inhibitor in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma. PMID:24290221

Low-Power and High-Speed Technique for logic Gates in 20nm Double-Gate FinFET Technology

NASA Astrophysics Data System (ADS)

Priydarshi, A.; Chattopadhyay, M. K.

2016-10-01

The FinFET is the leading example of multigate MOSFETS to substitute conventional single gate MOSFETs for ultimate scaling [1], The FinFET structure is a combination of a thin channel region and a double gate to suppress the short channel effects (SCEs) and Vthvariation [2], By using FinFET,figure of merits viz, ION, IOFF, output resistance, propagation delay, noise margin and leakage power, can be improved for ultra low power and high performance applications[3]. In this paper, a new high speed low power dynamic circuit design technique has been proposed using 20nm FinFETs. By applying the appropriate clock and sleep signal to the back gates of the FinFETs, the proposed circuit can efficiently control the dynamic power, During the pre-charging period, Vth of PMOS is controlled low so that a fast precharging can occur;

A new Early Cretaceous eutherian mammal from the Sasayama Group, Hyogo, Japan

PubMed Central

Kusuhashi, Nao; Tsutsumi, Yukiyasu; Saegusa, Haruo; Horie, Kenji; Ikeda, Tadahiro; Yokoyama, Kazumi; Shiraishi, Kazuyuki

2013-01-01

We here describe a new Early Cretaceous (early Albian) eutherian mammal, Sasayamamylos kawaii gen. et sp. nov., from the ‘Lower Formation’ of the Sasayama Group, Hyogo Prefecture, Japan. Sasayamamylos kawaii is characterized by a robust dentary, a distinct angle on the ventral margin of the dentary at the posterior end of the mandibular symphysis, a lower dental formula of 3–4 : 1 : 4 : 3, a robust lower canine, a non-molariform lower ultimate premolar, and a secondarily reduced entoconid on the molars. To date, S. kawaii is the earliest known eutherian mammal possessing only four premolars, which demonstrates that the reduction in the premolar count in eutherians started in the late Early Cretaceous. The occurrence of S. kawaii implies that the relatively rapid diversification of eutherians in the mid-Cretaceous had already started by the early Albian. PMID:23536594

Structural geology of the African rift system: Summary of new data from ERTS-1 imagery. [Precambrian influence

NASA Technical Reports Server (NTRS)

Mohr, P. A.

1974-01-01

ERTS imagery reveals for the first time the structural pattern of the African rift system as a whole. The strong influence of Precambrian structures on this pattern is clearly evident, especially along zones of cataclastic deformation, but the rift pattern is seen to be ultimately independent in origin and nature from Precambrian tectonism. Continuity of rift structures from one swell to another is noted. The widening of the Gregory rift as its northern end reflects an underlying Precambrian structural divergence, and is not a consequence of reaching the swell margin. Although the Western Rift is now proven to terminate at the Aswa Mylonite Zone, in southern Sudan, lineaments extend northeastwards from Lake Albert to the Eastern Rift at Lake Stefanie. The importance of en-echelon structures in the African rifts is seen to have been exaggerated.

Changes in forest productivity across Alaska consistent with biome shift.

PubMed

Beck, Pieter S A; Juday, Glenn P; Alix, Claire; Barber, Valerie A; Winslow, Stephen E; Sousa, Emily E; Heiser, Patricia; Herriges, James D; Goetz, Scott J

2011-04-01

Global vegetation models predict that boreal forests are particularly sensitive to a biome shift during the 21st century. This shift would manifest itself first at the biome's margins, with evergreen forest expanding into current tundra while being replaced by grasslands or temperate forest at the biome's southern edge. We evaluated changes in forest productivity since 1982 across boreal Alaska by linking satellite estimates of primary productivity and a large tree-ring data set. Trends in both records show consistent growth increases at the boreal-tundra ecotones that contrast with drought-induced productivity declines throughout interior Alaska. These patterns support the hypothesized effects of an initiating biome shift. Ultimately, tree dispersal rates, habitat availability and the rate of future climate change, and how it changes disturbance regimes, are expected to determine where the boreal biome will undergo a gradual geographic range shift, and where a more rapid decline. © 2011 Blackwell Publishing Ltd/CNRS.

The ambivert: A failed attempt at a normal personality.

PubMed

Davidson, Ian J

2017-09-01

Recently, attention has been drawn toward an overlooked and nearly forgotten personality type: the ambivert. This paper presents a genealogy of the ambivert, locating the various contexts it traversed in order to highlight the ways in which these places and times have interacted and changed-ultimately elucidating our current situation. Proposed by Edmund S. Conklin in 1923, the ambivert only was meant for normal persons in between the introvert and extravert extremes. Although the ambivert could have been taken up by early personality psychologists who were transitioning from the study of the abnormal to the normal, it largely failed to gain traction. Whether among psychoanalysts, psychiatrists, or applied and personality psychologists, the ambivert was personality non grata. It was only within the context of Eysenck's integrative view of types and traits that the ambivert marginally persisted up to the present day and is now the focus of sales management and popular psychology. © 2017 Wiley Periodicals, Inc.

The Fate and Impact of Internal Waves in Nearshore Ecosystems

NASA Astrophysics Data System (ADS)

Woodson, C. B.

2018-01-01

Internal waves are widespread features of global oceans that play critical roles in mixing and thermohaline circulation. Similarly to surface waves, internal waves can travel long distances, ultimately breaking along continental margins. These breaking waves can transport deep ocean water and associated constituents (nutrients, larvae, and acidic low-oxygen waters) onto the shelf and locally enhance turbulence and mixing, with important effects on nearshore ecosystems. We are only beginning to understand the role internal waves play in shaping nearshore ecosystems. Here, I review the physics of internal waves in shallow waters and identify two commonalities among internal waves in the nearshore: exposure to deep offshore waters and enhanced turbulence and mixing. I relate these phenomena to important ecosystem processes ranging from extreme events to fertilization success to draw general conclusions about the influence of internal waves on ecosystems and the effects of internal waves in a changing climate.

CFD Assessment of Aerodynamic Degradation of a Subsonic Transport Due to Airframe Damage

NASA Technical Reports Server (NTRS)

Frink, Neal T.; Pirzadeh, Shahyar Z.; Atkins, Harold L.; Viken, Sally A.; Morrison, Joseph H.

2010-01-01

A computational study is presented to assess the utility of two NASA unstructured Navier-Stokes flow solvers for capturing the degradation in static stability and aerodynamic performance of a NASA General Transport Model (GTM) due to airframe damage. The approach is to correlate computational results with a substantial subset of experimental data for the GTM undergoing progressive losses to the wing, vertical tail, and horizontal tail components. The ultimate goal is to advance the probability of inserting computational data into the creation of advanced flight simulation models of damaged subsonic aircraft in order to improve pilot training. Results presented in this paper demonstrate good correlations with slope-derived quantities, such as pitch static margin and static directional stability, and incremental rolling moment due to wing damage. This study further demonstrates that high fidelity Navier-Stokes flow solvers could augment flight simulation models with additional aerodynamic data for various airframe damage scenarios.

Geophysical Data Define Boundaries and Sub-Regions of the Northern Gulf of Mexico Basin: Structural Histories and Causes are Hypothesized.

NASA Astrophysics Data System (ADS)

Kinsland, G. L.

2017-12-01

Within the last several years new types of geophysical data of the southern margin of the North American Craton and the Northern Gulf of Mexico Basin (NGoMB) have become available, e.g., results from the USArray experiment, high resolution satellite gravity data of the GoM itself and new heat flow data. These data when combined with previously existing geophysical data (gravity, magnetic and seismic) and shallow structural data offer new insights into the boundaries and sub-regions of the NGoMB. I offer hypotheses for the development of the structures of the buried crust and upper mantle which cause these features. Of particular interest might be my suggestion that the NGoMB might have extended in a southeasterly direction prior to the counter-clockwise rotation of the Yucatan Peninsula which ultimately resulted in the GoM.

The Case for Same-Sex Marriage Before the European Court of Human Rights.

PubMed

Hamilton, Frances

2017-09-26

For proponents of same-sex marriage, this essay sets forward a critical analysis of relevant arguments before the European Court of Human Rights. The privacy aspect of Article 8 European Convention of Human Rights will never be a successful argument with reference to marriage, which involves a public status. The equality argument (Article 14) is useful in addressing this issue with its close connections with citizenship, symbolic value, and proven record internationally. Difficulties remain with the equality argument; its conditional status, the width of the margin of appreciation allocated, and the need for an equality comparator. The equality argument needs reinforcement by use alongside a developing family law argument under Article 8 and a dynamically interpreted Article 12 (right to marry) argument. Ultimately, the success of any argument depends on convincingly influencing the European Court to consider that sufficient consensus has developed among Member States of the Council of Europe.

The healing of disturbed hillslopes by gully gravure

USGS Publications Warehouse

Osterkamp, W.R.; Toy, T.J.

1994-01-01

Results of accelerated erosion on certain constructed surfaces in southeastern Arizona appear similar to those described by Bryan as gully gravure. Twenty cross-section excavations in eight rills inclised into silt-rich lacustrine and fluvial deposits reveal partial filling of the rills by debris derived from overyling fluvial sand, gravel, and cobbles. Interstices of the coarse material gradually fill with fine-grained erosion products, decreasing permeability of the fill and deflecting subsequent runoff to the margins of the fill. Rills and rill fillings thus increase in width with time, and complete veneering of the surface by coarse debris ultimately may occur. Through incision, filling, lateral planation, and armoring, channels of the dissected surface heal and the new hillslope approaches an equilibrium condition. Natural hillslopes in the area with similar geologic conditions have inclinations of 16??-22??, have generally unbroken veneers of coarse debris, and appear subject to the same erosional processes identified at constructed hillslopes. -from Authors

The Fate and Impact of Internal Waves in Nearshore Ecosystems.

PubMed

Woodson, C B

2018-01-03

Internal waves are widespread features of global oceans that play critical roles in mixing and thermohaline circulation. Similarly to surface waves, internal waves can travel long distances, ultimately breaking along continental margins. These breaking waves can transport deep ocean water and associated constituents (nutrients, larvae, and acidic low-oxygen waters) onto the shelf and locally enhance turbulence and mixing, with important effects on nearshore ecosystems. We are only beginning to understand the role internal waves play in shaping nearshore ecosystems. Here, I review the physics of internal waves in shallow waters and identify two commonalities among internal waves in the nearshore: exposure to deep offshore waters and enhanced turbulence and mixing. I relate these phenomena to important ecosystem processes ranging from extreme events to fertilization success to draw general conclusions about the influence of internal waves on ecosystems and the effects of internal waves in a changing climate.

Dosimetric and geometric evaluation of a hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy

PubMed Central

Liu, Han; Wu, Qiuwen

2011-01-01

For prostate cancer patients, online image-guided (IG) radiotherapy has been widely used in clinic to correct the translational inter-fractional motion at each treatment fraction. For uncertainties that cannot be corrected online, such as rotation and deformation of the target volume, margins are still required to be added to the clinical target volume (CTV) for the treatment planning. Offline adaptive radiotherapy has been implemented to optimize the treatment for each individual patient based on the measurements at early stages of treatment process. It has been shown that offline adaptive radiotherapy can effectively reduce the required margin. Recently a hybrid strategy of offline adaptive replanning and online IG was proposed and the geometric evaluation was performed. It was found that the planning margins can be further reduced by 1–2 mm compared to online IG only strategy. The purpose of this study was to investigate the dosimetric benefits of such hybrid strategy on the target and organs at risk (OARs). A total of 420 repeated helical computed tomography (HCT) scans from 28 patients were included in the study. Both low-risk patients (LRP, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles, SV) were included in the simulation. Two registration methods, based on center-of-mass (COM) shift of prostate only and prostate plus SV, were performed for IRP. The intensity modulated radiotherapy (IMRT) was used in the simulation. Criteria on both cumulative dose and fractional doses were evaluated. Furthermore, the geometric evaluation was extended to investigate the optimal number of fractions necessary to construct the internal target volume (ITV) for the hybrid strategy. The dosimetric margin improvement was smaller than its geometric counterpart and was in the range of 0 mm to 1 mm. The optimal number of fractions necessary for the ITV construction is 2 for LRP and 3–4 for IRP in a hypofractionation protocol. A new cumulative index of target volume (CITV) was proposed for the evaluation of adaptive radiotherapy strategies, and it was found that it had the advantages over other indices in evaluating different adaptive radiotherapy strategies. PMID:21772083

Dosimetric and geometric evaluation of a hybrid strategy of offline adaptive planning and online image guidance for prostate cancer radiotherapy.

PubMed

Liu, Han; Wu, Qiuwen

2011-08-07

For prostate cancer patients, online image-guided (IG) radiotherapy has been widely used in clinic to correct the translational inter-fractional motion at each treatment fraction. For uncertainties that cannot be corrected online, such as rotation and deformation of the target volume, margins are still required to be added to the clinical target volume (CTV) for the treatment planning. Offline adaptive radiotherapy has been implemented to optimize the treatment for each individual patient based on the measurements at early stages of treatment process. It has been shown that offline adaptive radiotherapy can effectively reduce the required margin. Recently a hybrid strategy of offline adaptive replanning and online IG was proposed and the geometric evaluation was performed. It was found that the planning margins can further be reduced by 1-2 mm compared to online IG only strategy. The purpose of this study was to investigate the dosimetric benefits of such a hybrid strategy on the target and organs at risk. A total of 420 repeated helical computed tomography scans from 28 patients were included in the study. Both low-risk patients (LRP, CTV = prostate) and intermediate-risk patients (IRP, CTV = prostate + seminal vesicles, SV) were included in the simulation. Two registration methods, based on center-of-mass shift of prostate only and prostate plus SV, were performed for IRP. The intensity-modulated radiotherapy was used in the simulation. Criteria on both cumulative and fractional doses were evaluated. Furthermore, the geometric evaluation was extended to investigate the optimal number of fractions necessary to construct the internal target volume (ITV) for the hybrid strategy. The dosimetric margin improvement was smaller than its geometric counterpart and was in the range of 0-1 mm. The optimal number of fractions necessary for the ITV construction is 2 for LRPs and 3-4 for IRPs in a hypofractionation protocol. A new cumulative index of target volume was proposed for the evaluation of adaptive radiotherapy strategies, and it was found that it had the advantages over other indices in evaluating different adaptive radiotherapy strategies.

Physical Processes Contributing To Small-scale Vertical Movements During Changing Inplane Stresses In Rift Basins and At Passive Continental Margins

NASA Astrophysics Data System (ADS)

Paulsen, G. E.; Nielsen, S. B.; Hansen, D. L.

The vertical movements during a regional stress reversal in a rifted basin or on a passive continental margin are examined using a numerical 2D thermo-mechanical finite element model with a visco-elastic-plastic rheology. Three different physical mechanisms are recognized in small-scale vertical movements at small inplane force variations: elastic dilatation, elastic flexure, and permanent deformation. Their rela- tive importance depend on the applied force, the duration of the force, and the thermal structure of the lithosphere. Elastic material dilatation occurs whenever the stress state changes. A reversal from extension to compression therefore immediately leads to elastic dilatation, and re- sults in an overall subsidence of the entire profile. Simultaneously with dilatation the lithosphere reacts with flexure. The significance of the flexural component strongly depends on the thermal structure of the lithosphere. The polarity and amplitude of the flexure depends on the initial (before compression) loading of the lithosphere. Gener- ally, the flexural effects lead to subsidence of the overdeep in the landward part of the basin and a small amount of uplift at the basin flanks. The amplitudes of the flexural response are small and comparable with the amplitudes of the elastic dilatation. With continuing compression permanent deformation and lithospheric thickening becomes increasingly important. Ultimately, the thickened part of the lithosphere stands out as an inverted zone. The amount of permanent deformation is directly connected with the size and duration of the applied force, but even a relatively small force leads to inversion tectonics in the landward part of the basin. The conclusions are: 1) small stress induced vertical movements in rift basins and at passive continental margins are the result of a complex interaction of at least three different processes, 2) the total sediment loaded amplitudes resulting from these pro- cesses are small (2-300 m) for inplane forces up to 1.5·1012 N/m.

Frozen section analysis of margins for head and neck tumor resections: reduction of sampling errors with a third histologic level.

PubMed

Olson, Stephen M; Hussaini, Mohammad; Lewis, James S

2011-05-01

Frozen section analysis is an essential tool for assessing margins intra-operatively to assure complete resection. Many institutions evaluate surgical defect edge tissue provided by the surgeon after the main lesion has been removed. With the increasing use of transoral laser microsurgery, this method is becoming even more prevalent. We sought to evaluate error rates at our large academic institution and to see if sampling errors could be reduced by the simple method change of taking an additional third section on these specimens. All head and neck tumor resection cases from January 2005 through August 2008 with margins evaluated by frozen section were identified by database search. These cases were analyzed by cutting two levels during frozen section and a third permanent section later. All resection cases from August 2008 through July 2009 were identified as well. These were analyzed by cutting three levels during frozen section (the third a 'much deeper' level) and a fourth permanent section later. Error rates for both of these periods were determined. Errors were separated into sampling and interpretation types. There were 4976 total frozen section specimens from 848 patients. The overall error rate was 2.4% for all frozen sections where just two levels were evaluated and was 2.5% when three levels were evaluated (P=0.67). The sampling error rate was 1.6% for two-level sectioning and 1.2% for three-level sectioning (P=0.42). However, when considering only the frozen section cases where tumor was ultimately identified (either at the time of frozen section or on permanent sections) the sampling error rate for two-level sectioning was 15.3 versus 7.4% for three-level sectioning. This difference was statistically significant (P=0.006). Cutting a single additional 'deeper' level at the time of frozen section identifies more tumor-bearing specimens and may reduce the number of sampling errors.

Erosional dynamics, flexural isostasy, and long-lived escarpments: A numerical modeling study

NASA Technical Reports Server (NTRS)

Tucker, Gregory E.; Slingerland, Rudy L.

1994-01-01

Erosional escarpments common features of high-elevation rifted continets. Fission track data suffest that these escarpments form by base level lowering and/or marginal uplift during rifting, followed by lateral retreat of an erosion front across tens to hundreds of kioometers. Previous modeling studies have shown that this characteristic pattern of denudation can have a profound impact upon marginal isostatic uplift and the evolution of offshore sedimentary basins. Yet at present there is only a rudimentary understanding of the geomorphic mechanisms capable of driving such prolonged escarpment retreat. In this study we present a nonlinear, two-dimensional landscape evolution model tha tis used to asses the necessary and sufficient conditions for long-term retreat of a rift-generated escarpment. The model represents topography as a grid of cells, with drainage networkds evolving as water flows across the grid in the direction of steepest descent. The model accounts for sediment production by weathering, fluvial sediment transport, bedrock channel erosion, and hillslope sediment transport by diffusive mechanisms and by mass failure. Numerical experiments presented explore the effects of different combinations of erosion processes and of dynamic coupling between denudation and flexural isostatic uplift. Model results suggest that the necessary and sufficient conditions for long-term escarpment retreat are (1) incising bedrock channels in which the erosion rate increases with increasing drainage area, so that the channels steepen and propagate headward; (2) a low rate of sediment production relative to sediment transport efficiency, which promotes relief-generating processes over diffusive ones; (3) high continental elevation, which allows greater freedom for fluvial dissection; and (4) any process, including flexural isostatic uplift, that helps to maintain a drainage divide near an escarpment crest. Flexural isostatic uplift also facilitates escarpment, thereby increasing channel gradients and accelerating erosion which in turn generates additional isostatic uplift. Of all the above conditions, high continental elevation is common ot most rift margin escarpments and may ultimately be the most important factor.

Use of Ramped PyrOx 14C dating to simultaneously determine the organic carbon age and carbonate material age of Antarctic marginal sediments

NASA Astrophysics Data System (ADS)

Reese, D.; DeCesare, M.; Subt, C.; Bart, P. J.; Wellner, J. S.; Rosenheim, B. E.

2016-12-01

Chronicling deglaciation rates and style in Antarctic margin sediment is difficult because of low preservation/deposition of carbonate foraminiferal tests as well as incorporation of pre-aged organic carbon from carbonaceous rocks. When carbonates for radiocarbon dating are absent, acid-insoluble organic matter (AIOM) 14C dates are often used as an alternative and providing reliable chronologies in some locations. Results obtained by this method can cause difficulties such as false age reversals and ambiguity due to contamination with pre-aged carbon (Rosenheim et. al., 2008; Subt et al., 2016). Ramped PyrOx 14C dating has exploited the higher thermochemical stability of pre-aged carbon to separate carbon dating to the time of sediment deposition, and recently has produced chronologies similar to foraminifera-based chronologies (Subt et al., 2016). Samples for Ramped PyrOx 14C dating have generally been treated with acid to remove carbonates, and thus some acid soluble organic matter. In an effort to minimize the alteration of the organic matter, we apply Ramped PyrOx 14C dating to samples that have been both treated with 1N HCl and left untreated. Untreated samples display a characteristic large, sharp peak at higher temperatures than pyrolysis of organic matter that we interpret as carbonate decomposition. These carbonate decomposition peaks are characteristically sharp and occur at higher temperatures than the maximum evolution of CO2 from the organic matter in the sample. We isolated these peaks for comparison between known carbonate ages from picked foraminifera and low-temperature Ramped PyrOx splits from acid treated samples. We will discuss the treatment of the suite of 14C ages with reconciliation of two dating methods in mind. Ultimately, this approach offers promise for a single treatment of Antarctic margin sediments that provides chronologies from both carbonate and organic material.

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

Gougar, Hans

This document outlines the development of a high fidelity, best estimate nuclear power plant severe transient simulation capability that will complement or enhance the integral system codes historically used for licensing and analysis of severe accidents. As with other tools in the Risk Informed Safety Margin Characterization (RISMC) Toolkit, the ultimate user of Enhanced Severe Transient Analysis and Prevention (ESTAP) capability is the plant decision-maker; the deliverable to that customer is a modern, simulation-based safety analysis capability, applicable to a much broader class of safety issues than is traditional Light Water Reactor (LWR) licensing analysis. Currently, the RISMC pathway’s majormore » emphasis is placed on developing RELAP-7, a next-generation safety analysis code, and on showing how to use RELAP-7 to analyze margin from a modern point of view: that is, by characterizing margin in terms of the probabilistic spectra of the “loads” applied to systems, structures, and components (SSCs), and the “capacity” of those SSCs to resist those loads without failing. The first objective of the ESTAP task, and the focus of one task of this effort, is to augment RELAP-7 analyses with user-selected multi-dimensional, multi-phase models of specific plant components to simulate complex phenomena that may lead to, or exacerbate, severe transients and core damage. Such phenomena include: coolant crossflow between PWR assemblies during a severe reactivity transient, stratified single or two-phase coolant flow in primary coolant piping, inhomogeneous mixing of emergency coolant water or boric acid with hot primary coolant, and water hammer. These are well-documented phenomena associated with plant transients but that are generally not captured in system codes. They are, however, generally limited to specific components, structures, and operating conditions. The second ESTAP task is to similarly augment a severe (post-core damage) accident integral analyses code with high fidelity simulations that would allow investigation of multi-dimensional, multi-phase containment phenomena that are only treated approximately in established codes.« less

Sedimentologic and paleoclimatic reconstructions of carbonate factory evolution in the Alborz Basin (northern Iran) indicate a global response to Early Carboniferous (Tournaisian) glaciations

NASA Astrophysics Data System (ADS)

Sardar Abadi, Mehrdad; Kulagina, Elena I.; Voeten, Dennis F. A. E.; Boulvain, Frédéric; Da Silva, Anne-Christine

2017-03-01

The Lower Carboniferous Mobarak Formation records the development of a storm-sensitive pervasive carbonate factory on the southern Paleo-Tethyan passive margin following the opening of the Paleo-Tethys Ocean into the Alborz Basin along the northern margin of Gondwana. Its depositional facies encompass inner ramp peritidal environments, peloidal to crinoidal shoals, storm to fair-weather influenced mid-ramps, proximal to distal shell beds and low energy outer ramps. Sedimentological analyses and foraminiferal biostratigraphy reveal four events affecting carbonate platform evolution in the Alborz Basin during the Lower Carboniferous: (1) A transgression following global temperature rise in the Early Tournaisian (middle Hastarian) caused the formation of thick-bedded argillaceous limestones. This interval correlates with Early Tournaisian nodular to argillaceous limestones in the Moravia Basin (Lisen Formation, Czech Republic), the Dinant Basin (Pont d'Arcole Formation, Belgium), and at the Rhenish Slate Mountains (Lower Alum shale, Germany). (2) Late Hastarian-early Ivorian glaciations previously identified in Southern Gondwana but had not yet recognized in Northern Gondwana were recorded through a sequence boundary. (3) During the Late Tournaisian-Early Visean?, a differential block faulting regime along the basin's margin caused uplift of the westernmost parts of the Alborz Basin and resulted in subsidence in the eastern part of the central basin. This tectonically controlled shift in depositional regime caused vast sub-aerial exposure and brecciation preserved in the top of the Mobarak Formation in the western portion of the Central Alborz Basin. (4) Tectonic activity coinciding with a progressive, multiphase sea level drop caused indirectly by the Viséan and Serpukhovian glaciations phases ultimately led to the stagnation of the carbonate factory. Paleothermometry proxies, the presence of foraminiferal taxa with a northern Paleo-Tethyan affinity and evidence for arid conditions in the terrestrial hinterland place the Alborz Basin at lower latitudes than the approximately 45ο-50ο southern paleolatitude reported thus far.

Poroelastic Parameters of Peru Margin Sediments: Implications for Flow and Transport at Multiple Scales in the Marine Biosphere

NASA Astrophysics Data System (ADS)

Gettemy, G. L.; Cikoski, C.; Tobin, H. J.

2004-12-01

As part of a broader investigation of the deep marine subsurface environment, the first biosphere-focused drilling expedition, Leg 201, of the Ocean Drilling Program (ODP) occupied five unique sites in the Peru Margin (in a 1200 km2 region centered at 10 S, 80E). These sites represent the entire range of shallow biogeological conditions associated with this convergent margin:deep-water, mixed clay-pelagic sediments ocean-ward of the trench; slope-apron and prism toe sediments at the deformation front; and several distinct lithostratigraphic sequences on the continental shelf. Microbial enumeration and pore-water geochemistry results show that each particular site is both consistent and unique--consistent in terms of general biotic quantity and activity as predicted by energy flux and redox potential given the depositional environment and sedimentary record, but unique at key biogeological boundaries such as lithologic and/or physical property interfaces. This research addresses questions related to our understanding of how and why these boundaries form by looking at poroelastic and hydrologic parameters measured at multiple scales, from sub-millimeter to several centimeters. The issue of measurement scale, especially in regard to permeability and diffusivity characterization, is vital to interpreting observations of biologically-mediated diagenetic fronts (e.g., dolomitic lenses, depth- or time-varying barite fronts). These parameters are derived from (i) hydrologic and wave propagation experiments, (ii) SEM images, and (iii) shipboard split-core measurements, and structured in a modified Biot poroelasticity framework. This approach also allows quantification of the local heterogeneity of these parameters at the scale applicable to (and controlled by) microbial life; these results can then be used to formulate predictive models of the impact of biogeochemical processes. Ultimately, these models could then be used in interpretation of new remote-sensed data (e.g., from borehole tools, high-frequency backscatter devices), a fundamental challenge for all types of biospheric imaging everywhere.

Seamount subduction underneath an accretionary wedge: modelling mass wasting and wedge collapse

NASA Astrophysics Data System (ADS)

Mannu, Utsav; Ueda, Kosuke; Willett, Sean; Gerya, Taras; Strasser, Michael

2017-04-01

Seamounts (h >1 km) and knolls (h = 500 m-1000 m) cover about one-fifth of the total ocean floor area. These topographical highs of the ocean floor eventually get subducted. Subduction of these topographical features leads to severe deformation of the overriding plate and can cause extensive tectonic erosion and mass wasting of the frontal prism, which can ultimately cause a forearc wedge collapse. Large submarine landslides and the corresponding wedge collapse have previously been reported, for instance, in the northern part of the Hikurangi margin where the landslide is known as the giant Ruatoria debris avalanche, and have also been frequently reported in several seismic sections along the Costa Rica margin. Size and frequency relation of landslides suggest that the average size of submarine landslides in margins with rough subducting plates tends to be larger. However, this observation has not yet been tested or explained by physical models. In numerical subduction models, landslides take place, if at all, on a much larger timescale (in the order of 104-105 years, depending on the time steps of the model) than in natural cases. On the other hand, numerical models simulating mass wasting events such as avalanches and submarine landslides, typically model single events at a much smaller spatio-temporal domain, and do not consider long-term occurrence patterns of freely forming landslides. In this contribution, we present a multi-scale nested numerical approach to emulate short-term landslides within long-term progressive subduction. The numerical approach dynamically produces instantaneous submarine landslides and the resulting debris flow in the spatially and temporally refined inner model. Then we apply these convoluted changes in topography (e.g. due to the submarine landslide etc.) back to an outer larger-scale model instance that addresses wedge evolution. We use this approach to study the evolution of the accretionary wedge during seamount subduction.

Cleavage of a Gulf of Mexico Loop Current eddy by a deep water cyclone

NASA Astrophysics Data System (ADS)

Biggs, D. C.; Fargion, G. S.; Hamilton, P.; Leben, R. R.

1996-09-01

Eddy Triton, an anticyclonic eddy shed by the Loop Current in late June 1991, drifted SW across the central Gulf of Mexico in the first 6 months of 1992, along the ``southern'' of the three characteristic drift paths described by Vukovich and Crissman [1986] from their analyses of 13 years of advanced very high resolution radiometer sea surface temperature data. An expendable bathythermograph (XBT) and conductivity-temperature-depth (CTD) transect of opportunity through Triton at eddy age 7 months in January 1992 found that eddy interior stood 23 dyn. cm higher than periphery; this gradient drove an anticyclonic swirl transport of 9-10 Sv relative to 800 dbar. At eddy age 9-10 months and while this eddy was in deep water near 94°W, it interacted with a mesoscale cyclonic circulation and was cleaved into two parts. The major (greater dynamic centimeters) piece drifted NW to end up in the ``eddy graveyard'' in the NW corner of the gulf, while the minor piece drifted SW and reached the continental margin of the western gulf off Tuxpan. This southern piece of Eddy Triton then turned north to follow the 2000-m isobath to about 24°N and later coalesced with what remained of the major fragment. Because Eddy Triton's cleavage took place just before the start of marine mammals (GulfCet) and Louisiana-Texas physical oceanography (LATEX) field programs, the closely spaced CTD, XBT, and air dropped XBT (AXBT) data that were gathered on the continental margin north of 26°N in support of these programs allow a detailed look at the northern margin of the larger fragment of this eddy. Supporting data from the space-borne altimeters on ERS 1 and TOPEX/POSEIDON allow us to track both pieces of Eddy Triton in the western Gulf and follow their spin down in dynamic height, coalescence, and ultimate entrainment in January 1993 into another anticyclonic eddy (Eddy U).

Phosphate rock formation and marine phosphorus geochemistry: the deep time perspective.

PubMed

Filippelli, Gabriel M

2011-08-01

The role that phosphorite formation, the ultimate source rock for fertilizer phosphate reserves, plays in the marine phosphorus (P) cycle has long been debated. A shift has occurred from early models that evoked strikingly different oceanic P cycling during times of widespread phosphorite deposition to current thinking that phosphorite deposits may be lucky survivors of a series of inter-related tectonic, geochemical, sedimentological, and oceanic conditions. This paradigm shift has been facilitated by an awareness of the widespread nature of phosphogenesis-the formation of authigenic P-bearing minerals in marine sediments that contributes to phosphorite formation. This process occurs not just in continental margin sediments, but in deep sea oozes as well, and helps to clarify the driving forces behind phosphorite formation and links to marine P geochemistry. Two processes come into play to make phosphorite deposits: chemical dynamism and physical dynamism. Chemical dynamism involves the diagenetic release and subsequent concentration of P-bearing minerals particularly in horizons, controlled by a number of sedimentological and biogeochemical factors. Physical dynamism involves the reworking and sedimentary capping of P-rich sediments, which can either concentrate the relatively heavy and insoluble disseminated P-bearing minerals or provide an episodic change in sedimentology to concentrate chemically mobilized P. Both processes can result from along-margin current dynamics and/or sea level variations. Interestingly, net P accumulation rates are highest (i.e., the P removal pump is most efficient) when phosphorites are not forming. Both physical and chemical pathways involve processes not dominant in deep sea environments and in fact not often coincide in space and time even on continental margins, contributing to the rarity of high-quality phosphorite deposits and the limitation of phosphate rock reserves. This limitation is becoming critical, as the human demand for P far outstrips the geologic replacement for P and few prospects exist for new discoveries of phosphate rock. Copyright © 2011 Elsevier Ltd. All rights reserved.

Investigating the effects of visual distractors on the performance of a motor imagery brain-computer interface.

PubMed

Emami, Zahra; Chau, Tom

2018-06-01

Brain-computer interfaces (BCIs) allow users to operate a device or application by means of cognitive activity. This technology will ultimately be used in real-world environments which include the presence of distractors. The purpose of the study was to determine the effect of visual distractors on BCI performance. Sixteen able-bodied participants underwent neurofeedback training to achieve motor imagery-guided BCI control in an online paradigm using electroencephalography (EEG) to measure neural signals. Participants then completed two sessions of the motor imagery EEG-BCI protocol in the presence of infrequent, small visual distractors. BCI performance was determined based on classification accuracy. The presence of distractors was found to affect motor imagery-specific patterns in mu and beta power. However, the distractors did not significantly affect the BCI classification accuracy; across participants, the mean classification accuracy was 81.5 ± 14% for non-distractor trials, and 78.3 ± 17% for distractor trials. This minimal consequence suggests that the BCI was robust to distractor effects, despite motor imagery-related brain activity being attenuated amid distractors. A BCI system that mitigates distraction-related effects may improve the ease of its use and ultimately facilitate the effective translation of the technology from the lab to the home. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

SU-D-BRA-02: Motion Assessment During Open Face Mask SRS Using CBCT and Surface Monitoring

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

Williams, BB; Fox, CJ; Hartford, AC

Purpose: To assess the robustness of immobilization using open-face mask technology for linac-based stereotactic radiosurgery (SRS) with multiple non-coplanar arcs via repeated CBCT acquisition, with comparison to contemporaneous optical surface tracking data. Methods: 25 patients were treated in open faced masks with cranial SRS using 3–4 non-coplanar arcs. Repeated CBCT imaging was performed to verify the maintenance of proper patient positioning during treatment. Initial patient positioning was performed based on prescribed shifts and optical surface tracking. Positioning refinements employed rigid 3D-matching of the planning CT and CBCT images and were implemented via automated 6DOF couch control. CBCT imaging was repeatedmore » following the treatment of all non-transverse beams with associated couch kicks. Detected patient translations and rotations were recorded and automatically corrected. Optical surface tracking was applied throughout the treatments to monitor motion, and this contemporaneous patient positioning data was recorded to compare against CBCT data and 6DOF couch adjustments. Results: Initial patient positions were refined on average by translations of 3±1mm and rotations of ±0.9-degrees. Optical surface tracking corroborated couch corrections to within 1±1mm and ±0.4-degrees. Following treatment of the transverse and subsequent superior-oblique beam, average translations of 0.6±0.4mm and rotations of ±0.4-degrees were reported via CBCT, with optical surface tracking in agreement to within 1.1±0.6mm and ±0.6-degrees. Following treatment of the third beam, CBCT indicated additional translations of 0.4±0.2mm and rotations of ±0.3-degrees. Cumulative couch corrections resulted in 0.7 ± 0.4mm average magnitude translations and rotations of ±0.4-degrees. Conclusion: Based on CBCT measurements of patients during SRS, the open face mask maintained patient positioning to within 1.5mm and 1-degree with >95% confidence. Patient positioning determined by optical surface tracking agreed with CBCT assessment to within 1±1mm and ±0.6-degree rotations. These data support the use of 1–2mm PTV margins and repeated CBCT to maintain stereotactic positioning tolerances.« less

Flow of variably fluidized granular masses across three-dimensional terrain I. Coulomb mixture theory

USGS Publications Warehouse

Iverson, R.M.; Denlinger, R.P.

2001-01-01

Rock avalanches, debris flows, and related phenomena consist of grain-fluid mixtures that move across three-dimensional terrain. In all these phenomena the same basic forces, govern motion, but differing mixture compositions, initial conditions, and boundary conditions yield varied dynamics and deposits. To predict motion of diverse grain-fluid masses from initiation to deposition, we develop a depth-averaged, threedimensional mathematical model that accounts explicitly for solid- and fluid-phase forces and interactions. Model input consists of initial conditions, path topography, basal and internal friction angles of solid grains, viscosity of pore fluid, mixture density, and a mixture diffusivity that controls pore pressure dissipation. Because these properties are constrained by independent measurements, the model requires little or no calibration and yields readily testable predictions. In the limit of vanishing Coulomb friction due to persistent high fluid pressure the model equations describe motion of viscous floods, and in the limit of vanishing fluid stress they describe one-phase granular avalanches. Analysis of intermediate phenomena such as debris flows and pyroclastic flows requires use of the full mixture equations, which can simulate interaction of high-friction surge fronts with more-fluid debris that follows. Special numerical methods (described in the companion paper) are necessary to solve the full equations, but exact analytical solutions of simplified equations provide critical insight. An analytical solution for translational motion of a Coulomb mixture accelerating from rest and descending a uniform slope demonstrates that steady flow can occur only asymptotically. A solution for the asymptotic limit of steady flow in a rectangular channel explains why shear may be concentrated in narrow marginal bands that border a plug of translating debris. Solutions for static equilibrium of source areas describe conditions of incipient slope instability, and other static solutions show that nonuniform distributions of pore fluid pressure produce bluntly tapered vertical profiles at the margins of deposits. Simplified equations and solutions may apply in additional situations identified by a scaling analysis. Assessment of dimensionless scaling parameters also reveals that miniature laboratory experiments poorly simulate the dynamics of full-scale flows in which fluid effects are significant. Therefore large geophysical flows can exhibit dynamics not evident at laboratory scales.

Flow of variably fluidized granular masses across three-dimensional terrain: 1. Coulomb mixture theory

NASA Astrophysics Data System (ADS)

Iverson, Richard M.; Denlinger, Roger P.

2001-01-01

Rock avalanches, debris flows, and related phenomena consist of grain-fluid mixtures that move across three-dimensional terrain. In all these phenomena the same basic forces govern motion, but differing mixture compositions, initial conditions, and boundary conditions yield varied dynamics and deposits. To predict motion of diverse grain-fluid masses from initiation to deposition, we develop a depth-averaged, three-dimensional mathematical model that accounts explicitly for solid- and fluid-phase forces and interactions. Model input consists of initial conditions, path topography, basal and internal friction angles of solid grains, viscosity of pore fluid, mixture density, and a mixture diffusivity that controls pore pressure dissipation. Because these properties are constrained by independent measurements, the model requires little or no calibration and yields readily testable predictions. In the limit of vanishing Coulomb friction due to persistent high fluid pressure the model equations describe motion of viscous floods, and in the limit of vanishing fluid stress they describe one-phase granular avalanches. Analysis of intermediate phenomena such as debris flows and pyroclastic flows requires use of the full mixture equations, which can simulate interaction of high-friction surge fronts with more-fluid debris that follows. Special numerical methods (described in the companion paper) are necessary to solve the full equations, but exact analytical solutions of simplified equations provide critical insight. An analytical solution for translational motion of a Coulomb mixture accelerating from rest and descending a uniform slope demonstrates that steady flow can occur only asymptotically. A solution for the asymptotic limit of steady flow in a rectangular channel explains why shear may be concentrated in narrow marginal bands that border a plug of translating debris. Solutions for static equilibrium of source areas describe conditions of incipient slope instability, and other static solutions show that nonuniform distributions of pore fluid pressure produce bluntly tapered vertical profiles at the margins of deposits. Simplified equations and solutions may apply in additional situations identified by a scaling analysis. Assessment of dimensionless scaling parameters also reveals that miniature laboratory experiments poorly simulate the dynamics of full-scale flows in which fluid effects are significant. Therefore large geophysical flows can exhibit dynamics not evident at laboratory scales.

Adaptation to transient postural perturbations

NASA Technical Reports Server (NTRS)

Andres, Robert O.

1992-01-01

This research was first proposed in May, 1986, to focus on some of the problems encountered in the analysis of postural responses gathered from crewmembers. The ultimate driving force behind this line of research was the desire to treat, predict, or explain 'Space Adaptation Syndrome' (SAS) and hence circumvent any adverse effects of space motion sickness on crewmember performance. The aim of this project was to develop an easily implemented analysis of the transient responses to platform translation that can be elicited with a protocol designed to force sensorimotor reorganization, utilizing statistically reliable criterion measures. This report will present: (1) a summary of the activity that took place in each of the three funded years of the project; (2) discussion of experimental results and their implications for future research; and (3) a list of presentations and publications resulting from this project.

Mechanical properties of composite materials

NASA Technical Reports Server (NTRS)

Thornton, H. Richard; Cornwell, L. R.

1993-01-01

A composite material incorporates high strength, high modulus fibers in a matrix (polymer, metal, or ceramic). The fibers may be oriented in a manner to give varying in-plane properties (longitudinal, transverse-stress, strain, and modulus of elasticity). The lay-up of the composite laminates is such that a center line of symmetry and no bending moment exist through the thickness. The laminates are tabbed, with either aluminum or fiberglass, and are ready for tensile testing. The determination of the tensile properties of resin matrix composites, reinforced by continuous fibers, is outlined in ASTM standard D 3039, Tensile Properties of Oriented Fiber Composites. The tabbed flat tensile coupons are placed into the grips of a tensile machine and load-deformation curves plotted. The load-deformation data are translated into stress-strain curves for determination of mechanical properties (ultimate tensile strength and modulus of elasticity).

Standard Mutation Nomenclature in Molecular Diagnostics

PubMed Central

Ogino, Shuji; Gulley, Margaret L.; den Dunnen, Johan T.; Wilson, Robert B.

2007-01-01

To translate basic research findings into clinical practice, it is essential that information about mutations and variations in the human genome are communicated easily and unequivocally. Unfortunately, there has been much confusion regarding the description of genetic sequence variants. This is largely because research articles that first report novel sequence variants do not often use standard nomenclature, and the final genomic sequence is compiled over many separate entries. In this article, we discuss issues crucial to clear communication, using examples of genes that are commonly assayed in clinical laboratories. Although molecular diagnostics is a dynamic field, this should not inhibit the need for and movement toward consensus nomenclature for accurate reporting among laboratories. Our aim is to alert laboratory scientists and other health care professionals to the important issues and provide a foundation for further discussions that will ultimately lead to solutions. PMID:17251329

The metabolic footprint of aging in mice.

PubMed

Houtkooper, Riekelt H; Argmann, Carmen; Houten, Sander M; Cantó, Carles; Jeninga, Ellen H; Andreux, Pénélope A; Thomas, Charles; Doenlen, Raphaël; Schoonjans, Kristina; Auwerx, Johan

2011-01-01

Aging is characterized by a general decline in cellular function, which ultimately will affect whole body homeostasis. Although DNA damage and oxidative stress all contribute to aging, metabolic dysfunction is a common hallmark of aging at least in invertebrates. Since a comprehensive overview of metabolic changes in otherwise healthy aging mammals is lacking, we here compared metabolic parameters of young and 2 year old mice. We systemically integrated in vivo phenotyping with gene expression, biochemical analysis, and metabolomics, thereby identifying a distinguishing metabolic footprint of aging. Among the affected pathways in both liver and muscle we found glucose and fatty acid metabolism, and redox homeostasis. These alterations translated in decreased long chain acylcarnitines and increased free fatty acid levels and a marked reduction in various amino acids in the plasma of aged mice. As such, these metabolites serve as biomarkers for aging and healthspan.

Systems Approaches to Cancer Biology.

PubMed

Archer, Tenley C; Fertig, Elana J; Gosline, Sara J C; Hafner, Marc; Hughes, Shannon K; Joughin, Brian A; Meyer, Aaron S; Piccolo, Stephen R; Shajahan-Haq, Ayesha N

2016-12-01

Cancer systems biology aims to understand cancer as an integrated system of genes, proteins, networks, and interactions rather than an entity of isolated molecular and cellular components. The inaugural Systems Approaches to Cancer Biology Conference, cosponsored by the Association of Early Career Cancer Systems Biologists and the National Cancer Institute of the NIH, focused on the interdisciplinary field of cancer systems biology and the challenging cancer questions that are best addressed through the combination of experimental and computational analyses. Attendees found that elucidating the many molecular features of cancer inevitably reveals new forms of complexity and concluded that ensuring the reproducibility and impact of cancer systems biology studies will require widespread method and data sharing and, ultimately, the translation of important findings to the clinic. Cancer Res; 76(23); 6774-7. ©2016 AACR. ©2016 American Association for Cancer Research.

A Journey in Science: “Not Lost in Translation”

PubMed Central

Mak, Tak

2016-01-01

Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Tak Mak, PhD, Professor, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Princess Margaret Cancer Centre in Toronto. A visionary in the field of cancer, this is the story of Dr. Mak’s scientific journey. PMID:27819109

Engineering clinically relevant volumes of vascularized bone.

PubMed

Roux, Brianna M; Cheng, Ming-Huei; Brey, Eric M

2015-05-01

Vascularization remains one of the most important challenges that must be overcome for tissue engineering to be consistently implemented for reconstruction of large volume bone defects. An extensive vascular network is needed for transport of nutrients, waste and progenitor cells required for remodelling and repair. A variety of tissue engineering strategies have been investigated in an attempt to vascularize tissues, including those applying cells, soluble factor delivery strategies, novel design and optimization of bio-active materials, vascular assembly pre-implantation and surgical techniques. However, many of these strategies face substantial barriers that must be overcome prior to their ultimate translation into clinical application. In this review recent progress in engineering vascularized bone will be presented with an emphasis on clinical feasibility. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Precision medicine in chronic disease management: The multiple sclerosis BioScreen.

PubMed

Gourraud, Pierre-Antoine; Henry, Roland G; Cree, Bruce A C; Crane, Jason C; Lizee, Antoine; Olson, Marram P; Santaniello, Adam V; Datta, Esha; Zhu, Alyssa H; Bevan, Carolyn J; Gelfand, Jeffrey M; Graves, Jennifer S; Goodin, Douglas S; Green, Ari J; von Büdingen, H-Christian; Waubant, Emmanuelle; Zamvil, Scott S; Crabtree-Hartman, Elizabeth; Nelson, Sarah; Baranzini, Sergio E; Hauser, Stephen L

2014-11-01

We present a precision medicine application developed for multiple sclerosis (MS): the MS BioScreen. This new tool addresses the challenges of dynamic management of a complex chronic disease; the interaction of clinicians and patients with such a tool illustrates the extent to which translational digital medicine-that is, the application of information technology to medicine-has the potential to radically transform medical practice. We introduce 3 key evolutionary phases in displaying data to health care providers, patients, and researchers: visualization (accessing data), contextualization (understanding the data), and actionable interpretation (real-time use of the data to assist decision making). Together, these form the stepping stones that are expected to accelerate standardization of data across platforms, promote evidence-based medicine, support shared decision making, and ultimately lead to improved outcomes. © 2014 American Neurological Association.

Adrenomedullin and endocrine control of immune cells during pregnancy.

PubMed

Matson, Brooke C; Caron, Kathleen M

2014-09-01

The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal-fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies.

Molecular basis of physiological heart growth: fundamental concepts and new players

PubMed Central

Maillet, Marjorie; van Berlo, Jop H.; Molkentin, Jeffery D.

2015-01-01

The heart hypertrophies in response to developmental signals as well as increased workload. Although adult-onset hypertrophy can ultimately lead to disease, cardiac hypertrophy is not necessarily maladaptive and can even be beneficial. Progress has been made in our understanding of the structural and molecular characteristics of physiological cardiac hypertrophy, as well as of the endocrine effectors and associated signalling pathways that regulate it. Physiological hypertrophy is initiated by finite signals, which include growth hormones (such as thyroid hormone, insulin, insulin-like growth factor 1 and vascular endothelial growth factor) and mechanical forces that converge on a limited number of intracellular signalling pathways (such as PI3K, AKT, AMP-activated protein kinase and mTOR) to affect gene transcription, protein translation and metabolism. Harnessing adaptive signalling mediators to reinvigorate the diseased heart could have important medical ramifications. PMID:23258295

The translation of product concept to bone products: a partnership of therapeutic effectiveness and commercialization.

PubMed

Ratcliffe, Anthony

2011-12-01

The fields of tissue engineering and regenerative medicine have the capacity to substantially impact clinical care through the introduction of new products that can address unmet clinical needs, or significantly improve on present therapies. These products will be developed through the demonstration of therapeutic effectiveness, adequate safety, and meeting regulatory requirements. The technology used in the product will dictate the product development and manufacturing costs; the regulatory pathway; and the time taken to complete clinical trials, gain regulatory approval, and become commercialized. A comparison of the required investment of time and funds, with the potential revenue generated, allows for a determination of the likely commercialization opportunity. Ultimately, the long-term success of a product will be dependent on its clinical effectiveness and commercial viability. © Mary Ann Liebert, Inc.

Nitrite ion mitigates the formation of N-nitrosodimethylamine (NDMA) during chloramination of ranitidine.

PubMed

Seid, Mingizem Gashaw; Cho, Kangwoo; Lee, Changha; Park, Hyun-Mee; Hong, Seok Won

2018-08-15

Ranitidine (RNT) has been an important tertiary amine precursor of N-nitrosodimethylamine (NDMA) in chlorine-based water treatment, due to reaction with monochloramine (NH 2 Cl) with exceptionally high molar yields up to 90%. This study examined the effects of nitrite ions (NO 2 - ) on the kinetics of NDMA formation during the chloramination of RNT under variable concentrations of dissolved oxygen (DO, 0.7-7.5mg/L), RNT (5-30μM), NH 2 Cl (5-20mM), NO 2 - or NO 3 - (0-2mM) and pH (5.6-8.6). In the absence of the NO 2 - , the ultimate molar yield of NDMA after 6h of reaction was primarily influenced by [DO] and pH, while marginally affected by initial [RNT] and [NH 2 Cl]. A kinetic model, prepared in accordance with the reaction sequence of NDMA formation, suggested that the rate determining step was accelerated with increasing [NH 2 Cl] 0 , [DO], and pH. A Kinetic study together with ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometer (UPLC-Q-TOF MS) and gas chromatography (GC)/TOF MS analyses in parallel demonstrated that the nitrite ion inhibited the nucleophilic substitution of the terminal amine on NH 2 Cl, and reduced the pseudo-steady state concentration of N-peroxyl radicals, significantly decreasing the ultimate yields of NDMA. Copyright © 2018 Elsevier B.V. All rights reserved.

Volatile reservoirs below the surface of the Elysium region of Mars: Geomorphic evidence

NASA Technical Reports Server (NTRS)

Christiansen, Eric H.; Hopler, Jennifer A.

1987-01-01

The Elysium volcanic province contains a variety of geomorphic evidence for the existence of large volatile reservoirs of subsurface volatiles. Study of these landforms yields insight into the distribution and size of these reservoirs and how they interact with the surface environment and will ultimately place constraints on the geometry, constitution, origin, time of formation, and temporal evolution of these important components of the Martian crust. Three principal types of landforms appear to be related to subsurface volatile reservoirs in the Elysium region of Mars: small outflow channels; large lahars; and vast expanses of knobby terranes around the margins of the Elysium dome. The evidence provided by these landforms is internally consistent with the presence of a large relatively shallow volatile reservoir in the Elysium region. If the geologic features described are reliable indicators of subsurface volatiles, they imply that: volatile reservoirs lie relatively close to the surface and underlie millions of sq km in this region; there is no apparent latitudinal variation in the depth or thickness of the volatile reservoirs; the precursors of the knobby terranes are or were important volatile reservoirs; volatiles may be lost in a variety of ways from these reservoirs; and volatiles were incorporated in an easily eroded surficial deposit in the middle history of Mars. The ultimate origin of water in this reservoir is uncertain. A model to explain the preferential entrapment of volatiles into the region's surface materials may be required.

The development of blue ice moraines from englacial debris bands as detected by GPR, Mt Achernar, central Transantarctic Mountains, Antarctica

NASA Astrophysics Data System (ADS)

Kassab, C.; Lindback, K.; Pettersson, R.; Licht, K.; Graly, J. A.; Kaplan, M. R.

2016-12-01

Blue ice moraines cover a small percentage of Antarctica, but can contain a significant record of ice sheet dynamics and climate over multiple glacial cycles. Previous work has focused on the temporal and provenance record contained within these moraines and less on mechanisms by which such deposits form and their temporal evolution. In order to create a conceptual model of their formation, >25 km of ground penetrating radar transects at 25 and 100 MHz frequencies were collected at the Mt Achernar moraine adjacent to Law Glacier. Here, ice ablation causes debris bands to emerge and deliver sediment to the surface. Most transects were collected perpendicular to the ice-moraine margin, and extend from the actively flowing Law Glacier ice to a distance of 2 km into the moraine. The 25 and 100 MHz transects penetrate to a depth of 200 m and 60 m respectively and reveal a relatively complex internal stratigraphy. Closest to the ice-moraine margin, stratigraphy is not well resolved due to a high amount of clutter. Steeply dipping parallel reflections first emerge 400m away from the ice margin and dip toward Law Glacier. These reflections continue inwards to 1450m, where the reflections become more closely spaced. Hummocky topography and parallel ridge/trough topography dominate the geomorphic expression. The hummocky topography corresponds to the region where reflections are not well resolved. The ridges are interpreted to be debris bands that are emerging at the surface, similar to those along the margin of the Law Glacier where debris is newly emerging. The reflections in the GPR transects indicate that debris is transported from depth to the surface of the ice where it accumulates forming the Mt Achernar moraine. It appears that the various reflection patterns correspond to unique surface geomorphic expressions. The reflections also indicate that at least the first 2 km of debris rich buried ice in the moraine can be linked to the actively flowing Law Glacier. Understanding the formation of this moraine will assist with further interpretation of temporal and provenance data also collected at this site and ultimately contribute to the understanding of ice sheet dynamics and climate records contained within blue ice moraines.

Regional distribution of volcaniclastic layer and its implication for segmentation of the Nankai seismogenic zone

NASA Astrophysics Data System (ADS)

Sasaki, T.; Lim, J.; Higashi, M.; Park, J.

2010-12-01

The Nankai Trough is known as one of the best-suited convergent plate margins for studying accretionary prism growth as well as subduction zone earthquakes. Along the Nankai accretionary margin off southwest Japan, the Shikoku Basin which formed 26-15 Ma as backarc spreading in the Philippine Sea Plate is being subducted about 4 cm/year to the northwest. The Deep Sea Drilling Project (DSDP) and Ocean Drilling Program (ODP) penetrated the Nankai accretionary prism and the incoming sedimentary section along the Ashizuri and Muroto transects, off Shikoku Island. Also, Integrated Ocean Drilling Program (IODP), which represented just one part of a multi-stage project known as the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE) has been conducting drilling cruises now. IODP Expedition 322 in 2009, the coring was carried out at two drilling sites on the northern part of the Shikoku Basin in the subducting Philippine Sea plate. One of the major achievements of Expedition 322 is a discovery of late Miocene (10.2-7.6 Ma) tuffaceous and volcaniclastic sandstone layer (Underwood et al., IODP Prel. Rept. 322, 2009) that has not been previously recognized in the Nankai Trough. Based on age and volcanic sand content analysis, these volcaniclastic layers were unique to the Shikoku Basin off Kii Peninsula. The closest source of this volcanic layer was supposed to be the Izu-Bonin arc. Subducted sediments ultimately affect subduction zone geochemistry, thermal structure, and seismogenesis. High porosity of the volcaniclastic sandstone layer suggests the transportation of fluid to the subduction zone, it might affect the initiation and evolution of the decollement zone or plate boundary fault in the Nankai Trough. We interpreted single channel and multichannel seismic reflection profiles that have been acquired in the Nankai Trough margin by Japan Agency for Marine-Earth Science and Technology (JAMSTEC) since the year of 1997. We tried to map the major seismic layers such as volcaniclastic layer, volcanic ash layer and turbidite layers which were found at drilling sites in the IODP Expedition 322 in the northern Shikoku Basin. As a result, we recognized that these prominent seismic layers are widely distributed in the northern Shikoku Basin. In this talk, we will show specific seismic layers directly connecting to the decollement at the Nankai Trough axis, and discuss its implications for subduction processes in the Nankai Trough margin.

Drawing disability in Japanese manga: visual politics, embodied masculinity, and wheelchair basketball in Inoue Takehiko's REAL.

PubMed

Wood, Andrea

2013-12-01

This work explores disability in the cultural context of contemporary Japanese comics. In contrast to Western comics, Japanese manga have permeated the social fabric of Japan to the extent that vast numbers of people read manga on a daily basis. It has, in fact, become such a popular medium for visual communication that the Japanese government and education systems utilize manga as a social acculturation and teaching tool. This multibillion dollar industry is incredibly diverse, and one particularly popular genre is sports manga. However, Inoue Takehiko's award-winning manga series REAL departs from more conventional sports manga, which typically focus on able-bodied characters with sometimes exaggerated superhuman physical abilities, by adopting a more realistic approach to the world of wheelchair basketball and the people who play it. At the same time REAL explores cultural attitudes toward disability in Japanese culture-where disability is at times rendered "invisible" either through accessibility problems or lingering associations of disability and shame. It is therefore extremely significant that manga, a visual medium, is rendering disability visible-the ultimate movement from margin to center. REAL devotes considerable attention to realistically illustrating the lived experiences of its characters both on and off the court. Consequently, the series not only educates readers about wheelchair basketball but also provides compelling insight into Japanese cultural notions about masculinity, family, responsibility, and identity. The basketball players-at first marginalized by their disability-join together in the unity of a sport typically characterized by its "abledness."

Jurassic rifting at the Eurasian Tethys margin: Geochemical and geochronological constraints from granitoids of North Makran, southeastern Iran

NASA Astrophysics Data System (ADS)

Hunziker, Daniela; Burg, Jean-Pierre; Bouilhol, Pierre; von Quadt, Albrecht

2015-03-01

This study focuses on an east-west trending belt of granitic to intermediate intrusions and their volcanic cover in the northern Dur Kan Complex, a continental slice outcropping to the north of the exposed Makran accretionary wedge in southeastern Iran. Field observations, petrographic descriptions, trace element, and isotope analyses combined with U-Pb zircon geochronology are presented to determine the time frame of magmatism and tectonic setting during the formation of these rocks. Results document three magmatic episodes with different melt sources for (1) granites, (2) a diorite-trondhjemite-plagiogranite sequence, and (3) diabases and lavas. Granites, dated at 170-175 Ma, represent crystallized melt with a strong continental isotopic contribution. The diorite-trondhjemite-plagiogranite sequence is 165-153 Ma old and derives from a mantle magma source with minor continental contribution. East-west trending diabase dikes and bodies intruded the granitoids, which were eroded and then covered by Valanginian (140-133 Ma) alkaline lavas and sediments. Alkaline dikes and lavas have a mantle isotopic composition. Temporal correlation with plutonites of the Sanandaj-Sirjan Zone to the northwest defines a narrow, NW-SE striking and nearly 2000 km long belt of Jurassic intrusions. The increasing mantle influence in the magma sources is explained by thinning of continental lithosphere and related mantle upwelling/decompression melting. Accordingly, the formation of the studied igneous rocks is related to the extension of the Iranian continental margin, which ultimately led to the formation of the Tethys-related North Makran Ophiolites.

Regulation of breeding behavior: do energy-demanding periods induce a change in prolactin or corticosterone baseline levels in the common tern (Sterna hirundo)?

PubMed

Riechert, Juliane; Chastel, Olivier; Becker, Peter H

2014-01-01

Hormones are involved in reproductive decisions, linking environmental cues and body condition and adapting behavior. Mass loss is often accompanied by decreased prolactin and increased corticosterone concentrations, influencing incubation and brooding behavior and ultimately triggering nest desertion. Using blood-sucking bugs (Dipetalogaster maxima), we measured baseline prolactin, corticosterone, and ketone body values in incubating common terns (Sterna hirundo) between 2006 and 2009 during energy-demanding periods: 50 pairs were sampled hungry (after an incubation bout) and again fed (after foraging). In a second approach, we sampled 57 other pairs (experienced and inexperienced birds) three times over their individual breeding period, because reproduction, especially chick rearing, is a very energy-demanding process. In line with the common physiological pattern of fasting, we found significantly lower baseline prolactin values in hungry terns, which were negatively related to mass loss over the incubation bout, whereas corticosterone and ketone body levels were marginally increased. Compared to that in the incubation phase, the prolactin level dropped after hatching of chicks in inexperienced birds, perhaps indicating lower parental expenditure. Corticosterone, on the other hand, increased after hatching in males, probably linked to higher foraging activity, as males mainly deliver food during the first days. These energy-demanding periods clearly influenced hormones and ketone bodies, maybe reinforced by the low energy margin of this small seabird species, but energy reserves were not depleted to a level affecting behavior or reproductive success.