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Find video protocols related to scientific articles indexed in Pubmed.
Medication-Related Fall Incidents in an Older, Ambulant Population: The B-PROOF Study.
Drugs Aging
PUBLISHED: 11-16-2014
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Medication use is a potentially modifiable risk factor for falling; psychotropic and cardiovascular drugs have been indicated as main drug groups that increase fall risk. However, evidence is mainly based on studies that recorded falls retrospectively and/or did not determine medication use at the time of the fall. Therefore, we investigated the associations indicated in the literature between medication use and falls, using prospectively recorded falls and medication use determined at the time of the fall.
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What Women Think: Cancer Causal Attributions in a Diverse Sample of Women.
J Psychosoc Oncol
PUBLISHED: 11-15-2014
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Abstract Women hold diverse beliefs about cancer etiology, potentially affecting their use of cancer preventive behaviors. To date, research has greatly focused on the causal attributions cancer patients and survivors hold about cancer, and studies have been conducted primarily with White participants. Less is known about causal attributions held by women with and without a family history of cancer from a diverse community sample. This study sought to identify cancer causal attributions of women with and without a family history of cancer, and explore its relation to socio-cultural factors. Diverse women (60% African-American) recruited at an urban, safety-net women's health clinic (N = 471) reported factors they believed cause cancer. Responses were coded into nine attributions and analyzed using chi-squares and logistic regressions. Lifestyle-choices (63%), genetics/heredity (34%), and environmental-exposures (19%) were the top causal attributions identified. Women without a family history of cancer were more likely to identify genetics/heredity as an attribution for cancer than women with a history of cancer in their families. Women who identified as White, who had a higher educational attainment, and had commercial insurance were more likely to report genetics/heredity as a causal attribution for cancer. These findings suggest that socio-cultural factors may play a role in the causal attributions individuals make about cancer, which can, in turn, inform cancer awareness and prevention messages.
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Recent developments in neurofibromatoses and RASopathies: Management, diagnosis and current and future therapeutic avenues.
Am. J. Med. Genet. A
PUBLISHED: 11-14-2014
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Neurofibromatosis type 1 (NF1) was the first RASopathy and is now one of many RASopathies that are caused by germline mutations in genes that encode components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Their common underlying pathogenetic etiology causes significant overlap in phenotypic features which includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium "Recent Developments in Neurofibromatoses (NF) and RASopathies: Management, Diagnosis and Current and Future Therapeutic Avenues" chronicle this timely and topical clinical translational research symposium. The overarching goal was to bring together clinicians, basic scientists, physician-scientists, advocate leaders, trainees, students and individuals with Ras pathway syndromes to discuss the most state-of-the-art basic science and clinical issues in an effort to spark collaborations directed towards the best practices and therapies for individuals with RASopathies. © 2014 Wiley Periodicals, Inc.
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Building the gateway to success: An appraisal of progress in reaching underserved families and reducing racial disparities in school-based mental health.
Psychol Serv
PUBLISHED: 11-11-2014
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School-based mental health (SBMH) services hold the promise of reducing barriers to care among underserved children and families in need, which can in turn reduce racial disparities in care. Yet, questions remain about the potential of SBMH for equitably reaching diverse communities. In particular, reaching Asian American youth in SBMH may remain a challenge even compared with other immigrant and ethnic minority groups, such as Latinos. This article describes the development and evaluates the service capacity of a SBMH platform in a medium-sized public school district serving predominantly low-income Latino and Asian American families. Service capacity was built through the creation and coordination of a system of community partnerships. Analyses of needs assessment and service referral and utilization patterns revealed no significant racial/ethnic differences in overall rates of mental health need between Latino and Asian American students; yet, Asian Americans were underrepresented in referrals to SBMH. However, once referred to care, there was no difference in the likelihood that Asian American and Latino students received treatment. Although there was an increase in capacity to link students to care, work remains to improve processes of identification to reduce unmet need across diverse groups. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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Decomposing Racial Disparities in Prison and Drug Treatment Commitments for Criminal Offenders in California.
J Legal Stud
PUBLISHED: 11-11-2014
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Blacks convicted of drug-related offenses in the U.S. have higher prison-commitment rates than Whites. Studies have been largely unsuccessful in explaining these disparities. This study uses administrative data from a random sample of individuals arrested for drug offenses in California to examine this issue. We use a decomposition model to estimate whether Black-White disparities in commitments to prison or diversions to drug treatment are attributable to differences in the characteristics of criminal cases and whether case characteristics are weighed differently by race. We also examine whether the influence of case characteristics changes after California implemented Proposition 36, which was a mandatory prison diversion program for eligible drug offenders. Our results suggest that Black-White differences in prison commitments are fully explained by criminal case characteristics, but that a significant portion of the differences in treatment diversions remain unexplained. The unexplained variation in drug treatment also does not change after Proposition 36. These findings suggest that case characteristics play a larger role in explaining prison commitments for drug offenders than the discretion of prosecutors and judges. By contrast, diversion to drug treatment appears to be driven more by the discretion of court officials and Black-White disparities remain prominent.
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Granulomatous changes associated with pigmented purpuric dermatosis.
Cutis
PUBLISHED: 11-06-2014
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Granulomatous pigmented purpuric dermatosis (GPPD) is a rare entity with few cases reported in the literature. We report 3 cases of pigmented purpuric dermatosis (PPD) with granulomatous features in a 9-year-old boy, a 49-year-old woman, and a 75-year-old woman. We also review the literature on PPDs with granulomatous features, including histopathologic features and disease associations. Most of the cases we reviewed described granulomas superimposed on classic changes of PPD. We also identify a new variant of GPPD in 2 of our patients who presented with granulomatous infiltrates in the mid to deep dermis. Granulomatous PPD does not appear to have a consistent association with underlying disease; notably, hyperlipidemia was seen in 7 cases we reviewed.
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Changes in tar yields and cigarette design in samples of Chinese cigarettes, 2009 and 2012.
Tob Control
PUBLISHED: 10-30-2014
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China is home to the greatest number of smokers as well as the greatest number of smoking-related deaths. An active and growing market of cigarettes marketed as 'light' or 'low tar' may keep health-concerned smokers from quitting, wrongly believing that such brands are less harmful.
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Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section.
Cochrane Database Syst Rev
PUBLISHED: 10-29-2014
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The single most important risk factor for postpartum maternal infection is cesarean section. Although guidelines endorse the use of prophylactic antibiotics for women undergoing cesarean section, there is not uniform implementation of this recommendation. This is an update of a Cochrane review first published in 1995 and last updated in 2010.
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Prenatal versus postnatal repair procedures for spina bifida for improving infant and maternal outcomes.
Cochrane Database Syst Rev
PUBLISHED: 10-29-2014
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Spina bifida is a fetal neural tube defect (NTD), which may be diagnosed in utero and is compatible with life postnatally, albeit often with significant disability and morbidity. Although postnatal repair is possible, with increasing in utero diagnosis with ultrasound, the condition has been treated during pregnancy (prenatal repair) with the aim of decreased morbidity for the child. The procedure that is performed during pregnancy does have potential morbidities for the mother, as it involves maternal surgery to access the fetus.
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Toxic metal and nicotine content of cigarettes sold in China, 2009 and 2012.
Tob Control
PUBLISHED: 10-23-2014
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Metals of primary health concern can accumulate in the tobacco plant and contribute to smokers' exposures to carcinogens, a significant cause of the millions of smoking-related deaths in China each year. These exposures are due to the smoker's addiction to nicotine.
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The KinFact Intervention - A Randomized Controlled Trial to Increase Family Communication About Cancer History.
J Womens Health (Larchmt)
PUBLISHED: 10-17-2014
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Abstract Background: Knowing family history is important for understanding cancer risk, yet communication within families is suboptimal. Providing strategies to enhance communication may be useful.
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Effects of climate change on the toxicity of soils polluted by metal mine wastes to Enchytraeus crypticus.
Environ. Toxicol. Chem.
PUBLISHED: 10-09-2014
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The present study aimed to assess the effects of climate change on the toxicity of metal-polluted soils. Bioassays with Enchytraeus crypticus were performed in soils polluted by mine wastes (mine tailing, forest and watercourse) and under different combinations of temperature (20 and 25 °C) and soil moisture content (50 and 30% of the soil water holding capacity). Survival and reproduction were determined as endpoints. No effect was observed on survival (average survival ?80%). Reproduction was the most sensitive endpoint, and it was reduced between 65 and 98% compared to the control when exposed to the watercourse soil (lower pH, higher salinity and higher available metal(loid)s concentrations). In this soil, EC50 and EC10 significantly decreased with decreasing soil moisture content. In general, the worst case scenario was the driest soil, but the toxicity under a climate change scenario differed among soil types in relation to soil properties (e.g. pH, salinity) and available metal(loid)s concentrations. This article is protected by copyright. All rights reserved.
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Effect of temperature on the intrinsic flexibility of DNA and its interaction with architectural proteins.
Biochemistry
PUBLISHED: 10-07-2014
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The helical structure of double-stranded DNA is destabilized by increasing temperature. Above a critical temperature (the melting temperature), the two strands in duplex DNA become fully separated. Below this temperature, the structural effects are localized. Using tethered particle motion in a temperature-controlled sample chamber, we systematically investigated the effect of increasing temperature on DNA structure and the interplay between this effect and protein binding. Our measurements revealed that (1) increasing temperature enhances DNA flexibility, effectively leading to more compact folding of the double-stranded DNA chain, and (2) temperature differentially affects different types of DNA-bending chromatin proteins from mesophilic and thermophilic organisms. Thus, our findings aid in understanding genome organization in organisms thriving at moderate as well as extreme temperatures. Moreover, our results underscore the importance of carefully controlling and measuring temperature in single-molecule DNA (micromanipulation) experiments.
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The quantitation of replication-competent HIV-1 in populations of resting CD4+ T cells.
J. Virol.
PUBLISHED: 09-24-2014
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Central memory (TCM) CD4(+) T cells are the principal reservoir of latent HIV-1 infection that persists despite durable, successful antiretroviral therapy (ART). In a study that measured HIV DNA in 34 patients and replication-competent HIV in four patients, pools of resting and activated transitional memory (TTM) CD4(+) T cells were found to be a reservoir for HIV infection. As defective viruses account for the majority of integrated HIV DNA and do not reflect the actual frequency of latent, replication-competent proviral infection, we assessed the specific contribution of resting TTM cells to latent HIV infection. We measured the frequency of replication-competent HIV in purified resting memory cell subpopulations by a limiting dilution, quantitative viral outgrowth assay (QVOA). HIV was routinely detected within the resting central memory compartment, but was infrequently detected within the resting TTM compartment. These observations suggest that prolonged ART may limit persistent latent infection in the TTM compartment. Our results confirm the importance of latent infection within the TCM compartment, and again focus attention on these cells as the most important latent viral reservoir. While proliferation may drive expansion of detectable viral genomes in cells, the frequency of replication-competent HIV must be carefully assessed. Latent infection appears to wane within the transitional memory compartment in patients who have sustained successful viral suppression via ART, or were treated very early in infection.
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Vitamin A metabolism and mucosal immune function are distinct between BALB/c and C57BL/6 mice.
Eur. J. Immunol.
PUBLISHED: 09-23-2014
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The vitamin A metabolite retinoic acid (RA) has been reported to suppress Th1 responses and enhance Th2 responses. Here, we investigated whether differences in vitamin A metabolism could underlie the differences between C57BL/6 and BALB/c mice, which are reportedly seen as Th1 and Th2 responders, respectively. BALB/c mice were shown to have higher intestinal epithelial expression of RALDH1 (where RALDH is retinaldehyde dehydrogenase), and, consequently, higher RALDH activity in MLN-DCs, leading to an increased ability to induce IgA class switching in B cells. Furthermore, within BALB/c mice, induction of IgA secretion as well as increased accumulation of regulatory T cells (Treg) in the intestinal lamina propria was observed. Additionally, as BALB/c mice are more resistant to dextran sulphate sodium (DSS) induced colitis, mice that lacked vitamin A in their diet had a more severe form of DSS-induced colitis compared to control mice. Therefore, the level of RA production and consequently the degree of RA-mediated signaling is crucial for the efficiency of the mucosal immune system.
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Pick-up of early visual information to guide kinetics and kinematics within a group of highly skilled baseball batters.
Percept Mot Skills
PUBLISHED: 09-22-2014
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Summary.-This pilot study integrated sport expertise and biomechanics methodologies within a baseball batting task. Purpose was to examine differences within a highly skilled group of baseball batters to use visual information to guide weight transfer and bat movements. One batter who played at Major League Baseball (MLB) level was compared to five batters who played at Australian Baseball League (ABL) level in a case-control design. Batters faced pitchers in a simulated competition and attempted to hit pitches, while vision was temporally occluded during ball flight or not occluded. Time of weight transfer (kinetics), as well as bat downswing initiation and duration (kinematics) from the point of ball release, were compared between the MLB batter and ABL batters. Results indicated that the MLB batter coordinated his striking pattern by completing his weight transfer earlier than the ABL batters. His bat downswing was also initiated earlier than some ABL batters, but there was no difference in duration of bat downswing between batters. All batters initiated bat downswing prior to completion of weight transfer. Understanding of motor expertise is furthered using a novel methodology.
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Preventing pre-eclampsia - are dietary factors the key?
BMC Med
PUBLISHED: 09-09-2014
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Pre-eclampsia is a common pregnancy related condition, which contributes significantly both to maternal and perinatal morbidity and mortality. The precise pathophysiology of pre-eclampsia is uncertain, and the development of effective preventive strategies remains elusive. Schoenaker and colleagues conducted a systematic review and meta-analysis of observational studies reporting dietary intake and dietary patterns. The findings indicated that women with a low dietary calcium intake were more likely to be diagnosed with gestational hypertension, while there was a suggestion (although not statistically significant) of a beneficial effect of a diet rich in fruits and vegetables on risk of pre-eclampsia. This is in contrast to the findings of systematic reviews and meta-analyses of randomised trials in pregnancy evaluating calcium supplementation and anti-oxidant vitamin C and E supplementation. The validity of any systematic review is reliant on both the underlying methodology and the quality of each of the included studies; the review by Schoenaker and colleagues is limited by the observational nature of the included studies.Please see related article: http://www.biomedcentral.com/1741-7015/12/157/abstract.
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Defining the role of common variation in the genomic and biological architecture of adult human height.
Andrew R Wood, Tonu Esko, Jian Yang, Sailaja Vedantam, Tune H Pers, Stefan Gustafsson, Audrey Y Chu, Karol Estrada, Jian'an Luan, Zoltan Kutalik, Najaf Amin, Martin L Buchkovich, Damien C Croteau-Chonka, Felix R Day, Yanan Duan, Tove Fall, Rudolf Fehrmann, Teresa Ferreira, Anne U Jackson, Juha Karjalainen, Ken Sin Lo, Adam E Locke, Reedik Mägi, Evelin Mihailov, Eleonora Porcu, Joshua C Randall, André Scherag, Anna A E Vinkhuyzen, Harm-Jan Westra, Thomas W Winkler, Tsegaselassie Workalemahu, Jing Hua Zhao, Devin Absher, Eva Albrecht, Denise Anderson, Jeffrey Baron, Marian Beekman, Ayse Demirkan, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Ross M Fraser, Anuj Goel, Jian Gong, Anne E Justice, Stavroula Kanoni, Marcus E Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Julian C Lui, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Michael A Nalls, Dale R Nyholt, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Inga Prokopenko, Janina S Ried, Stephan Ripke, Dmitry Shungin, Alena Stančáková, Rona J Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Uzma Afzal, Johan Arnlöv, Gillian M Arscott, Stefania Bandinelli, Amy Barrett, Claire Bellis, Amanda J Bennett, Christian Berne, Matthias Blüher, Jennifer L Bolton, Yvonne Böttcher, Heather A Boyd, Marcel Bruinenberg, Brendan M Buckley, Steven Buyske, Ida H Caspersen, Peter S Chines, Robert Clarke, Simone Claudi-Boehm, Matthew Cooper, E Warwick Daw, Pim A de Jong, Joris Deelen, Graciela Delgado, Josh C Denny, Rosalie Dhonukshe-Rutten, Maria Dimitriou, Alex S F Doney, Marcus Dörr, Niina Eklund, Elodie Eury, Lasse Folkersen, Melissa E Garcia, Frank Geller, Vilmantas Giedraitis, Alan S Go, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Henrik Grönberg, Lisette C P G M de Groot, Christopher J Groves, Jeffrey Haessler, Per Hall, Toomas Haller, Göran Hallmans, Anke Hannemann, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Nancy L Heard-Costa, Quinta Helmer, Gibran Hemani, Anjali K Henders, Hans L Hillege, Mark A Hlatky, Wolfgang Hoffmann, Per Hoffmann, Oddgeir Holmen, Jeanine J Houwing-Duistermaat, Thomas Illig, Aaron Isaacs, Alan L James, Janina Jeff, Berit Johansen, Asa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Juhani Junttila, Abel N Kho, Leena Kinnunen, Norman Klopp, Thomas Kocher, Wolfgang Kratzer, Peter Lichtner, Lars Lind, Jaana Lindström, Stéphane Lobbens, Mattias Lorentzon, Yingchang Lu, Valeriya Lyssenko, Patrik K E Magnusson, Anubha Mahajan, Marc Maillard, Wendy L McArdle, Colin A McKenzie, Stela McLachlan, Paul J McLaren, Cristina Menni, Sigrun Merger, Lili Milani, Alireza Moayyeri, Keri L Monda, Mario A Morken, Gabriele Müller, Martina Müller-Nurasyid, Arthur W Musk, Narisu Narisu, Matthias Nauck, Ilja M Nolte, Markus M Nöthen, Laticia Oozageer, Stefan Pilz, Nigel W Rayner, Frida Renstrom, Neil R Robertson, Lynda M Rose, Ronan Roussel, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R Schumacher, Heribert Schunkert, Robert A Scott, Joban Sehmi, Thomas Seufferlein, Jianxin Shi, Karri Silventoinen, Johannes H Smit, Albert Vernon Smith, Joanna Smolonska, Alice V Stanton, Kathleen Stirrups, David J Stott, Heather M Stringham, Johan Sundström, Morris A Swertz, Ann-Christine Syvänen, Bamidele O Tayo, Gudmar Thorleifsson, Jonathan P Tyrer, Suzanne van Dijk, Natasja M van Schoor, Nathalie van der Velde, Diana van Heemst, Floor V A van Oort, Sita H Vermeulen, Niek Verweij, Judith M Vonk, Lindsay L Waite, Melanie Waldenberger, Roman Wennauer, Lynne R Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Alan F Wright, Qunyuan Zhang, Dominique Arveiler, Stephan J L Bakker, John Beilby, Richard N Bergman, Sven Bergmann, Reiner Biffar, John Blangero, Dorret I Boomsma, Stefan R Bornstein, Pascal Bovet, Paolo Brambilla, Morris J Brown, Harry Campbell, Mark J Caulfield, Aravinda Chakravarti, Rory Collins, Francis S Collins, Dana C Crawford, L Adrienne Cupples, John Danesh, Ulf de Faire, Hester M den Ruijter, Raimund Erbel, Jeanette Erdmann, Johan G Eriksson, Martin Farrall, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G Forouhi, Terrence Forrester, Ron T Gansevoort, Pablo V Gejman, Christian Gieger, Alain Golay, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, David W Haas, Alistair S Hall, Tamara B Harris, Andrew T Hattersley, Andrew C Heath, Christian Hengstenberg, Andrew A Hicks, Lucia A Hindorff, Aroon D Hingorani, Albert Hofman, G Kees Hovingh, Steve E Humphries, Steven C Hunt, Elina Hyppönen, Kevin B Jacobs, Marjo-Riitta Järvelin, Pekka Jousilahti, Antti M Jula, Jaakko Kaprio, John J P Kastelein, Manfred Kayser, Frank Kee, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Jaspal S Kooner, Charles Kooperberg, Seppo Koskinen, Peter Kovacs, Aldi T Kraja, Meena Kumari, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Sara Lupoli, Pamela A F Madden, Satu Mannisto, Paolo Manunta, André Marette, Tara C Matise, Barbara McKnight, Thomas Meitinger, Frans L Moll, Grant W Montgomery, Andrew D Morris, Andrew P Morris, Jeffrey C Murray, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Willem H Ouwehand, Gerard Pasterkamp, Annette Peters, Peter P Pramstaller, Jackie F Price, Lu Qi, Olli T Raitakari, Tuomo Rankinen, D C Rao, Treva K Rice, Marylyn Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Peter E H Schwarz, Sylvain Sebert, Peter Sever, Alan R Shuldiner, Juha Sinisalo, Valgerdur Steinthorsdottir, Ronald P Stolk, Jean-Claude Tardif, Anke Tönjes, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, , Philippe Amouyel, Folkert W Asselbergs, Themistocles L Assimes, Murielle Bochud, Bernhard O Boehm, Eric Boerwinkle, Erwin P Bottinger, Claude Bouchard, Stéphane Cauchi, John C Chambers, Stephen J Chanock, Richard S Cooper, Paul I W de Bakker, George Dedoussis, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Leif C Groop, Christopher A Haiman, Anders Hamsten, M Geoffrey Hayes, Jennie Hui, David J Hunter, Kristian Hveem, J Wouter Jukema, Robert C Kaplan, Mika Kivimäki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G Martin, Winfried März, Mads Melbye, Susanne Moebus, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin N A Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Joseph E Powell, Chris Power, Thomas Quertermous, Rainer Rauramaa, Eva Reinmaa, Paul M Ridker, Fernando Rivadeneira, Jerome I Rotter, Timo E Saaristo, Danish Saleheen, David Schlessinger, P Eline Slagboom, Harold Snieder, Tim D Spector, Konstantin Strauch, Michael Stumvoll, Jaakko Tuomilehto, Matti Uusitupa, Pim van der Harst, Henry Völzke, Mark Walker, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, James F Wilson, Pieter Zanen, Panos Deloukas, Iris M Heid, Cecilia M Lindgren, Karen L Mohlke, Elizabeth K Speliotes, Unnur Thorsteinsdottir, Inês Barroso, Caroline S Fox, Kari E North, David P Strachan, Jacques S Beckmann, Sonja I Berndt, Michael Boehnke, Ingrid B Borecki, Mark I McCarthy, Andres Metspalu, Kari Stefansson, André G Uitterlinden, Cornelia M van Duijn, Lude Franke, Cristen J Willer, Alkes L Price, Guillaume Lettre, Ruth J F Loos, Michael N Weedon, Erik Ingelsson, Jeffrey R O'Connell, Gonçalo R Abecasis, Daniel I Chasman, Michael E Goddard, Peter M Visscher, Joel N Hirschhorn, Timothy M Frayling.
Nat. Genet.
PUBLISHED: 08-29-2014
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Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ?2,000, ?3,700 and ?9,500 SNPs explained ?21%, ?24% and ?29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/?-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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Factors that drive the gap in diabetes rates between Aboriginal and non-Aboriginal people in non-remote NSW.
Aust N Z J Public Health
PUBLISHED: 08-28-2014
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To identify factors underpinning the gap in diabetes rates between Aboriginal and non-Aboriginal people in non-remote NSW. This will indicate appropriate target areas for policy and for monitoring progress towards reducing the gap.
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Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation.
Elife
PUBLISHED: 08-21-2014
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Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8(+) T cells and MHC-II-dependent anergy of CD4(+) T cells. Here, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.
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CD30 positive atypical lymphocytes in perniosis: a potential histopathologic pitfall in a benign condition.
Am J Dermatopathol
PUBLISHED: 07-30-2014
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In classical clinical perniosis (chilblains), the presence of atypical lymphocytes with immunohistochemical staining positive for CD30 is unusual and rarely reported. Here we report 2 cases of clinical perniosis, one in a 16-year-old girl and another in a 67-year-old woman. The biopsies revealed lymphocytic infiltrates, papillary dermal edema, and atypical cells highlighted with a CD30 immunohistochemical stain. Our cases demonstrate the importance of clinicopathologic correlation in the assessment of CD30 positive lymphocytes in benign nonneoplastic conditions. Dermatopathologists must be aware of this potential histologic pattern in perniosis to prevent misdiagnosis and overtreatment of this condition.
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Surgical techniques for uterine incision and uterine closure at the time of caesarean section.
Cochrane Database Syst Rev
PUBLISHED: 07-23-2014
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Caesarean section is a common operation. Techniques vary depending on both the clinical situation and the preferences of the operator.
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Non-linear associations between serum 25-OH vitamin D and indices of arterial stiffness and arteriosclerosis in an older population.
Age Ageing
PUBLISHED: 07-21-2014
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several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population.
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The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial.
BMC Med
PUBLISHED: 07-18-2014
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Overweight and obesity during pregnancy represents a considerable health burden. While research has focused on interventions to limit gestational weight gain, there is little information describing their impact on neonatal health. Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese.
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Biologic differences between peripheral and transition zone prostate cancer.
Prostate
PUBLISHED: 07-08-2014
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Prostate cancer arises in the transition zone (TZ) in approximately 20-25% of cases. Modern biopsy and surveillance protocols, and advances in prostate cancer imaging, have renewed interest in TZ prostate cancers. We compared TZ and PZ prostate cancer to determine if cancer location is independently associated with better outcomes.
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Associations between medication use and homocysteine levels in an older population, and potential mediation by vitamin B12 and folate: data from the B-PROOF Study.
Drugs Aging
PUBLISHED: 07-05-2014
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Elevated homocysteine levels are a risk indicator for cardiovascular disease, fractures and cognitive decline. Previous studies indicated associations between homocysteine levels and medication use, including antihypertensive, lipid-lowering and antidiabetic medication. However, results were often contradictory and inconclusive. Our objective was to study the associations established previously in more detail by sub-classifying medication groups, and investigate the potential mediating role of vitamin B12 and folate status.
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Nuclear KLLN expression associates with improved relapse-free survival for prostate carcinoma.
Endocr. Relat. Cancer
PUBLISHED: 06-29-2014
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Men with organ-confined prostate cancer (CaP) are often treated with radical prostatectomy. Despite similar postoperative characteristics, a significant proportion of men with an intermediate risk of progression experience prostate-specific antigen (PSA)-defined failure, while others have relapse-free survival (RFS). Additional prognostic markers are needed to predict the outcome of these patients. KLLN is a transcription factor that regulates the cell cycle and induces apoptosis in cancer cells. We have shown that KLLN is an androgen-regulated gene and that loss of KLLN expression in primary CaP is associated with high Gleason score. In this retrospective study, we evaluated KLLN expression in the high-grade malignancy components from 109 men with intermediate risk CaP. Patients with nuclear KLLN-negative tumors had significantly higher preoperative serum PSA levels (12.24±2.37?ng/ml) and larger tumor volumes (4.61±0.71?cm(3)) compared with nuclear KLLN-positive patients (8.35±2.45?ng/ml, P=0.03, and 2.66±0.51?cm(3), P<0.0001, respectively). None of the nuclear KLLN-positive tumors had capsular penetration, whereas 34% of nuclear KLLN-negative tumors (P=0.004) had capsular penetration. Maintaining KLLN expression in tumor nuclei, but not in cytoplasm or stroma, associated with improved RFS after surgery (P=0.002). Only 7% of patients with nuclear KLLN-positive tumors had tumor recurrence, while 60% of patients in the KLLN-negative group developed PSA-defined failure with median relapse time of 6.6 months (P=0.0003). Our data suggest that KLLN expression may be used as a prognostic marker to predict outcome for intermediate risk patients, which could provide useful information for postoperative management.
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"Listening to the silence quietly": investigating the value of cultural immersion and remote experiential learning in preparing midwifery students for clinical practice.
BMC Res Notes
PUBLISHED: 05-16-2014
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Cultural immersion programs are increasingly offered to medical and health science students in an effort to provide experiential learning opportunities that focus on 'the self' as well as 'the other'. Immersion programs encourage self-reflection on attitudes towards cultural differences, provide opportunities to build relationships and work with community members, and allow students to apply knowledge and skills learned in training programs in a supervised practice setting. The aim of this paper is to describe midwifery students' reflections on a remote Aboriginal clinical placement that has been offered at a Western Australian university since 2010.
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Comparison of contemporaneous EQ-5D and SF-6D responses using scoring algorithms derived from similar valuation exercises.
Value Health
PUBLISHED: 05-14-2014
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Poor agreement between preference-based health-related quality-of-life instruments has been widely reported across patient and community-based samples. This study compares index scores generated from contemporaneous EQ-5D (3-level version) and SF-6D (SF-36 version) responses using scoring algorithms derived from independently-conducted Australian population-representative discrete choice experiments (DCEs), providing the first comparative analysis of health state valuations using the same method of valuation across the full value sets.
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The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial.
BMC Med
PUBLISHED: 04-24-2014
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Overweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity.
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Nobody's perfect: a qualitative examination of African American maternal caregivers' and their adolescent girls' perceptions of body image.
Body Image
PUBLISHED: 04-22-2014
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Using semi-structured interviews, we explored African American maternal caregivers' and their adolescent girls' (N=25 dyads) perceptions about the adolescent's body using Grounded Theory. Caregivers and adolescent girls (Mage=13.42) were asked what the adolescent girls liked most/least about their bodies and how peers and media may affect adolescent girls' perceptions. While some adolescent girls reported overall body satisfaction, others described features they would like to change. Belief in God, body acceptance, and appreciation for average/moderate features helped the adolescent girls maintain their positive body image. The body-related messages that adolescent girls received from caregivers and peers included compliments, pressure to lose weight, teasing, and advice. Adolescent girls also reported being either influenced by or skeptical of the images presented in the media. Programs that promote caregiver-adolescent communication about body perceptions and that build on the adolescent girls' media skepticism may prove useful for their health-related attitudes and behaviors.
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Developing public health regulations for marijuana: lessons from alcohol and tobacco.
Am J Public Health
PUBLISHED: 04-17-2014
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Until November 2012, no modern jurisdiction had removed the prohibition on the commercial production, distribution, and sale of marijuana for nonmedical purposes-not even the Netherlands. Government agencies in Colorado and Washington are now charged with granting production and processing licenses and developing regulations for legal marijuana, and other states and countries may follow. Our goal is not to address whether marijuana legalization is a good or bad idea but, rather, to help policymakers understand the decisions they face and some lessons learned from research on public health approaches to regulating alcohol and tobacco over the past century.
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Development of a realistic in vivo bone metastasis model of human renal cell carcinoma.
Clin. Exp. Metastasis
PUBLISHED: 03-19-2014
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About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (?CT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.
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Vemurafenib-induced interface dermatitis manifesting as radiation-recall and a keratosis pilaris-like eruption.
J. Cutan. Pathol.
PUBLISHED: 03-11-2014
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Vemurafenib is a specific inhibitor of the V600E mutated BRAF protein kinase used for the treatment of unresectable or metastatic melanoma harboring this mutation. Multiple predictable side effects have been described with use of this targeted therapy, and implicate BRAF and mitogen activated protein kinase (MAPK) signaling pathways in their pathogenesis. Herein, we report the novel finding of an interface dermatitis in radiation recall and a keratosis pilaris-like clinical reaction in a patient treated with vemurafenib.
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Estimating health state utility values from discrete choice experiments--a QALY space model approach.
Health Econ
PUBLISHED: 03-09-2014
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Using discrete choice experiments (DCEs) to estimate health state utility values has become an important alternative to the conventional methods of Time Trade-Off and Standard Gamble. Studies using DCEs have typically used the conditional logit to estimate the underlying utility function. The conditional logit is known for several limitations. In this paper, we propose two types of models based on the mixed logit: one using preference space and the other using quality-adjusted life year (QALY) space, a concept adapted from the willingness-to-pay literature. These methods are applied to a dataset collected using the EQ-5D. The results showcase the advantages of using QALY space and demonstrate that the preferred QALY space model provides lower estimates of the utility values than the conditional logit, with the divergence increasing with worsening health states.
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Spheroid culture of LuCaP 147 as an authentic preclinical model of prostate cancer subtype with SPOP mutation and hypermutator phenotype.
Cancer Lett.
PUBLISHED: 03-07-2014
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LuCaP serially transplantable xenografts are valuable preclinical models of locally advanced or metastatic prostate cancer. For the first time, we recently succeeded in establishing and serially passaging spheroid cultures of several LuCaP xenografts. Here, we characterized in depth the molecular and cellular phenotype of LuCaP 147 cultures and found faithful retention of the characteristics of the original xenograft, including immunophenotype, genetic fidelity, gene expression profile and responsiveness to androgen. Furthermore, we demonstrated capabilities for high-throughput drug screening and that anti-cancer agents induced cell cycle arrest and apoptosis in spheroid cultures. Finally, we showed that cells formed tumors when re-introduced into mice, providing an authentic in vitro-in vivo preclinical model of a subtype of prostate cancer with a hypermutator phenotype and an SPOP mutation.
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Longitudinal evaluation of quality of life in 288 patients with neurofibromatosis 2.
J. Neurol.
PUBLISHED: 02-25-2014
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Advances in molecular biology have resulted in novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need for robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an outcome measure for treatment in a multi-centre study. NFTI-QOL was related to clinician-rated severity (ClinSev) and genetic severity (GenSev) over repeated visits. Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach's alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed a good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype.
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A systematic review of outcome data for dermatofibrosarcoma protuberans with and without fibrosarcomatous change.
J. Am. Acad. Dermatol.
PUBLISHED: 02-21-2014
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To our knowledge, no systematic review of dermatofibrosarcoma protuberans (DFSP) outcomes based on the presence or absence of fibrosarcomatous (FS) change has been performed.
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Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.
Nature
PUBLISHED: 02-18-2014
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The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor ROR?t. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.
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Changing pigmentation in a solitary scalp lesion.
Dermatol. Online J.
PUBLISHED: 02-14-2014
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A healthy 66 year-old man presented with a complaint of changes within a nodule on the scalp, which had first appeared over 10 years prior. He had no previous history of skin cancer. On physical examination a solitary, asymmetric, purple-black nodule with irregular borders was identified on the right vertex of his scalp. The remainder of his examination did not reveal any additional lesions.
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Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial.
BMJ
PUBLISHED: 02-12-2014
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To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women.
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Elective birth at 37 weeks' gestation for women with an uncomplicated twin pregnancy.
Cochrane Database Syst Rev
PUBLISHED: 02-11-2014
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The optimal timing of birth for women with an otherwise uncomplicated twin pregnancy at term is uncertain, with clinical support for both elective delivery at 37 weeks, as well as expectant management (awaiting the spontaneous onset of labour).
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Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.
Mol Genet Genomic Med
PUBLISHED: 02-06-2014
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Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.
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Recurrent dermatitis and dermal hypersensitivity following a jellyfish sting: a case report and review of literature.
Pediatr Dermatol
PUBLISHED: 02-04-2014
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Jellyfish envenomation often causes an immediate painful vesiculopapular eruption. Less commonly it can cause a type IV allergic hypersensitivity that manifests with delayed or recurrent cutaneous lesions at the primary site or distant from the primary site. These secondary reactivations may be related to high antijellyfish immunoglobulin levels, intracutaneously sequestered antigen, or cross-reacting venom. Immunomodulators such as pimecrolimus and tacrolimus and topical and intralesional corticosteroid therapy decrease this recurrent dermatitis. We report a case of a 9-year-old girl with a recurrent jellyfish dermatitis lasting more than 1 year after the initial envenomation. The dermatitis finally resolved after treatment with tacrolimus and intralesional triamcinolone acetonide therapy.
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Characterization factors for terrestrial acidification at the global scale: A systematic analysis of spatial variability and uncertainty.
Sci. Total Environ.
PUBLISHED: 01-29-2014
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Characterization factors (CFs) are used in life cycle assessment (LCA) to quantify the potential impact per unit of emission. CFs are obtained from a characterization model which assess the environmental mechanisms along the cause-effect chain linking an emission to its potential damage on a given area of protection, such as loss in ecosystem quality. Up to now, CFs for acidifying emissions did not cover the global scale and were only representative of their characterization model geographical scope. Consequently, current LCA practices implicitly assume that all emissions from a global supply chain occur within the continent referring to the characterization method geographical scope. This paper provides worldwide 2°×2.5° spatially-explicit CFs, representing the change in relative loss of terrestrial vascular plant species due to an emission change of nitrogen oxides (NOx), ammonia (NH3) and sulfur dioxide (SO2). We found that spatial variability in the CFs is much larger compared to statistical uncertainty (six orders of magnitude vs. two orders of magnitude). Spatial variability is mainly caused by the atmospheric fate factor and soil sensitivity factor, while the ecological effect factor is the dominant contributor to the statistical uncertainty. The CFs provided in our study allow the worldwide spatially explicit evaluation of life cycle impacts related to acidifying emissions. This opens the door to evaluate regional life cycle emissions of different products in a global economy.
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Expertise facilitates the transfer of anticipation skill across domains.
Q J Exp Psychol (Hove)
PUBLISHED: 01-25-2014
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It is unclear whether perceptual-motor skill transfer is based upon similarity between the learning and transfer domains per identical elements theory, or facilitated by an understanding of underlying principles in accordance with general principle theory. Here, the predictions of identical elements theory, general principle theory, and aspects of a recently proposed model for the transfer of perceptual-motor skill with respect to expertise in the learning and transfer domains are examined. The capabilities of expert karate athletes, near-expert karate athletes, and novices to anticipate and respond to stimulus skills derived from taekwondo and Australian football were investigated in ecologically valid contexts using an in situ temporal occlusion paradigm and complex whole-body perceptual-motor skills. Results indicated that the karate experts and near-experts are as capable of using visual information to anticipate and guide motor skill responses as domain experts and near-experts in the taekwondo transfer domain, but only karate experts could perform like domain experts in the Australian football transfer domain. Findings suggest that transfer of anticipation skill is based upon expertise and an understanding of principles but may be supplemented by similarities that exist between the stimulus and response elements of the learning and transfer domains.
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Supply of buprenorphine waivered physicians: The influence of state policies.
J Subst Abuse Treat
PUBLISHED: 01-24-2014
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Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine.
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Including exposure variability in the life cycle impact assessment of indoor chemical emissions: the case of metal degreasing.
Environ Int
PUBLISHED: 01-24-2014
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The present paper describes a method that accounts for variation in indoor chemical exposure settings and accompanying human toxicity in life cycle assessment (LCA). Metal degreasing with dichloromethane was used as a case study to show method in practice. We compared the human toxicity related to the degreasing of 1m(2) of metal surface in different exposure scenarios for industrial workers, professional users outside industrial settings, and home consumers. The fraction of the chemical emission that is taken in by exposed individuals (i.e. the intake fraction) was estimated on the basis of operational conditions (e.g. exposure duration), and protective measures (e.g. local exhaust ventilation). The introduction of a time-dependency and a correction for protective measures resulted in reductions in the intake fraction of up to 1.5 orders of magnitude, compared to application of existing, less advanced models. In every exposure scenario, the life cycle impacts for human toxicity were mainly caused by indoor exposure to metal degreaser (>60%). Emissions released outdoors contributed up to 22% of the life cycle impacts for human toxicity, and the production of metal degreaser contributed up to 19%. These findings illustrate that human toxicity from indoor chemical exposure should not be disregarded in LCA case studies. Particularly when protective measures are taken or in the case of a short duration (1h or less), we recommend the use of our exposure scenario-specific approach.
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Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium.
Alireza Moayyeri, Yi-Hsiang Hsu, David Karasik, Karol Estrada, Su-Mei Xiao, Carrie Nielson, Priya Srikanth, Sylvie Giroux, Scott G Wilson, Hou-Feng Zheng, Albert V Smith, Stephen R Pye, Paul J Leo, Alexander Teumer, Joo-Yeon Hwang, Claes Ohlsson, Fiona McGuigan, Ryan L Minster, Caroline Hayward, José M Olmos, Leo-Pekka Lyytikäinen, Joshua R Lewis, Karin M A Swart, Laura Masi, Chris Oldmeadow, Elizabeth G Holliday, Sulin Cheng, Natasja M van Schoor, Nicholas C Harvey, Marcin Kruk, Fabiola Del Greco M, Wilmar Igl, Olivia Trummer, Efi Grigoriou, Robert Luben, Ching-Ti Liu, Yanhua Zhou, Ling Oei, Carolina Medina-Gomez, Joseph Zmuda, Greg Tranah, Suzanne J Brown, Frances M Williams, Nicole Soranzo, Johanna Jakobsdottir, Kristin Siggeirsdottir, Kate L Holliday, Anke Hannemann, Min Jin Go, Melissa Garcia, Ozren Polašek, Marika Laaksonen, Kun Zhu, Anke W Enneman, Mark McEvoy, Roseanne Peel, Pak Chung Sham, Maciej Jaworski, Asa Johansson, Andrew A Hicks, Pawel Pludowski, Rodney Scott, Rosalie A M Dhonukshe-Rutten, Nathalie van der Velde, Mika Kähönen, Jorma S Viikari, Harri Sievänen, Olli T Raitakari, Jesús González-Macías, José L Hernández, Dan Mellström, Osten Ljunggren, Yoon Shin Cho, Uwe Völker, Matthias Nauck, Georg Homuth, Henry Völzke, Robin Haring, Matthew A Brown, Eugene McCloskey, Geoffrey C Nicholson, Richard Eastell, John A Eisman, Graeme Jones, Ian R Reid, Elaine M Dennison, John Wark, Steven Boonen, Dirk Vanderschueren, Frederick C W Wu, Thor Aspelund, J Brent Richards, Doug Bauer, Albert Hofman, Kay-Tee Khaw, George Dedoussis, Barbara Obermayer-Pietsch, Ulf Gyllensten, Peter P Pramstaller, Roman S Lorenc, Cyrus Cooper, Annie Wai Chee Kung, Paul Lips, Markku Alen, John Attia, Maria Luisa Brandi, Lisette C P G M de Groot, Terho Lehtimäki, José A Riancho, Harry Campbell, Yongmei Liu, Tamara B Harris, Kristina Akesson, Magnus Karlsson, Jong-Young Lee, Henri Wallaschofski, Emma L Duncan, Terence W O'Neill, Vilmundur Gudnason, Timothy D Spector, François Rousseau, Eric Orwoll, Steven R Cummings, Nick J Wareham, Fernando Rivadeneira, André G Uitterlinden, Richard L Prince, Douglas P Kiel, Jonathan Reeve, Stephen K Kaptoge.
Hum. Mol. Genet.
PUBLISHED: 01-14-2014
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Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 × 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 × 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 × 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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The PACT study protocol: a time series study investigating the impact, acceptability and cost of an integrated model for psychosocial screening, care and treatment of patients with urological and head and neck cancers.
BMJ Open
PUBLISHED: 01-14-2014
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While there is good evidence of the effectiveness of a variety of interventions and services to prevent and/or relieve distress experienced by people affected by cancer, much of this psychosocial morbidity is undetected and untreated, with consequent exacerbated suffering, decreased satisfaction with care, impaired adherence to treatment regimens and poorer morbidity and mortality outcomes. The objective of this study is to develop, implement and assess the impact, acceptability and cost of an integrated, patient-centred Psychosocial Assessment, Care and Treatment (PACT) model of care for patients with urological and head and neck cancers.
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Follicular induction overlying a dermatofibrosarcoma protuberans.
Am J Dermatopathol
PUBLISHED: 01-08-2014
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The term "induction" has been used to describe epidermal changes overlying a dermatofibroma (DF). Follicular induction is most often associated with DF, but can be observed in other lesions, including focal mucinosis, nevus sebaceous, seborrheic keratosis, wart, neurofibroma, and scars. Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic tumor that may be difficult to distinguish from DF. In contrast to DF, the epidermis overlying DFSP is usually attenuated or ulcerated. Here, we report a case of DFSP exhibiting follicular induction of the overlying epidermis. This epidermal change has been rarely reported in DFSP and may present a diagnostic pitfall in superficially sampled lesions.
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The effects of medical marijuana laws on potency.
Int. J. Drug Policy
PUBLISHED: 01-06-2014
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Marijuana potency has risen dramatically over the past two decades. In the United States, it is unclear whether state medical marijuana policies have contributed to this increase.
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The association between drugs frequently used by the elderly and vitamin D blood levels: a review of observational and experimental studies.
Drugs Aging
PUBLISHED: 01-04-2014
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The risk of adverse drug reactions (ADRs) rises with increasing age. In the field of ADRs, drug-nutrient interactions (DNIs) are a relatively unexplored area. More knowledge will contribute to the simple prevention of this type of ADR. As the prevalence of vitamin D deficiency in the elderly is high, the primary objective of this review is to evaluate the literature on the relationship between drug use and vitamin D status, focusing on medicines commonly used by the elderly. PubMed was searched for human epidemiological and clinical studies published until early 2013, investigating the relationship between vitamin D blood levels and use of drugs from one of the following groups: proton pump inhibitors (PPIs), biguanides, vitamin K antagonists, platelet aggregation inhibitors, thiazide diuretics, loop diuretics, beta-blocking agents, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II antagonists, statins, benzodiazepines, and antidepressants. A total of 63 publications were identified. Thiazide diuretics, statins, and calcium channel blocking agents were the most frequently studied drug groups. Associations between thiazides and vitamin D were mixed (n = 22), statins had no or positive associations (n = 16) and calcium blockers were not associated or were negatively associated with vitamin D (n = 10). In conclusion, several knowledge gaps exist on the relationship between drug use and vitamin D blood levels. Available data are scarce (particularly for the aged), study characteristics are highly variable, and found associations may be confounded by, amongst other things, the underlying disease. Nonetheless, this review provides a basis for future research on ADRs that contribute to nutrient deficiencies.
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Deriving a preference-based utility measure for cancer patients from the European Organisation for the Research and Treatment of Cancer's Quality of Life Questionnaire C30: a confirmatory versus exploratory approach.
Patient Relat Outcome Meas
PUBLISHED: 01-01-2014
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Multi attribute utility instruments (MAUIs) are preference-based measures that comprise a health state classification system (HSCS) and a scoring algorithm that assigns a utility value to each health state in the HSCS. When developing a MAUI from a health-related quality of life (HRQOL) questionnaire, first a HSCS must be derived. This typically involves selecting a subset of domains and items because HRQOL questionnaires typically have too many items to be amendable to the valuation task required to develop the scoring algorithm for a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis is recommended for deriving a MAUI from a HRQOL measure.
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Hearing and facial function outcomes for neurofibromatosis 2 clinical trials.
Neurology
PUBLISHED: 11-20-2013
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Vestibular schwannomas are the hallmark of neurofibromatosis 2 (NF2), occurring in >95% of patients. These tumors develop on the vestibulocochlear nerve and are associated with significant morbidity due to hearing loss, tinnitus, imbalance, facial weakness, and risk of early mortality from brainstem compression. Although hearing loss and facial weakness have been identified as important functional outcomes for patients with NF2, there is a lack of consensus regarding appropriate endpoints in clinical trials.
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Functional outcome measures for NF1-associated optic pathway glioma clinical trials.
Neurology
PUBLISHED: 11-20-2013
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The goal of the Response Evaluation in Neurofibromatosis and Schwannomatosis Visual Outcomes Committee is to define the best functional outcome measures for future neurofibromatosis type 1 (NF1)-associated optic pathway glioma (OPG) clinical trials.
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Assessing the Importance of Spatial Variability versus Model Choices in Life Cycle Impact Assessment: The Case of Freshwater Eutrophication in Europe.
Environ. Sci. Technol.
PUBLISHED: 11-20-2013
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In Life Cycle Impact Assessment (LCIA) both spatial variability and model choices may be influential. In the case of the effect model, the effect factors differ with respect to their assumption of linear/nonlinear responses to increases in environmental stressor levels, and whether or not they account for the current stressor levels in the environment. Here, we derived spatially explicit characterization factors of phosphorus emissions causing eutrophication based on three different effect models (depicted by marginal, linear, and average effect factors) and two freshwater types (lakes and streams) and we performed an analysis of variance (ANOVA) to investigate how the selection of the effect models and the freshwater types influence the impacts of phosphorus emissions to freshwater on heterotrophic species. We found that 56% of the variability of ecological impacts per unit of phosphorus emission was explained, primarily, by the difference between freshwater types and, to a lesser extent, by the difference between effect models. The remaining variability was attributed to the spatial variation between river basins, mainly due to the variability in fate factors. Our study demonstrates the particular importance of accounting for spatial variability and model choices in LCIA.
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English consensus protocol evaluating candidacy for auditory brainstem and cochlear implantation in neurofibromatosis type 2.
Otol. Neurotol.
PUBLISHED: 10-19-2013
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Hearing loss resulting from bilateral vestibular schwannomas (VSs) has a significant effect on the quality of life of patients with neurofibromatosis Type 2 (NF2). A national consensus protocol was produced in England as a guide for cochlear implantation (CI) and auditory brainstem implantation (ABI) in these patients.
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Are the true impacts of adverse events considered in economic models of antineoplastic drugs? A systematic review.
Appl Health Econ Health Policy
PUBLISHED: 10-17-2013
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Antineoplastic drugs for cancer are often associated with adverse events, which influence patients physical health, quality of life and survival. However, the modelling of adverse events in cost-effectiveness analyses of antineoplastic drugs has not been examined.
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Equestrian perniosis: a report of 2 cases and a review of the literature.
Am J Dermatopathol
PUBLISHED: 09-14-2013
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Equestrian perniosis (EP) is a rare condition in which patients develop tender burning nodular plaques on their bilateral thighs after riding in the cold. These lesions tend to resolve rapidly with minimal exposure to cold, and wearing loose, layered warm clothing. Unlike acral perniosis, EP has no known systemic disease associations, although 2 reported cases did have elevated cold agglutinins. The histology of this disease is similar to perniosis; however, EP is distinct in that the perivascular lymphocytic infiltrate prominently involves the fat. In this case report, we discuss the clinical and histological findings in 2 cases of EP, including the first documented in a man.
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Valuing SF-6D Health States Using a Discrete Choice Experiment.
Med Decis Making
PUBLISHED: 09-11-2013
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We designed an online DCE and administered it to an Australia-representative online panel (n = 1017). A range of specifications investigating nonlinear preferences with respect to additional life expectancy were estimated using a random-effects probit model. The preferred model was then used to estimate a preference index such that full health and death were valued at 1 and 0, respectively, to provide an algorithm for Australian cost-utility analyses.
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A Tissue Graft Model of DNA Damage Response in the Normal and Malignant Human Prostate.
J. Urol.
PUBLISHED: 09-03-2013
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DNA damage responses are relevant to prostate cancer initiation, progression and treatment. Few models of the normal and malignant human prostate that maintain stromal-epithelial interactions in vivo exist in which to study DNA damage responses. We evaluated the feasibility of maintaining tissue slice grafts at subcutaneous vs subrenal capsular sites in RAG2(-/-)?C(-/-) mice to study the DNA damage responses of normal and malignant glands.
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EURRECA-Principles and future for deriving micronutrient recommendations.
Crit Rev Food Sci Nutr
PUBLISHED: 08-20-2013
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The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence (NoE) explored an approach for setting micronutrient recommendations, which would address the variation in recommendations across Europe. Therefore, a framework for deriving and using micronutrient Dietary Reference Values (DRVs) has been developed. This framework comprises four stages (defining the problem-monitoring and evaluating-deriving dietary reference values-using dietary reference values in policy making). The aim of the present paper is to use this framework to identify specific research gaps and needs related to (1) knowledge available on specific micronutrients (folate, iodine, iron, selenium, vitamin B12, vitamin D, and zinc) and (2) the methodology presented in the framework. Furthermore, the paper describes the different outputs that support the process like protocols, guidelines, systematic review databases, and peer-reviewed publications, as well as the principal routes of dissemination of these outputs to ensure their optimal uptake in policy, practice, and research collaborations. The importance of ensuring transparency in risk assessment and risk management, systematic searching the literature, and taking into account policy options is highlighted. [Supplementary materials are available for this article. Go to the publishers online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional tables.].
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EURRECA-Evidence-based methodology for deriving micronutrient recommendations.
Crit Rev Food Sci Nutr
PUBLISHED: 08-20-2013
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The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence explored the process of setting micronutrient recommendations to address the variance in recommendations across Europe. Work centered upon the transparent assessment of nutritional requirements via a series of systematic literature reviews and meta-analyses. In addition, the necessity of assessing nutritional requirements and the policy context of setting micronutrient recommendations was investigated. Findings have been presented in a framework that covers nine activities clustered into four stages: stage one "Defining the problem" describes Activities 1 and 2: "Identifying the nutrition-related health problem" and "Defining the process"; stage two "Monitoring and evaluating" describes Activities 3 and 7: "Establishing appropriate methods," and "Nutrient intake and status of population groups"; stage three "Deriving dietary reference values" describes Activities 4, 5, and 6: "Collating sources of evidence," "Appraisal of the evidence," and "Integrating the evidence"; stage four "Using dietary reference values in policy making" describes Activities 8 and 9: "Identifying policy options," and "Evaluating policy implementation." These activities provide guidance on how to resolve various issues when deriving micronutrient requirements and address the methodological and policy decisions, which may explain the current variation in recommendations across Europe. [Supplementary materials are available for this article. Go to the publishers online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.].
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Relationship of cigarette-related perceptions to cigarette design features: findings from the 2009 ITC U.S. Survey.
Nicotine Tob. Res.
PUBLISHED: 08-13-2013
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Many governments around the world have banned the use of misleading cigarette descriptors such as "light" and "mild" because the cigarettes so labeled were found not to reduce smokers health risks. However, underlying cigarette design features, which are retained in many brands, likely contribute to ongoing belief that these cigarettes are less harmful by producing perceptions of lightness/smoothness through lighter taste and reduced harshness and irritation.
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Neurofibromatosis type 1 (NF1): diagnosis and management.
Handb Clin Neurol
PUBLISHED: 08-13-2013
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Neurofibromatosis 1 (NF1) is an inherited neurocutaneous disease that has a major impact on the nervous system, eye, skin, and bone. Individuals with NF1 have a predisposition to benign and malignant tumor formation and the hallmark lesion is the neurofibroma, a benign peripheral nerve sheath tumor. The gene for NF1 was cloned on chromosome 17q11.2 and neurofibromin, the NF1 protein, controls cell growth and proliferation by regulating the proto-oncogene Ras and cyclic adenosine monophosphate (AMP). Advances in molecular biology and mouse models of disease have enhanced our understanding of the pathogenesis of NF1 complications and facilitated targeted therapy. Progress has been made in developing robust clinical and radiological outcome measures and clinical trials are underway for children with learning difficulties and for individuals with symptomatic plexiform neurofibromas.
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Quantifying the trade-off between parameter and model structure uncertainty in life cycle impact assessment.
Environ. Sci. Technol.
PUBLISHED: 08-01-2013
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To enhance the use of quantitative uncertainty assessments in life cycle impact assessment practice, we suggest to quantify the trade-off between parameter uncertainty, i.e. any uncertainty associated with data and methods used to quantify the model parameters, and model structure uncertainty, i.e. the uncertainty about the relations and mechanisms being studied. In this paper we show the trade-off between the two types of uncertainty in a case of maize production with a focus on freshwater ecotoxicity due to pesticide application in The Netherlands. Parameter uncertainty in pesticide emissions, chemical-specific data, effect and damage data, and fractions of metabolite formation of degradation products was statistically quantified via probabilistic simulation, i.e. Monte Carlo simulation. Model structure uncertainties regarding the concentration-response model to be included, the selection of the damage model, and the inclusion of pesticide transformation products were assessed via discrete choice analysis. We conclude that to arrive at a minimum level of overall uncertainty the linear concentration-response model is preferable, while the transformation products may be excluded. Selecting the damage model has a relatively low influence on the overall uncertainty. Our study shows that quantifying the trade-off between different types of uncertainty can help to identify optimal model complexity from an uncertainty point of view.
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Bridging the gap between life cycle inventory and impact assessment for toxicological assessments of pesticides used in crop production.
Chemosphere
PUBLISHED: 07-30-2013
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In Life Cycle Assessment (LCA), the Life Cycle Inventory (LCI) provides emission data to the various environmental compartments and Life Cycle Impact Assessment (LCIA) determines the final distribution, fate and effects. Due to the overlap between the Technosphere (anthropogenic system) and Ecosphere (environment) in agricultural case studies, it is, however, complicated to establish what LCI needs to capture and where LCIA takes over. This paper aims to provide guidance and improvements of LCI/LCIA boundary definitions, in the dimensions of space and time. For this, a literature review was conducted to provide a clear overview of available methods and models for both LCI and LCIA regarding toxicological assessments of pesticides used in crop production. Guidelines are provided to overcome the gaps between LCI and LCIA modeling, and prevent the overlaps in their respective operational spheres. The proposed framework provides a starting point for LCA practitioners to gather the right data and use the proper models to include all relevant emission and exposure routes where possible. It is also able to predict a clear distinction between efficient and inefficient management practices (e.g. using different application rates, washing and rinsing management, etc.). By applying this framework for toxicological assessments of pesticides, LCI and LCIA can be directly linked, removing any overlaps or gaps in between the two distinct LCA steps.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.