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Find video protocols related to scientific articles indexed in Pubmed.
Combat-Acquired Traumatic Brain Injury, Posttraumatic Stress Disorder, and Their Relative Associations With Postdeployment Binge Drinking.
J Head Trauma Rehabil
PUBLISHED: 10-14-2014
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To examine whether experiencing a traumatic brain injury (TBI) on a recent combat deployment was associated with postdeployment binge drinking, independent of posttraumatic stress disorder (PTSD).
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Predictors of Army National Guard and Reserve members' use of Veteran Health Administration health care after demobilizing from OEF/OIF deployment.
Mil Med
PUBLISHED: 10-01-2014
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This study described rates and predictors of Army National Guard and Army Reserve members' enrollment in and utilization of Veteran Health Administration (VHA) services in the 365 days following demobilization from an index deployment. We also explored regional and VHA facility variation in serving eligible members in their catchment areas. The sample included 125,434 Army National Guard and 48,423 Army Reserve members who demobilized after a deployment ending between FY 2008 and FY 2011. Demographic, geographic, deployment, and Military Health System eligibility were derived from Defense Enrollment Eligibility Reporting System and "Contingency Tracking System" data. The VHA National Patient Care Databases were used to ascertain VHA utilization and status (e.g., enrollee, TRICARE). Logistic regression models were used to evaluate predictors of VHA utilization as an enrollee in the year following demobilization. Of the study members demobilizing during the observation period, 56.9% of Army National Guard members and 45.7% of Army Reserve members utilized VHA as an enrollee within 12 months. Demographic, regional, health coverage, and deployment-related factors were associated with VHA enrollment and utilization, and significant variation by VHA facility was found. These findings can be useful in the design of specific outreach efforts to improve linkage from the Military Health System to the VHA.
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Sickle cell disease: a neglected chronic disease of increasing global health importance.
Arch. Dis. Child.
PUBLISHED: 09-21-2014
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Sickle cell disease (SCD) is a single gene disorder causing a debilitating systemic syndrome characterised by chronic anaemia, acute painful episodes, organ infarction and chronic organ damage and by a significant reduction in life expectancy. The origin of SCD lies in the malarial regions of the tropics where carriers are protected against death from malaria and hence enjoy an evolutionary advantage. More recently, population migration has meant that SCD now has a worldwide distribution and that a substantial number of children are born with the condition in higher-income areas, including large parts of Europe and North and South America. Newborn screening, systematic clinical follow-up and prevention of sepsis and organ damage have led to an increased life expectancy among people with SCD in many such countries; however, in resource-limited settings where the majority continue to be born, most affected children continue to die in early childhood, usually undiagnosed, due to the lack of effective programmes for its early detection and treatment. As new therapies emerge, potentially leading to disease amelioration or cure, it is of paramount importance that the significant burden of SCD in resource-poor countries is properly recognised.
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Stabilization of Cellular RNA in Blood During Storage at Room Temperature: A Comparison of Cell-Free RNA BCT(®) with K3EDTA Tubes.
Mol Diagn Ther
PUBLISHED: 09-02-2014
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Messenger RNA (mRNA) expression levels in blood cells are important in disease diagnosis, prognosis and biomarker discovery research. Accurate measurements of intracellular mRNA levels in blood cells depend upon several pre-analytical factors, including delays in RNA extraction from blood after phlebotomy. Dramatic changes in mRNA expression levels caused by delays in blood sample processing may render such samples unsuitable for gene expression analysis.
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Knowing who to trust: exploring the role of 'ethical metadata' in mediating risk of harm in collaborative genomics research in Africa.
BMC Med Ethics
PUBLISHED: 08-13-2014
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The practice of making datasets publicly available for use by the wider scientific community has become firmly integrated in genomic science. One significant gap in literature around data sharing concerns how it impacts on scientists' ability to preserve values and ethical standards that form an essential component of scientific collaborations. We conducted a qualitative sociological study examining the potential for harm to ethnic groups, and implications of such ethical concerns for data sharing. We focused our empirical work on the MalariaGEN Consortium, one of the first international collaborative genomics research projects in Africa.
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Phyllosphere microbiota composition and microbial community transplantation on lettuce plants grown indoors.
MBio
PUBLISHED: 08-12-2014
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The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of microorganisms residing on plants in nature. We found that Romaine lettuce grown in the laboratory contained 10- to 100-fold lower numbers of bacteria than age-matched, field-grown lettuce. The bacterial diversity on laboratory-grown plants was also significantly lower and contained relatively higher proportions of Betaproteobacteria as opposed to the Gammaproteobacteria-enriched communities on field lettuce. Incubation of field-grown Romaine lettuce plants in environmental growth chambers for 2 weeks resulted in bacterial cell densities and taxa similar to those on plants in the field but with less diverse bacterial populations overall. In comparison, the inoculation of laboratory-grown Romaine lettuce plants with either freshly collected or cryopreserved microorganisms recovered from field lettuce resulted in the development of a field-like microbiota on the lettuce within 2 days of application. The survival of an inoculated strain of Escherichia coli O157:H7 was unchanged by microbial community transfer; however, the inoculation of E. coli O157:H7 onto those plants resulted in significant shifts in the abundance of certain taxa. This finding was strictly dependent on the presence of a field-associated as opposed to a laboratory-associated microbiota on the plants. Phyllosphere microbiota transplantation in the laboratory will be useful for elucidating microbial interactions on plants that are important to agriculture and microbial food safety.
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Role of SPECT/CT compared with MRI in the diagnosis and management of patients with wrist trauma occult fractures.
Clin Nucl Med
PUBLISHED: 08-07-2014
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The diagnosis of wrist fractures, especially scaphoid fractures, remains a challenge because of nonunion risk. Currently, new hybrid technologies are emerging such as SPECT/CT systems, which combine functional and anatomical data sets. So, we wanted to evaluate the utility of SPECT/CT in the management of occult carpal fractures.
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Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
Christopher J L Murray, Katrina F Ortblad, Caterina Guinovart, Stephen S Lim, Timothy M Wolock, D Allen Roberts, Emily A Dansereau, Nicholas Graetz, Ryan M Barber, Jonathan C Brown, Haidong Wang, Herbert C Duber, Mohsen Naghavi, Daniel Dicker, Lalit Dandona, Joshua A Salomon, Kyle R Heuton, Kyle Foreman, David E Phillips, Thomas D Fleming, Abraham D Flaxman, Bryan K Phillips, Elizabeth K Johnson, Megan S Coggeshall, Foad Abd-Allah, Semaw Ferede Abera, Jerry P Abraham, Ibrahim Abubakar, Laith J Abu-Raddad, Niveen Me Abu-Rmeileh, Tom Achoki, Austine Olufemi Adeyemo, Arsène Kouablan Adou, José C Adsuar, Emilie Elisabet Agardh, Dickens Akena, Mazin J Al Kahbouri, Deena Alasfoor, Mohammed I Albittar, Gabriel Alcalá-Cerra, Miguel Angel Alegretti, Zewdie Aderaw Alemu, Rafael Alfonso-Cristancho, Samia Alhabib, Raghib Ali, François Alla, Peter J Allen, Ubai Alsharif, Elena Alvarez, Nelson Alvis-Guzmán, Adansi A Amankwaa, Azmeraw T Amare, Hassan Amini, Walid Ammar, Benjamin O Anderson, Carl Abelardo T Antonio, Palwasha Anwari, Johan Arnlöv, Valentina S Arsic Arsenijevic, Ali Artaman, Rana J Asghar, Reza Assadi, Lydia S Atkins, Alaa Badawi, Kalpana Balakrishnan, Amitava Banerjee, Sanjay Basu, Justin Beardsley, Tolesa Bekele, Michelle L Bell, Eduardo Bernabé, Tariku Jibat Beyene, Neeraj Bhala, Ashish Bhalla, Zulfiqar A Bhutta, Aref Bin Abdulhak, Agnes Binagwaho, Jed D Blore, Berrak Bora Basara, Dipan Bose, Michael Brainin, Nicholas Breitborde, Carlos A Castañeda-Orjuela, Ferrán Catalá-López, Vineet K Chadha, Jung-Chen Chang, Peggy Pei-Chia Chiang, Ting-Wu Chuang, Mercedes Colomar, Leslie Trumbull Cooper, Cyrus Cooper, Karen J Courville, Benjamin C Cowie, Michael H Criqui, Rakhi Dandona, Anand Dayama, Diego De Leo, Louisa Degenhardt, Borja del Pozo-Cruz, Kebede Deribe, Don C Des Jarlais, Muluken Dessalegn, Samath D Dharmaratne, Ugur Dilmen, Eric L Ding, Tim R Driscoll, Adnan M Durrani, Richard G Ellenbogen, Sergey Petrovich Ermakov, Alireza Esteghamati, Emerito Jose A Faraon, Farshad Farzadfar, Seyed-Mohammad Fereshtehnejad, Daniel Obadare Fijabi, Mohammad H Forouzanfar, Urbano Fra Paleo, Lynne Gaffikin, Amiran Gamkrelidze, Fortuné Gbètoho Gankpé, Johanna M Geleijnse, Bradford D Gessner, Katherine B Gibney, Ibrahim Abdelmageem Mohamed Ginawi, Elizabeth L Glaser, Philimon Gona, Atsushi Goto, Hebe N Gouda, Harish Chander Gugnani, Rajeev Gupta, Rahul Gupta, Nima Hafezi-Nejad, Randah Ribhi Hamadeh, Mouhanad Hammami, Graeme J Hankey, Hilda L Harb, Josep Maria Haro, Rasmus Havmoeller, Simon I Hay, Mohammad T Hedayati, Ileana B Heredia Pi, Hans W Hoek, John C Hornberger, H Dean Hosgood, Peter J Hotez, Damian G Hoy, John J Huang, Kim M Iburg, Bulat T Idrisov, Kaire Innos, Kathryn H Jacobsen, Panniyammakal Jeemon, Paul N Jensen, Vivekanand Jha, Guohong Jiang, Jost B Jonas, Knud Juel, Haidong Kan, Ida Kankindi, Nadim E Karam, André Karch, Corine Kakizi Karema, Anil Kaul, Norito Kawakami, Dhruv S Kazi, Andrew H Kemp, André Pascal Kengne, Andre Keren, Maia Kereselidze, Yousef Saleh Khader, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmed Khan, Young-Ho Khang, Irma Khonelidze, Yohannes Kinfu, Jonas M Kinge, Luke Knibbs, Yoshihiro Kokubo, S Kosen, Barthélemy Kuate Defo, Veena S Kulkarni, Chanda Kulkarni, Kaushalendra Kumar, Ravi B Kumar, G Anil Kumar, Gene F Kwan, Taavi Lai, Arjun Lakshmana Balaji, Hilton Lam, Qing Lan, Van C Lansingh, Heidi J Larson, Anders Larsson, Jong-Tae Lee, James Leigh, Mall Leinsalu, Ricky Leung, Yichong Li, Yongmei Li, Graça Maria Ferreira De Lima, Hsien-Ho Lin, Steven E Lipshultz, Shiwei Liu, Yang Liu, Belinda K Lloyd, Paulo A Lotufo, Vasco Manuel Pedro Machado, Jennifer H MacLachlan, Carlos Magis-Rodríguez, Marek Majdan, Christopher Chabila Mapoma, Wagner Marcenes, Melvin Barrientos Marzan, Joseph R Masci, Mohammad Taufiq Mashal, Amanda J Mason-Jones, Bongani M Mayosi, Tasara T Mazorodze, Abigail Cecilia Mckay, Peter A Meaney, Man Mohan Mehndiratta, Fabiola Mejia-Rodriguez, Yohannes Adama Melaku, Ziad A Memish, Walter Mendoza, Ted R Miller, Edward J Mills, Karzan Abdulmuhsin Mohammad, Ali H Mokdad, Glen Liddell Mola, Lorenzo Monasta, Marcella Montico, Ami R Moore, Rintaro Mori, Wilkister Nyaora Moturi, Mitsuru Mukaigawara, Kinnari S Murthy, Aliya Naheed, Kovin S Naidoo, Luigi Naldi, Vinay Nangia, K M Venkat Narayan, Denis Nash, Chakib Nejjari, Robert G Nelson, Sudan Prasad Neupane, Charles R Newton, Marie Ng, Muhammad Imran Nisar, Sandra Nolte, Ole F Norheim, Vincent Nowaseb, Luke Nyakarahuka, In-Hwan Oh, Takayoshi Ohkubo, Bolajoko O Olusanya, Saad B Omer, John Nelson Opio, Orish Ebere Orisakwe, Jeyaraj D Pandian, Christina Papachristou, Angel J Paternina Caicedo, Scott B Patten, Vinod K Paul, Boris Igor Pavlin, Neil Pearce, David M Pereira, Aslam Pervaiz, Konrad Pesudovs, Max Petzold, Farshad Pourmalek, Dima Qato, Amado D Quezada, D Alex Quistberg, Anwar Rafay, Kazem Rahimi, Vafa Rahimi-Movaghar, Sajjad Ur Rahman, Murugesan Raju, Saleem M Rana, Homie Razavi, Robert Quentin Reilly, Giuseppe Remuzzi, Jan Hendrik Richardus, Luca Ronfani, Nobhojit Roy, Nsanzimana Sabin, Mohammad Yahya Saeedi, Mohammad Ali Sahraian, Genesis May J Samonte, Monika Sawhney, Ione J C Schneider, David C Schwebel, Soraya Seedat, Sadaf G Sepanlou, Edson E Servan-Mori, Sara Sheikhbahaei, Kenji Shibuya, Hwashin Hyun Shin, Ivy Shiue, Rupak Shivakoti, Inga Dora Sigfusdottir, Donald H Silberberg, Andrea P Silva, Edgar P Simard, Jasvinder A Singh, Vegard Skirbekk, Karen Sliwa, Samir Soneji, Sergey S Soshnikov, Chandrashekhar T Sreeramareddy, Vasiliki Kalliopi Stathopoulou, Konstantinos Stroumpoulis, Soumya Swaminathan, Bryan L Sykes, Karen M Tabb, Roberto Tchio Talongwa, Eric Yeboah Tenkorang, Abdullah Sulieman Terkawi, Alan J Thomson, Andrew L Thorne-Lyman, Jeffrey A Towbin, Jefferson Traebert, Bach X Tran, Zacharie Tsala Dimbuene, Miltiadis Tsilimbaris, Uche S Uchendu, Kingsley N Ukwaja, Selen Begüm Uzun, Andrew J Vallely, Tommi J Vasankari, N Venketasubramanian, Francesco S Violante, Vasiliy Victorovich Vlassov, Stein Emil Vollset, Stephen Waller, Mitchell T Wallin, Linhong Wang, Xiaorong Wang, Yanping Wang, Scott Weichenthal, Elisabete Weiderpass, Robert G Weintraub, Ronny Westerman, Richard A White, James D Wilkinson, Thomas Neil Williams, Solomon Meseret Woldeyohannes, John Q Wong, Gelin Xu, Yang C Yang, Yuichiro Yano, Gokalp Kadri Yentur, Paul Yip, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Younis, Chuanhua Yu, Kim Yun Jin, Maysaa El Sayed Zaki, Yong Zhao, Yingfeng Zheng, Maigeng Zhou, Jun Zhu, Xiao Nong Zou, Alan D Lopez, Theo Vos.
Lancet
PUBLISHED: 07-22-2014
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The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
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Mild chlorodifluoroacylation of indoles via self-activation of sodium chlorodifluoroacetate.
Org. Lett.
PUBLISHED: 07-15-2014
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A mild acylation of N-alkylindoles is reported using sodium chlorodifluoroacetate (SCDA) to synthesize useful chlorodifluoroketones. Friedel-Crafts reactivity of carboxylate salts is unusual and is not observed in similar electron-deficient acetate salts such as sodium trifluoroacetate. Mechanistic experiments indicate that the characteristic ability of SCDA to generate difluorocarbene is responsible for the reaction pathway via self-activation to form the active ester.
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Quantification of ¹³C enrichments and isotopomer abundances for metabolic flux analysis using 1D NMR spectroscopy.
Methods Mol. Biol.
PUBLISHED: 07-06-2014
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The analysis of stable isotope incorporation following feeding of (13)C-labeled precursors to plant tissues provides the constraints necessary for metabolic flux analysis. This protocol describes the use of one-dimensional (1)H and (13)C nuclear magnetic resonance spectroscopy for the quantification of (13)C enrichments and isotopomer abundances in mixtures of metabolites or hydrolyzed biomass components.
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Missed opportunity for alcohol problem prevention among army active duty service members postdeployment.
Am J Public Health
PUBLISHED: 06-12-2014
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We identified to what extent the Department of Defense postdeployment health surveillance program identifies at-risk drinking, alone or in conjunction with psychological comorbidities, and refers service members who screen positive for additional assessment or care.
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A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots.
Elife
PUBLISHED: 05-21-2014
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Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or 'hotspots' of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead. These two measures were inversely correlated, indicating that children in homesteads at higher transmission acquire immunity more rapidly. This inverse correlation increased gradually with increasing spatial scale of analysis, and hotspots of febrile malaria were identified at every scale. We found hotspots within hotspots, down to the level of an individual homestead. Febrile malaria hotspots were temporally unstable, but 4 km radius hotspots could be targeted for 1 month following 1 month periods of surveillance.DOI: http://dx.doi.org/10.7554/eLife.02130.001.
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Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling.
J. Neurooncol.
PUBLISHED: 05-07-2014
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Hedgehog (Hh) signaling regulates the growth of malignant gliomas by a ligand-dependent mechanism. The cellular source of Sonic Hh ligand and mode of signaling have not been clearly defined due to the lack of methods to definitively identify neoplastic cells in glioma specimens. Using an antibody specific for mutant isocitrate dehydrogenase protein expression to identify glioma cells, we demonstrate that Sonic Hh ligand and the pathway components Patched1 (PTCH1) and GLI1 are expressed in neoplastic cells. Further, Sonic Hh ligand and its transcriptional targets, PTCH1 and GLI1, are expressed in mutually distinct populations of neoplastic cells. These findings support a paracrine mode of intratumoral Hh signaling in malignant gliomas.
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Burden of disease in adults admitted to hospital in a rural region of coastal Kenya: an analysis of data from linked clinical and demographic surveillance systems.
Lancet Glob Health
PUBLISHED: 05-01-2014
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Estimates of the burden of disease in adults in sub-Saharan Africa largely rely on models of sparse data. We aimed to measure the burden of disease in adults living in a rural area of coastal Kenya with use of linked clinical and demographic surveillance data.
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Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000.
Lancet Glob Health
PUBLISHED: 04-22-2014
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Changes in the geographical distribution of genetic disorders are often thought to happen slowly, especially when compared with infectious diseases. Whereas mutations, genetic drift, and natural selection take place over many generations, epidemics can spread through large populations within a few days or weeks. Nevertheless, population movements can interfere with these processes, and few studies have been done of their eff ect on genetic disorders. We aimed to investigate the eff ect of global migration on the distribution of the sickle-cell gene-the most common and clinically significant haemoglobin structural variant.
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Genetic determinants of glucose-6-phosphate dehydrogenase activity in Kenya.
BMC Med. Genet.
PUBLISHED: 03-31-2014
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The relationship between glucose-6-phosphate dehydrogenase (G6PD) deficiency and clinical phenomena such as primaquine-sensitivity and protection from severe malaria remains poorly defined, with past association studies yielding inconsistent and conflicting results. One possibility is that examination of a single genetic variant might underestimate the presence of true effects in the presence of unrecognized functional allelic diversity.
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Red foxes (Vulpes vulpes) and wild dogs (dingoes (Canis lupus dingo) and dingo/domestic dog hybrids), as sylvatic hosts for Australian Taenia hydatigena and Taenia ovis.
Int J Parasitol Parasites Wildl
PUBLISHED: 03-30-2014
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Foxes (n = 499), shot during vertebrate pest control programs, were collected in various sites in the Australian Capital Territory (ACT), New South Wales (NSW) and Western Australia (WA). Wild dogs (dingoes (Canis lupus dingo) and their hybrids with domestic dogs) (n = 52) captured also as part of vertebrate pest control programs were collected from several sites in the ACT and NSW. The intestine from each fox and wild dog was collected, and all Taenia tapeworms identified morphologically were collected and identified to species based on the DNA sequence of the small subunit of the mitochondrial ribosomal RNA (rrnS) gene. Taenia species were recovered from 6.0% of the ACT/NSW foxes, 5.1% of WA foxes and 46.1% of ACT/NSW wild dogs. Taenia ovis was recovered from two foxes, 1/80 from Jugiong, NSW and 1/102 from Katanning, WA. We confirm from rrnS sequences the presence of T. ovis in cysts from hearts and diaphragms and T aenia hydatigena in cysts from livers of sheep in Australia. T. ovis was not recovered from any of the wild dogs examined but T. hydatigena were recovered from 4(8.3%) wild dogs and a single fox. With foxes identified as a definitive host for T. ovis in Australia, new control strategies to stop transmission of T. ovis to sheep need to be adopted.
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Phase II trial of standard versus increased transfusion volume in Ugandan children with acute severe anemia.
BMC Med
PUBLISHED: 03-17-2014
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Severe anemia (SA, hemoglobin <6 g/dl) is a leading cause of pediatric hospital admission in Africa, with significant in-hospital mortality. The underlying etiology is often infectious, but specific pathogens are rarely identified. Guidelines developed to encourage rational blood use recommend a standard volume of whole blood (20 ml/kg) for transfusion, but this is commonly associated with a frequent need for repeat transfusion and poor outcome. Evidence is lacking on what hemoglobin threshold criteria for intervention and volume are associated with the optimal survival outcomes.
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Nutritional status of young children with inherited blood disorders in western Kenya.
Am. J. Trop. Med. Hyg.
PUBLISHED: 03-17-2014
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To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6-35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 ?g/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 ?mol/L. Unadjusted analyses showed that compared with normal children, homozygous ?(+)-thalassemia individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, homozygous ?(+)-thalassemia remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, ?(+)-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth.
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Alcohol use and alcohol-related consequences: associations with emotion regulation difficulties.
Am J Drug Alcohol Abuse
PUBLISHED: 03-05-2014
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Understanding factors associated with alcohol-related consequences is an important area of research. Emotional functioning has been associated with alcohol-related consequences but there is less research examining a comprehensive underlying model of emotional regulation. The Difficulties in Emotion Regulation Scale (DERS) is a recent measure developed to assess six facets of emotion regulation difficulties that contribute to overall emotional functioning.
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Normative data for modified Box and Blocks test measuring upper-limb function via motion capture.
J Rehabil Res Dev
PUBLISHED: 03-04-2014
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Motion analysis is an important tool for examining upper-limb function. Based on previous work demonstrating a modified Box and Blocks (BB) test with motion capture to assess prosthetic performance, we collected data in 16 nondisabled participants to establish normative kinematics for this test. Four motions of the modified BB test were analyzed to establish kinematic data for upper-limb and trunk motion. The test was repeated for right and left arms in standing and seated positions. Data were compared using a nonparametric Friedman test. No differences were found between right- and left-hand performance other than for task completion time. Small but significant differences were found for standing and seated performance, with slightly greater ranges in standing for axial trunk rotation, medial-lateral sternum displacement, and anterior-posterior hand displacement. The kinematic trajectories, however, were very consistent. The consistency in our nondisabled data suggests that normative kinematic trajectories can be defined for this task. This motion capture procedure may add to the understanding of movement in upper-limb impairment and may be useful for measuring the effect of interventions to improve upper-limb function.
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Combinatorial effects of malaria season, iron deficiency, and inflammation determine plasma hepcidin concentration in African children.
Blood
PUBLISHED: 03-04-2014
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Hepcidin is the master regulatory hormone that governs iron homeostasis and has a role in innate immunity. Although hepcidin has been studied extensively in model systems, there is less information on hepcidin regulation in global health contexts where iron deficiency (ID), anemia, and high infectious burdens (including malaria) all coexist but fluctuate over time. We evaluated iron status, hepcidin levels, and determinants of hepcidin in 2 populations of rural children aged ?8 years, in the Gambia and Kenya (total n = 848), at the start and end of a malaria season. Regression analyses and structural equation modeling demonstrated, for both populations, similar combinatorial effects of upregulating stimuli (iron stores and to a lesser extent inflammation) and downregulating stimuli (erythropoietic drive) on hepcidin levels. However, malaria season was also a significant factor and was associated with an altered balance of these opposing factors. Consistent with these changes, hepcidin levels were reduced whereas the prevalence of ID was increased at the end of the malaria season. More prevalent ID and lower hepcidin likely reflect an enhanced requirement for iron and an ability to efficiently absorb it at the end of the malaria season. These results, therefore, have implications for ID and malaria control programs.
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Stabilization of circulating tumor cells in blood using a collection device with a preservative reagent.
Cancer Cell Int.
PUBLISHED: 02-28-2014
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The enumeration and characterization of circulating tumor cells (CTCs) in the blood of cancer patients is useful for cancer prognostic and treatment monitoring purposes. The number of CTCs present in patient blood is very low; thus, robust technologies have been developed to enumerate and characterize CTCs in patient blood samples. One of the challenges to the clinical utility of CTCs is their inherent fragility, which makes these cells very unstable during transportation and storage of blood samples. In this study we investigated Cell-Free DNA BCT™ (BCT), a blood collection device, which stabilizes blood cells in a blood sample at room temperature (RT) for its ability to stabilize CTCs at RT for an extended period of time.
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An assessment of the impact of host polymorphisms on Plasmodium falciparum var gene expression patterns among Kenyan children.
BMC Infect. Dis.
PUBLISHED: 02-17-2014
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Host genotype accounts for a component of the variability in susceptibility to childhood Plasmodium falciparum malaria. However, despite numerous examples of host polymorphisms associated with tolerance or resistance to infection, direct evidence for an impact of host genetic polymorphisms on the in vivo parasite population is difficult to obtain. Parasite molecules whose expression is most likely to be associated with such adaptation are those that are directly involved in the host-parasite interaction. A prime candidate is the family of parasite var gene-encoded molecules on P. falciparum-infected erythrocytes, PfEMP1, which binds various host molecules and facilitates parasite sequestration in host tissues to avoid clearance by the spleen.
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A mild and selective Pd-mediated methodology for the synthesis of highly fluorescent 2-arylated tryptophans and tryptophan-containing peptides: a catalytic role for Pd(0) nanoparticles?
Chem. Commun. (Camb.)
PUBLISHED: 02-10-2014
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A Pd-mediated direct C-H bond functionalisation of tryptophan has been developed, both as a single amino acid residue and within peptides. Important mechanistic insight into this process has been gained by characterising a Pd catalytically competent nanoparticle phase which evolves during the early stages of reaction.
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Foamy macrophage responses in the rat lung following exposure to inhaled pharmaceuticals: a simple, pragmatic approach for inhaled drug development.
J Appl Toxicol
PUBLISHED: 01-30-2014
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Successes in the field of respiratory medicines are largely limited to three main target classes: ?2 -adrenergic receptor agonists, muscarinic antagonists and corticosteroids. A significant factor in attrition during the development of respiratory medicines is the induction of foamy macrophage responses, particularly, in rats. The term foamy macrophage describes a vacuolated cytoplasmic appearance, seen by light microscopy, which is ultrastructurally characterized by the presence of lysosomal lamellar bodies, neutral lipid droplets or drug particles. We propose a simple classification, based light-heartedly on the theme 'the good, the bad and the ugly', which allows important distinctions to be made between phenotypes, aetiologies and adversity. Foamy macrophages induced in rat lungs by exposure to inhaled ?2 -agonists, antimuscarinics and corticosteroids are simple aggregates of uniform cells without other associated pathologies. In contrast, macrophage reactions induced by some other inhaled drug classes are more complex, associated with neutrophilic or lymphocytic infiltrations with/without damage to the adjacent alveolar walls. Foamy macrophage responses induced by inhaled drugs may be ascribed to either phagocytosis of poorly soluble drug particles, or to pharmacology. Both corticosteroids and ?2 -agonists increase surfactant synthesis whereas muscarinic antagonists may decrease surfactant breakdown, due to inhibition of phospholipase C, both of which lead to phagocytosis of excess surfactant. Simple foamy macrophage responses are considered non-adverse, whereas ones that are more complex are designated as adverse. The development of foamy macrophage responses has led to confusion in interpretation and we hope this review helps clarify what is in fact a relatively simple, predictable, easily interpretable, commonly induced change.
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Epistasis between the haptoglobin common variant and ?+thalassemia influences risk of severe malaria in Kenyan children.
Blood
PUBLISHED: 01-29-2014
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Haptoglobin (Hp) scavenges free hemoglobin following malaria-induced hemolysis. Few studies have investigated the relationship between the common Hp variants and the risk of severe malaria, and their results are inconclusive. We conducted a case-control study of 996 children with severe Plasmodium falciparum malaria and 1220 community controls and genotyped for Hp, hemoglobin (Hb) S heterozygotes, and ?(+)thalassemia. Hb S heterozygotes and ?(+)thalassemia homozygotes were protected from severe malaria (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.07-0.18 and OR, 0.69; 95% CI, 0.53-0.91, respectively). The risk of severe malaria also varied by Hp genotype: Hp2-1 was associated with the greatest protection against severe malaria and Hp2-2 with the greatest risk. Meta-analysis of the current and published studies suggests that Hp2-2 is associated with increased risk of severe malaria compared with Hp2-1. We found a significant interaction between Hp genotype and ?(+)thalassemia in predicting risk of severe malaria: Hp2-1 in combination with heterozygous or homozygous ?(+)thalassemia was associated with protection from severe malaria (OR, 0.73; 95% CI, 0.54-0.99 and OR, 0.48; 95% CI, 0.32-0.73, respectively), but ?(+)thalassemia in combination with Hp2-2 was not protective. This epistatic interaction together with varying frequencies of ?(+)thalassemia across Africa may explain the inconsistent relationship between Hp genotype and malaria reported in previous studies.
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Verbal autopsy as a tool for identifying children dying of sickle cell disease: a validation study conducted in Kilifi district, Kenya.
BMC Med
PUBLISHED: 01-17-2014
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Sickle cell disease (SCD) is common in many parts of sub-Saharan Africa (SSA), where it is associated with high early mortality. In the absence of newborn screening, most deaths among children with SCD go unrecognized and unrecorded. As a result, SCD does not receive the attention it deserves as a leading cause of death among children in SSA. In the current study, we explored the potential utility of verbal autopsy (VA) as a tool for attributing underlying cause of death (COD) in children to SCD.
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HLA-B*57 elite suppressor and chronic progressor HIV-1 isolates replicate vigorously and cause CD4+ T cell depletion in humanized BLT mice.
J. Virol.
PUBLISHED: 01-03-2014
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Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain undetectable viral loads without antiretroviral therapy. The mechanism of control remains unclear, but the HLA-B*57 allele is overrepresented in cohorts of these patients. However, many HLA-B*57 patients develop progressive disease, and some studies have suggested that infection with defective viruses may be the cause of the lack of high levels of virus replication and disease progression in ES. We therefore performed a comprehensive comparative in vivo and in vitro characterization of viruses isolated from well-defined ES. For this purpose, we first performed full-genome sequence analysis and in vitro fitness assays on replication-competent isolates from HLA-B*57 ES and HLA-B*57 chronic progressors (CPs). Under our experimental conditions, we found that isolates from ES and CPs can replicate in vitro. However, since inherently these assays involve the use of unnaturally in vitro-activated cells, we also investigated the replication competence and pathogenic potential of these HIV isolates in vivo using humanized BLT mice. The results from these analyses demonstrate that virus isolates from ES are fully replication competent in vivo and can induce peripheral and systemic CD4 T cell depletion. These results provide the first direct in vivo evidence that viral fitness does not likely determine clinical outcome in HLA-B*57 patients and that elite suppressors can control replication-competent, fully pathogenic viruses. A better understanding of the immunological bases of viral suppression in ES will serve to inform novel approaches to preventive and therapeutic HIV vaccine design.
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American Board of Thoracic Surgery examination: fewer graduates, more failures.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 01-02-2014
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The American Board of Thoracic Surgery (ABTS) has noted a yearly decrease in the number of examination certificates being awarded, with only 93 certificates awarded in 2011. In 2003, the Accreditation Council for Graduate Medical Education required all programs to implement the 80-hour residency workweek. We hypothesized that this requirement has resulted in trainees being less capable of becoming successfully certified.
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Causes of death among persons of all ages within the Kilifi Health and Demographic Surveillance System, Kenya, determined from verbal autopsies interpreted using the InterVA-4 model.
Glob Health Action
PUBLISHED: 01-01-2014
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The vast majority of deaths in the Kilifi study area are not recorded through official systems of vital registration. As a result, few data are available regarding causes of death in this population.
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HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.
Glob Health Action
PUBLISHED: 01-01-2014
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As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data.
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Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.
Glob Health Action
PUBLISHED: 01-01-2014
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Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies.
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Pregnancy-related mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.
Glob Health Action
PUBLISHED: 01-01-2014
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Women continue to die in unacceptably large numbers around the world as a result of pregnancy, particularly in sub-Saharan Africa and Asia. Part of the problem is a lack of accurate, population-based information characterising the issues and informing solutions. Population surveillance sites, such as those operated within the INDEPTH Network, have the potential to contribute to bridging the information gaps.
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Mortality from external causes in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System Sites.
Glob Health Action
PUBLISHED: 01-01-2014
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Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings.
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Adult non-communicable disease mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.
Glob Health Action
PUBLISHED: 01-01-2014
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Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.
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Cause-specific childhood mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.
Glob Health Action
PUBLISHED: 01-01-2014
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Childhood mortality, particularly in the first 5 years of life, is a major global concern and the target of Millennium Development Goal 4. Although the majority of childhood deaths occur in Africa and Asia, these are also the regions where such deaths are least likely to be registered. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.
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Cause-specific mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.
Glob Health Action
PUBLISHED: 01-01-2014
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Because most deaths in Africa and Asia are not well documented, estimates of mortality are often made using scanty data. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering all deaths over time and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.
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The recognition of and care seeking behaviour for childhood illness in developing countries: a systematic review.
PLoS ONE
PUBLISHED: 01-01-2014
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Pneumonia, diarrhoea, and malaria are among the leading causes of death in children. These deaths are largely preventable if appropriate care is sought early. This review aimed to determine the percentage of caregivers in low- and middle-income countries (LMICs) with a child less than 5 years who were able to recognise illness in their child and subsequently sought care from different types of healthcare providers.
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A central role for dityrosine crosslinking of Amyloid-beta in Alzheimers disease.
Acta Neuropathol Commun
PUBLISHED: 12-03-2013
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Alzheimers disease (AD) is characterized by the deposition of insoluble amyloid plaques in the neuropil composed of highly stable, self-assembled Amyloid-beta (Abeta) fibrils. Copper has been implicated to play a role in Alzheimers disease. Dimers of Abeta have been isolated from AD brain and have been shown to be neurotoxic.
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The evolution of Bab paralog expression and abdominal pigmentation among Sophophora fruit fly species.
Evol. Dev.
PUBLISHED: 11-23-2013
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The evolution of gene networks lies at the heart of understanding trait divergence. Intrinsic to development is the dimension of time: a network must be altered during the correct phase of development to generate the appropriate phenotype. One model of developmental network evolution is the origination of dimorphic (male-specific) abdomen pigmentation in the fruit fly subgenus Sophophora. In Drosophila (D.) melanogaster, dimorphic pigmentation is controlled by the dimorphic expression of the paralogous Bab1 and Bab2 transcription factors that repress pigmentation. These expression patterns are thought to have evolved from a monomorphic ancestral state. Here we show that the spatial domain and contrast in dimorphic Bab expression increases during the latter half of pupal development, and this late pupal expression is necessary and sufficient to suppress pigmentation. Late pupal Bab expression was monomorphic for species from basal clades exhibiting monomorphic pigmentation, though dimorphic expression was observed in D. pseudoobscura that represents an intermediate-branching monomorphic clade. Among species from the dimorphic Sophophora clades, Bab expression was dimorphic, but a poor correlation was found between the domains of expression and male pigmentation. Lastly, while Bab paralog co-expression was generally observed, an instance of paralog-specific expression was found, indicating more complex regulatory mechanisms and mutational effects have shaped the evolution of the bab locus. These results highlight the importance of the time and place of Bab expression for pigmentation development and evolution, and suggest that dimorphism evolved early in Sophophora, but diversity in male pigmentation was not further shaped by alterations in Bab expression.
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Strategies for optimizing military physical readiness and preventing musculoskeletal injuries in the 21st century.
US Army Med Dep J
PUBLISHED: 10-23-2013
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With downsizing of the military services and significant budget cuts, it will be more important than ever to optimize the health and performance of individual service members. Musculoskeletal injuries (MSIs) represent a major threat to the health and fitness of Soldiers and other service members that degrade our nations ability to project military power. This affects both financial (such as the economic burden from medical, healthcare, and disability costs) and human manpower resources (Soldiers medically unable to optimally perform their duties and to deploy). For example, in 2012, MSIs represented the leading cause of medical care visits across the military services resulting in almost 2,200,000 medical encounters. They also result in more disability discharges than any other health condition. Nonbattle injuries (NBIs) have caused more medical evacuations (34%) from recent theaters of operation than any other cause including combat injuries. Physical training and sports are the main cause of these NBIs. The majority (56%) of these injuries are the direct result of physical training. Higher levels of physical fitness protect against such injuries; however, more physical training to improve fitness also causes higher injury rates. Thus, military physical training programs must balance the need for fitness with the risks of injuries. The Army has launched several initiatives that may potentially improve military physical readiness and reduce injuries. These include the US Army Training and Doctrine Commands Baseline Soldier Physical Readiness Requirements and Gender Neutral Physical Performance Standards studies, as well as the reimplementation of the Master Fitness Trainer program and the Army Medical Commands Soldier Medical Readiness and Performance Triad Campaigns. It is imperative for military leaders to understand that military physical readiness can be enhanced at the same time that MSIs are prevented. A strategic paradigm shift in the militarys approach to physical readiness policies is needed to avoid further degradation of warfighting capability in an era of austerity. We believe this can be best accomplished through leveraging scientific, evidence-based best practices by Army senior leadership which supports, prioritizes, and implements innovative, synchronized, and integrated human performance optimization/injury prevention policy changes.
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A survey of the trans-regulatory landscape for Drosophila melanogaster abdominal pigmentation.
Dev. Biol.
PUBLISHED: 09-10-2013
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Trait development results from the collaboration of genes interconnected in hierarchical networks that control which genes are activated during the progression of development. While networks are understood to change over developmental time, the alterations that occur over evolutionary times are much less clear. A multitude of transcription factors and a far greater number of linkages between transcription factors and cis-regulatory elements (CREs) have been found to structure well-characterized networks, but the best understood networks control traits that are deeply conserved. Fruit fly abdominal pigmentation may represent an optimal setting to study network evolution, as this trait diversified over short evolutionary time spans. However, the current understanding of the underlying network includes a small set of transcription factor genes. Here, we greatly expand this network through an RNAi-screen of 558 transcription factors. We identified 28 genes, including previously implicated abd-A, Abd-B, bab1, bab2, dsx, exd, hth, and jing, as well as 20 novel factors with uncharacterized roles in pigmentation development. These include genes which promote pigmentation, suppress pigmentation, and some that have either male- or female-limited effects. We show that many of these transcription factors control the reciprocal expression of two key pigmentation enzymes, whereas a subset controls the expression of key factors in a female-specific circuit. We found the pupal Abd-A expression pattern was conserved between species with divergent pigmentation, indicating diversity resulted from changes to other loci. Collectively, these results reveal a greater complexity of the pigmentation network, presenting numerous opportunities to map transcription factor-CRE interactions that structure trait development and numerous candidate loci to investigate as potential targets of evolution.
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Spatial distribution of G6PD deficiency variants across malaria-endemic regions.
Malar. J.
PUBLISHED: 09-05-2013
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Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquines widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants.
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Recurrent modification of a conserved cis-regulatory element underlies fruit fly pigmentation diversity.
PLoS Genet.
PUBLISHED: 08-01-2013
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The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages.
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Human milk for preterm infants: why, what, when and how?
Arch. Dis. Child. Fetal Neonatal Ed.
PUBLISHED: 07-26-2013
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A mothers expressed breast milk (MEBM) is overall the best feed for her preterm baby during the neonatal period, and is associated with improved short-term and long-term outcomes. Neonatal services should commit the resources needed to optimise its use. The place of banked donor expressed breast milk (DEBM) is less clear, but it probably has a role in reducing the risk of necrotising enterocolitis and sepsis in preterm infants at particularly high risk. There is considerable variation in the composition of human milk and nutrient fortification is often needed to achieve intrauterine growth rates. Human milk can transmit potentially harmful micro-organisms, and pasteurisation, which denatures some of the bioactive factors, is the only known way of preventing this. This is carried out for DEBM but not MEBM in the UK. Future research on human milk should focus on (a) critical exposure periods, (b) understanding better its bioactive properties, (c) the role of DEBM and (d) nutritional quality assurance.
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Rationale and methods of the Substance Use and Psychological Injury Combat Study (SUPIC): a longitudinal study of Army service members returning from deployment in FY2008-2011.
Subst Use Misuse
PUBLISHED: 07-23-2013
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The Substance Use and Psychological Injury Combat Study (SUPIC) will examine whether early detection and intervention for post-deployment problems among Army Active Duty and National Guard/Reservists returning from Iraq or Afghanistan are associated with improved long-term substance use and psychological outcomes. This paper describes the rationale and significance of SUPIC, and presents demographic and deployment characteristics of the study sample (N = 643,205), and self-reported alcohol use and health problems from the subsample with matched post-deployment health assessments (N = 487,600). This longitudinal study aims to provide new insight into the long-term post-deployment outcomes of Army members by combining service member data from the Military Health System and Veterans Health Administration.
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Traumatic brain injury among U.S. active duty military personnel and negative drinking-related consequences.
Subst Use Misuse
PUBLISHED: 07-23-2013
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This study used the 2008 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel to determine whether traumatic brain injury (TBI) is associated with past year drinking-related consequences. The study sample included currently drinking personnel who had a combat deployment in the past year and were home for ?6 months (N = 3,350). Negative binomial regression models were used to assess the incidence rate ratios of consequences, by TBI-level. Experiencing a TBI with a loss of consciousness for more than 20 minutes was significantly associated with consequences independent of demographics, combat exposure, posttraumatic stress disorder, and binge drinking. The studys limitations are noted.
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Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions.
PLoS Med.
PUBLISHED: 07-01-2013
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The global burden of sickle cell anaemia (SCA) is set to rise as a consequence of improved survival in high-prevalence low- and middle-income countries and population migration to higher-income countries. The host of quantitative evidence documenting these changes has not been assembled at the global level. The purpose of this study is to estimate trends in the future number of newborns with SCA and the number of lives that could be saved in under-five children with SCA by the implementation of different levels of health interventions.
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Traumatic carotid artery dissection.
Mil Med
PUBLISHED: 06-15-2013
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Traumatic carotid artery dissections are uncommon and potentially devastating injuries that often have a delayed presentation. Soldiers often engage in leisure, training, and combat activities that place them at risk for sustaining an injury that causes a carotid artery dissection. To compound matters, spontaneous dissections are being more frequently recognized as well. Clinicians must be thorough in their history taking and maintain an elevated level of suspicion for this injury when presented with neurologic symptoms suggestive of head and neck pathology. This case study illustrates the difficulties encountered in arriving at a timely, correct diagnosis and offers treatment plan options. We hope that this case study will facilitate the early recognition and treatment of carotid artery dissections in the future.
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A novel blood collection device stabilizes cell-free RNA in blood during sample shipping and storage.
BMC Res Notes
PUBLISHED: 05-23-2013
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Cell-free RNA (cfRNA) naturally occurs in blood and has clinical significance. Accurate quantification of these extracellular RNAs in whole blood is hindered by the simultaneous unintended release of cellular RNA and degradation of cfRNA after blood draw. An appropriate blood collection device is needed to stabilize cfRNA during blood processing, transportation and storage, which will ensure cfRNA test reliability. In this study we compared a novel blood collection device against traditional K3EDTA tubes for its ability to stabilize cfRNA in blood when subjected to conditions that can occur during sample storage and shipping.
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The Elusive Structure of Pd2(dba)3. Examination by Isotopic Labeling, NMR Spectroscopy, and X-ray Diffraction Analysis: Synthesis and Characterization of Pd2(dba-Z)3 Complexes.
J. Am. Chem. Soc.
PUBLISHED: 05-23-2013
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Pd(0)2(dba)3 (dba = E,E-dibenzylidene acetone) is the most widely used Pd(0) source in Pd-mediated transformations. Pd(0)2(dba-Z)3 (Z = dba aryl substituents) complexes exhibit remarkable and differential catalytic performance in an eclectic array of cross-coupling reactions. The precise structure of these types of complexes has been confounding, since early studies in 1970s to the present day. In this study the solution and solid-state structures of Pd(0)2(dba)3 and Pd(0)2(dba-Z)3 have been determined. Isotopic labeling ((2)H and (13)C) has allowed the solution structures of the freely exchanging major and minor isomers of Pd(0)2(dba)3 to be determined at high field (700 MHz). DFT calculations support the experimentally determined major and minor isomeric structures, which show that the major isomer of Pd(0)2(dba)3 possesses bridging dba ligands found exclusively in a s-cis,s-trans conformation. For the minor isomer one of the dba ligands is found exclusively in a s-trans,s-trans conformation. Single crystal X-ray diffraction analysis of Pd(0)2(dba)3·CHCl3 (high-quality data) shows that all three dba ligands are found over two positions. NMR spectroscopic analysis of Pd(0)2(dba-Z)3 reveals that the aryl substituent has a profound effect on the rate of Pd-olefin exchange and the global stability of the complexes in solution. Complexes containing the aryl substituents, 4-CF3, 4-F, 4-t-Bu, 4-hexoxy, 4-OMe, exhibit well-resolved (1)H NMR spectra at 298 K, whereas those containing 3,5-OMe and 3,4,5-OMe exhibit broad spectra. The solid-state structures of three Pd(0)2(dba-Z)3 complexes (4-F, 4-OMe, 3,5-OMe) have been determined by single crystal X-ray diffraction methods, which have been compared with Goodsons X-ray structure of Pd(0)2(dba-4-OH)3.
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Imputation-based meta-analysis of severe malaria in three African populations.
PLoS Genet.
PUBLISHED: 05-01-2013
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Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic diversity, both within and between populations, is far more extensive. We analyse genome-wide data from approximately 5,000 individuals with severe malaria and 7,000 population controls from three different locations in Africa. Our results show that the standard approach is well powered to detect known malaria susceptibility loci when sample sizes are large, and that modern methods for association analysis can control the potential confounding effects of population structure. We show that pattern of association around the haemoglobin S allele differs substantially across populations due to differences in haplotype structure. Motivated by these observations we consider new approaches to association analysis that might prove valuable for multicentre GWAS in Africa: we relax the assumptions of SNP-based fixed effect analysis; we apply Bayesian approaches to allow for heterogeneity in the effect of an allele on risk across studies; and we introduce a region-based test to allow for heterogeneity in the location of causal alleles.
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Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway.
Cell
PUBLISHED: 04-12-2013
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The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patients life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohns disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGF?1 reduces production of proinflammatory cytokines, including TNF?, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.
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The outlook for alemtuzumab in multiple sclerosis.
BioDrugs
PUBLISHED: 04-06-2013
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Alemtuzumab is a humanized anti-CD52 monoclonal antibody. Treatment in humans results in a rapid, profound, and prolonged B- and T-cell lymphopenia. Subsequently, lymphocyte reconstitution by homeostatic mechanisms alters the composition, phenotype, and function of T-cell subsets, thus allowing the immune system to be reset. One phase II and two phase III randomized, multicenter, single-blinded (outcomes assessor) clinical trials of alemtuzumab in relapsing-remitting multiple sclerosis have now been completed. Against an active comparator and the current first-line therapy for relapsing-remitting multiple sclerosis (interferon-beta), alemtuzumab showed a significant reduction in annualized relapse rate as well as a significant reduction in the accumulation of disability. These outcomes are sustained over at least 5 years following treatment. The most common adverse effects are mild infusion reactions, an increased incidence of mild-to-moderate severity infections and secondary autoimmunity. The latter is observed in a third of treated patients, commonly thyroid disease but other target cells have been described including cytopenias. Marketing authorization applications have been submitted for the use of alemtuzumab in multiple sclerosis to the Food and Drug Administration and the European Medicines Agency, with licensing expected in 2013. Here, we discuss the outlook for alemtuzumab in multiple sclerosis in light of the currently available therapies, outcomes of and lessons learnt from clinical trials, and the overall position of monoclonal antibodies in modern treatment strategies.
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The distribution of haemoglobin C and its prevalence in newborns in Africa.
Sci Rep
PUBLISHED: 04-02-2013
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Haemoglobin C (HbC) is one of the commonest structural haemoglobin variants in human populations. Although HbC causes mild clinical complications, its diagnosis and genetic counselling are important to prevent inheritance with other haemoglobinopathies. Little is known about its contemporary distribution and the number of newborns affected. We assembled a global database of population surveys. We then used a Bayesian geostatistical model to create maps of HbC frequency across Africa and paired our predictions with high-resolution demographics to calculate heterozygous (AC) and homozygous (CC) newborn estimates and their associated uncertainty. Data were too sparse outside Africa for this methodology to be applied. The highest frequencies were found in West Africa but HbC was commonly found in other parts of the continent. The expected annual numbers of AC and CC newborns in Africa were 672,117 (interquartile range (IQR): 642,116-705,163) and 28,703 (IQR: 26,027-31,958), respectively. These numbers are about two times previous estimates.
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Online biomedical resources for malaria-related red cell disorders.
Hum. Mutat.
PUBLISHED: 04-01-2013
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Warnings about the expected increase of the global public health burden of malaria-related red cell disorders are accruing. Past and present epidemiological data are necessary to track spatial and temporal changes in the frequencies of these genetic disorders. A number of open access biomedical databases including data on malaria-related red cell disorders have been launched over the last two decades. Here, we review the content of these databases, most of which focus on genetic diversity, and we describe a new epidemiological resource developed by the Malaria Atlas Project. To tackle upcoming public health challenges, the integration of epidemiological and genetic data is important. As many countries are considering implementing national screening programs, strategies to make such data more accessible are also needed.
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A review of trends in attrition rates for surgical faculty: a case for a sustainable retention strategy to cope with demographic and economic realities.
J. Am. Coll. Surg.
PUBLISHED: 03-21-2013
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Our aim was to compare trends in retention of academic surgeons by reviewing surgical faculty attrition rates (leaving academic surgery for any reason) of 3 cohorts at 5-year intervals between 1996 and 2011.
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The genetic risk of acute seizures in African children with falciparum malaria.
Epilepsia
PUBLISHED: 03-06-2013
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It is unclear why some children with falciparum malaria develop acute seizures and what determines the phenotype of seizures. We sought to determine if polymorphisms of malaria candidate genes are associated with acute seizures.
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Modelling metabolic CO? evolution--a fresh perspective on respiration.
Plant Cell Environ.
PUBLISHED: 03-06-2013
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Respiration is a major contributor to net exchange of CO? between plants and the atmosphere and thus an important aspect of the vegetation component of global climate change models. However, a mechanistic model of respiration is lacking, and so here we explore the potential for flux balance analysis (FBA) to predict cellular CO? evolution rates. Metabolic flux analysis reveals that respiration is not always the dominant source of CO?, and that metabolic processes such as the oxidative pentose phosphate pathway (OPPP) and lipid synthesis can be quantitatively important. Moreover, there is considerable variation in the metabolic origin of evolved CO? between tissues, species and conditions. Comparison of FBA-predicted CO? evolution profiles with those determined from flux measurements reveals that FBA is able to predict the metabolic origin of evolved CO? in different tissues/species and under different conditions. However, FBA is poor at predicting flux through certain metabolic processes such as the OPPP and we identify the way in which maintenance costs are accounted for as a major area of improvement for future FBA studies. We conclude that FBA, in its standard form, can be used to predict CO? evolution in a range of plant tissues and in response to environment.
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A method for accounting for maintenance costs in flux balance analysis improves the prediction of plant cell metabolic phenotypes under stress conditions.
Plant J.
PUBLISHED: 03-03-2013
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Flux balance models of metabolism generally utilize synthesis of biomass as the main determinant of intracellular fluxes. However, the biomass constraint alone is not sufficient to predict realistic fluxes in central heterotrophic metabolism of plant cells because of the major demand on the energy budget due to transport costs and cell maintenance. This major limitation can be addressed by incorporating transport steps into the metabolic model and by implementing a procedure that uses Pareto optimality analysis to explore the trade-off between ATP and NADPH production for maintenance. This leads to a method for predicting cell maintenance costs on the basis of the measured flux ratio between the oxidative steps of the oxidative pentose phosphate pathway and glycolysis. We show that accounting for transport and maintenance costs substantially improves the accuracy of fluxes predicted from a flux balance model of heterotrophic Arabidopsis cells in culture, irrespective of the objective function used in the analysis. Moreover, when the new method was applied to cells under control, elevated temperature and hyper-osmotic conditions, only elevated temperature led to a substantial increase in cell maintenance costs. It is concluded that the hyper-osmotic conditions tested did not impose a metabolic stress, in as much as the metabolic network is not forced to devote more resources to cell maintenance.
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Gender differences in substance use treatment utilization in the year prior to deployment in Army service members.
J Subst Abuse Treat
PUBLISHED: 02-24-2013
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Although military men have heavier drinking patterns, military women experience equal or higher rates of dependence symptoms and similar rates of alcohol-related problems as men at lower levels of consumption. Thus, gender may be important for understanding substance use treatment (SUT) utilization before deployment. Military health system data were analyzed to examine gender differences in both substance use diagnosis (SUDX) and SUT in 152,447 Army service members returning from deployments in FY2010. Propensity score analysis of probability of SUDX indicated that women had lower odds (AOR: 0.91, 95% CI: 0.86-0.96) of military lifetime SUDX. After adjusting for lifetime SUDX using propensity score analysis, multivariate regression found women had substantially lower odds (AOR: 0.61; 95% CI: 0.54-0.70) of using SUT the year prior to deployment. Findings suggest gender disparities in military-provided SUT and a need to consider whether military substance use assessment protocols are sensitive to gender differences.
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Laser ablative surface treatment for enhanced bonding of Ti-6Al-4V alloy.
ACS Appl Mater Interfaces
PUBLISHED: 02-05-2013
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Adhesive bonding offers many advantages over mechanical fastening, but requires certification before it can be incorporated in primary structures for commercial aviation without disbond-arrestment features or redundant load paths. Surface preparation is widely recognized as the key step to producing robust and predictable adhesive bonds. Surface preparation by laser ablation provides an alternative to the expensive, hazardous, polluting, and less precise practices used currently such as chemical-dip, manual abrasion and grit blast. This report documents preliminary testing of a surface preparation technique using laser ablation as a replacement for the chemical etch and abrasive processes currently applied to Ti-6Al-4V alloy adherends. Surface roughness and surface chemical composition were characterized using interference microscopy and X-ray photoelectron spectroscopy, respectively. A technique for fluorescence visualization was developed which allowed for quantitative failure mode analysis. Wedge crack extension testing in a hot, humid environment indicated the relative effectiveness of various surface treatments. Increasing ablation duty cycle reduced crack propagation and adhesive failure. Single lap shear testing showed an increase in strength and durability as laser ablation duty cycle and power were increased. Chemical analyses showed trends for surface chemical species, which correlated with improved bond strength and durability.
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Determinants of anemia among preschool children in rural, western Kenya.
Am. J. Trop. Med. Hyg.
PUBLISHED: 02-04-2013
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Although anemia in preschool children is most often attributed to iron deficiency, other nutritional, infectious, and genetic contributors are rarely concurrently measured. In a population-based, cross-sectional survey of 858 children 6-35 months of age in western Kenya, we measured hemoglobin, malaria, inflammation, sickle cell, ?-thalassemia, iron deficiency, vitamin A deficiency, anthropometry, and socio-demographic characteristics. Anemia (Hb < 11 g/dL) and severe anemia (Hb < 7 g/dL) prevalence ratios (PRs) for each exposure were determined using multivariable modeling. Anemia (71.8%) and severe anemia (8.4%) were common. Characteristics most strongly associated with anemia were malaria (PR: 1.7; 95% confidence interval [CI] = 1.5-1.9), iron deficiency (1.3; 1.2-1.4), and homozygous ?-thalassemia (1.3; 1.1-1.4). Characteristics associated with severe anemia were malaria (10.2; 3.5-29.3), inflammation (6.7; 2.3-19.4), and stunting (1.6; 1.0-2.4). Overall 16.8% of anemia cases were associated with malaria, 8.3% with iron deficiency, and 6.1% with inflammation. Interventions should address malaria, iron deficiency, and non-malarial infections to decrease the burden of anemia in this population.
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Quality of cancer survivorship care in the military health system (TRICARE).
Cancer J
PUBLISHED: 01-23-2013
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Following the acute phase of treatment, national guidelines recommend cancer survivors have routine contact with health care providers and undergo basic ancillary testing while avoiding high-cost imaging (HCI). We conducted this study to determine how frequently breast, prostate, and colorectal cancer survivors received recommended follow-up care and HCI tests during the survivorship period.
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Military report more complementary and alternative medicine use than civilians.
J Altern Complement Med
PUBLISHED: 01-16-2013
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The study objective was to estimate complementary and alternative medicine (CAM) use among active duty military and compare data with civilian use.
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Engineered quorum sensing using pheromone-mediated cell-to-cell communication in Saccharomyces cerevisiae.
ACS Synth Biol
PUBLISHED: 01-07-2013
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Population-density-dependent control of gene expression, or quorum sensing, is widespread in nature and is used to coordinate complex population-wide phenotypes through space and time. We have engineered quorum sensing in S. cerevisiae by rewiring the native pheromone communication system that is normally used by haploid cells to detect potential mating partners. In our system, populations consisting of only mating type "a" cells produce and respond to extracellular ?-type pheromone by arresting growth and expressing GFP in a population-density-dependent manner. Positive feedback quorum sensing dynamics were tuned by varying ?-pheromone production levels using different versions of the pheromone-responsive FUS1 promoter as well as different versions of pheromone genes (mf?1 or mf?2). In a second system, pheromone communication was rendered conditional upon the presence of aromatic amino acids in the growth medium by controlling ?-pheromone expression with the aromatic amino acid responsive ARO9 promoter. In these circuits, pheromone communication and response could be fine-tuned according to aromatic amino acid type and concentration. The genetic control programs developed here are responsive to dynamic spatiotemporal and chemical cellular environments, resulting in up-regulation of gene expression. These programs could be used to control biochemical pathways for the production of fuels and chemicals that are toxic or place a heavy metabolic burden on cell growth.
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Consulting communities on feedback of genetic findings in international health research: sharing sickle cell disease and carrier information in coastal Kenya.
BMC Med Ethics
PUBLISHED: 01-04-2013
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International health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants perspectives, including social forms of benefit and harm, and the influence of access to care. To inform research practice locally, and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status.
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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.

Video X seems to be unrelated to Abstract Y...

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.