Comparing research investment to United Kingdom institutions and published outputs for tuberculosis, HIV and malaria: A systematic analysis across 1997-2013

Background: The "Unfinished Agenda" of infectious diseases is of great importance to policymakers and research funding agencies that require ongoing research evidence on their effective management. Journal publications help effectively share and disseminate research results to inform policy and practice. We assess research investments to United Kingdom institutions in HIV, tuberculosis and malaria, and analyse these by numbers of publications and citations and by disease and type of science. Methods: Information on infection-related research investments awarded to United Kingdom institutions across 1997-2010 were sourced from funding agencies and individually categorised by disease and type of science. Publications were sourced from the Scopus database via keyword searches and filtered to include only publications relating to human disease and containing a United Kingdom-based first and/or last author. Data were matched by disease and type of science categories. Investment (United Kingdom pounds) and publications were compared to generate an 'investment per publication' metric; similarly, an 'investment per citation' metric was also developed as a measure of the usefulness of research. Results: Total research investment for all three diseases was £1.4 billion, and was greatest for HIV (£651.4 million), followed by malaria (£518.7 million) and tuberculosis (£239.1 million). There were 17,271 included publications, with 9,322 for HIV, 4,451 for malaria, and 3,498 for tuberculosis. HIV publications received the most citations (254,949), followed by malaria (148,559) and tuberculosis (100,244). According to UK pound per publication, tuberculosis (£50,691) appeared the most productive for investment, compared to HIV (£61,971) and malaria (£94,483). By type of science, public health research was most productive for HIV (£27,296) and tuberculosis (£22,273), while phase I-III trials were most productive for malaria (£60,491). According to UK pound per citation, tuberculosis (£1,797) was the most productive area for investment, compared to HIV (£2,265) and malaria (£2,834). Public health research was the most productive type of science for HIV (£2,265) and tuberculosis (£1,797), whereas phase I-III trials were most productive for malaria (£1,713). Conclusions: When comparing total publications and citations with research investment to United Kingdom institutions, tuberculosis research appears to perform best in terms of efficiency. There were more public health-related publications and citations for HIV and tuberculosis than other types of science. These findings demonstrate the diversity of research funding and outputs, and provide new evidence to inform research investment strategies for policymakers, funders, academic institutions, and healthcare organizations.Infectious Disease Research Networ

The protective effect of ischemic preconditioning on rat testis

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Midwest Quarterly; Vol. 17 No. 3

GENE E. VOLLEN, who is the most recent addition to our Board of Editors, did his undergraduate work at Michigan State University and received his Ph. D. in musicology from North Texas State University. He is associate professor of music at KSCP. LAMAR YORK, who investigates the authorship of the earliest English secular lyrics, teaches English at DeKalb College in Atlanta and is working on his doctorate at Emory University. T. MILDRED WHERRITT, who writes about marriage proposals in Austen\u27s novels, is a graduate student at Wichita State University. She has published a number of poems. EUGÉNIE LAMBERT HAMNER, who finds affirmations in Willa Cather\u27s A Lost Lady, received her Ph. D. from the University of North Carolina and teaches English at the University of South Alabama. BARBARA MELDRUM, who examines the images of women in western fiction, received her Ph. D. from Claremont Graduate School and is professor of Engilsh at the University of Idaho. Her articles on American literature have appeared in several journals. DAVID E. ZEHR, who writes about Hemingway\u27s politics in For Whom the Bell Tolls, teaches English at California State University at Los Angeles and is completing his dissertation at Indiana University. ARTHUR A. EKIRCH, JR., who reexamines the Eisenhower and Kennedy administrations, is professor of history at the State University of New York at Albany. He has published six books on American intellectual history. TOMAS O\u27LEARY, whose work has appeared in these pages from time to time since October 1970, has given us a selection of poems from his new book, Fool at the Funeral (Lynx House Press, Box 300, Amherst, Mass. 01002). He lives in Cambridge and keeps away from po-biz, which means he has never wrestled himself a grant or a residency

Effects of Antiepileptic Drugs on GABA Responses and on Reduction of GABA Responses by PTZ and DMCM on Mouse Neurons in Cell Culture

The mechanisms of action of antiepileptic drugs effective against generalized absence seizures (antiabsence AEDs) remain uncertain. Antiabsence AEDs are generally effective against seizures induced in experimental animals by pentylenÉtÉtrazol (PTZ) and methyl-6,7-dimethoxy-4-ethyl-Β-carboline-3-carboxylate (DMCM), drugs which reduce GABAergic inhibition. Thus, antiabsence AEDs have been suggested to enhance GABAergic inhibition. We studied the effects of several AEDs on GABA responses recorded from mouse spinal cord neurons grown in primary dissociated cell culture. Four antiabsence AEDs were included: ethosuximide (ESM), dimethadione (DMO), sodium valproate (VPA), and diazepam (DZP). Two experimental AEDs, CGS 9896 and ZK 91296, with anticonvulsant action against PTZ- or DMCM-induced seizures were also included. Possible effects of the antiabsence and experimental AEDS on PTZ- and DMCM-induced inhibition of GABA responses were also evaluated. PTZ and DMCM revers-ibly reduced GABA responses in a concentration-dependent manner. PTZ complÉtÉly inhibited GABA responses at 10 mM (IC 50 of 1.1 mM), whereas DMCM-induced inhibition of GABA responses reached a plateau level of 39% of control values at 1 p.M (IC 50 of 33 nM). ESM (1,200 ΜM), DMO (6 mM), VPA (200 u.M), CGS 9896 (2 ΜM), and ZK 98% (2 Μ M ) did not alter GABA responses. DZP enhanced GABA responses in a concentration-dependent manner. The inhibition of GABA responses produced by PTZ 1 mM was unaltered by ESM (600 Μ M ), DMO (6 mM), CGS 9896 (1 Μ M), or ZK 9896 (1 ΜM)- Coapplication of VPA (200 ΜM) and PTZ (1 mM) slightly enhanced the PTZ effect. DZP (> 10 nM), however, reversed the PTZ-induced reduction of GABA responses. The DMCM (250 nM) inhibition of GABA-responses was unaltered by ESM (600 Μ.M), DMO (2 mM), or VPA (200 ΜM). CGS 9896 (2 Μ M ) and ZK 91296 (2 ΜM), however, antagonized the DMCM effect. DZP (> 10 nM) significantly reversed the DMCM-induced inhibition of GABA responses. The lack of effect of VPA, ESM, and DMO on postsynaptic GABA responses suggests that direct enhancement of postsynaptic GABA action is not a common mechanism of action of antiabsence AEDs. The AEDs DZP, CGS 98%, and ZK 912% all reversed DMCM, but not PTZ, reduction of GABA responses, suggesting that these AEDs blocked DMCM seizures by acting at benzodiazepine receptors. However, since only DZP enhanced GABA responses, it is unclear how CGS 98% and ZK 912% blocked PTZ seizures. Key Words: Anticonvulsants–GABA–Neuron culture–Cell culture–Spinal cord neurons–Convulsants. RESUMEN Los mecanismos de accidn de las medicaciones antiepilÉpticas eficaces contra los ataques generalizados de ausencia (AEDs antiausencia) permanecen inciertos. Los AEDs antiausencia son, generalmente, eficaces contra ataques experimentales inducidos por el pentilentetrazol (PTZ) y el metil-6,7-dimetoxy-4-etil-Pcarbolina-3-carboxilato (DMCM) en animates, medicaciones que reducen la inhibiciÓn GABAÉrgica. Hemos estudiado los efectos de varios AEDs sobre respuestas-GABA registradas en las neuronas de la mÉdula espinal de ratones que habian crecido en cultivos de cÉlulas primarieas disociadas. Cuatro AEDs antiausencia fueron incluidos: etoxusimida (ESM), dimetadiona (DMO), valproato sÓdico (VPA) y diazepan (DZP). TambtÉn se incluyeron dos AEDs experimentales, CGS 9896 y ZK 912%, con acciÓn anticonvulsiva contra los ataques inducidos por PTZ o DMCM. TambiÓn se valoraron los posibles efectos de los AEDs antiausencia y experimentales sobre el PTZ y la inhibiciÓn de las respuestas-GABA inducidas por el DMCM. El PTZ y el DMCM redujeron las respuestas-GABA de modo reversible y dependiendo de sus concentraciones. El PTZ inhibiÓ cmpleta-mente las respuestas-GABA a 10 mM (IC 50 de 1.1 mM) mientras que la inhibitiÓn de las respuestas GABA inducida por el DMCM alcanzÓ un nivel estable del 39% de los valores control con 1 Μ. M (IC 50 de 33 mM). La ESM (1200 Μ.M), la DMO (6 mM), el VPA (200 Μ M ), el CGS 98% (2 Μ M) y el ZK 98% (2 Μ M) no alteraron las respuestas-GABA. El DZP aumentÓ las respuestas GABA de una manera concentraciÓn-dependiente. La inhibition de las respuestas-GABA producidas por el PTZ (1 mM), no se altero con las ESM (600 Μ M), la DMO (6 mM), el CGS 98% (1 Μ M) o el ZK 98% (1 Μ .M). La co-aplicacion de VPA (200 Μ M) y el PTZ (1 mM) aument6 ligeramente los efectos del PTZ. Sin embargo el DZP (10 nM) revirtiÓ significativamente la inhibition de las respuestas GABA inducidas por el DMCM. La falta de efectos de CPA, ESM y DMO sobre las respuestas GABA post-sinÁpticas sugiere que el incremento de la acciÓn GABA post-sinÁptica no es un mecanismo comÚn de actuatiÓn de las AEDs antiausencia. Todas las AEDs DZP, CGS 98% y ZK 912% revirtieron la reduction de las respuestas GABA producidas por el DMCM pero no las inducidas por el PTZ lo que sugiere que estos AEDs bloquean los ataques DMCM actuando sobre los receptores de la benzodiazepina. Sin embargo, puesto que el incremento de las respuestas GABA sÓlÓ se produce por el DZP, permanece todavia sin aclarar el por quÉ el CGS 98% y el ZK 912% bloquean los ataques producidos por el PTZ. ZUSAMMENFASSUNG Der Wirkmechansimus von Antiepileptika gegen generalisierte Absencen ist unklar. Antiabsencemittel sind generell wirkungs-voll gegen PTZ- und Methyl-6,7-Dimethoxy-4-Äthyl-P-Carbolin-Β-Carboxylat (DMCM) induzierte tierexperimentelle AnfÄlle, also von Medikamenten, die die GABA-erge Inhibition reduzieren. Es wurde vermutet, daß Antiabsencemittel die GABA-erge Inhibition verstÄrken. Wir untersuchten die Wirkung von verschiedenen Antiepileptika auf GABA-Antworten in spinalen MÄuseneuronen, die in Zellkulturen gew-achsen waren. Es wurden 4 Absencemittel untersucht: Ethosux-imid (ESM), Dimethadion (DMD), Sodium Valproat (VPA) und Diazepam (DZP). ZusÄtzlich wurden 2 experimentelle Antiepileptika, CGS 98% und ZK 912%, die gegen PTZ0 oder DMCM-induzierte AnfÄlle wirkungsvoll sind, eingeschlossen. Mogliche Wirkungen der Antiabsence- und experimentellen Antiepileptika auf PTZ- und DMCM-induzierte Hemmung der GABA-Antworten wurden ebenfalls ausgewertet. PTZ und DMCM zeigten eine konzentrationsabhÄngige reversible Reduktion der GABA-Antworten. PTZ zeigte eine komplette Hemmung der GABA-Antworten bei 10 mM (IC 50 1,1 mM), DMCM-Hemmung der GABA-Antworten zeigte ein Plateau von 39% der Kontroll-werte bei 1 uJtf (ICJO von 33 mAfl. ESM (1200 uJtf), DMD (6 mM), VPA (200 Μ M), CGS 98% (2 Μ M) und ZK 98% (2 Μ M) anderten nicht die GABA-Antworten. DZP verstarkte die GABA-Antworten konzentrationsabhangig. Die durch PTZ (1 mM) hervorgerufene Hemmung der GABA-Antworten war bei ESM (600 Μ M), DMD (6 mM), CGS 98% (1 mAO und ZK 3836 (1 mM) unverÄndert. ZusÄtliche Anwendung von VPA (200 mM) und PTZ (1 mM) verstÄrkten geringfÜgig den PTZ-Effekt. DZP (10 nM) kehrte die durch PTZ hervorgerufene Reduktion der GABA-Antworten um. Die durch DMCM (250 nM) hervorgerufene Hemmung der GABA-Antworten war durch ESM (600 Μ .M), DMD (2 mM) und VPA (200 Μ M ) unbeeinflusst. CGS 98% (2 Μ M) und ZK 912% (2 Μ M ) antagonisierten die DMCM-Wirkung. DZP (>10 nM) kehrte die durch DMCM-induzierte Hemmung der GABA-Antworten um. Das Fehlen einer Wirkung von VPA. ESM und DMD auf die postsynaptischen GABA-Antworten legen nahe, daß eine direkte VerstÄrkung der postsynaptischen GABA-Aktion kein gemeinsamer Mechanis-mus der Antiabsencemittel darstellt. Die Antiepileptika DZP, CGS 98% und ZK 912% kehrten die DMCM-Wirkung auf die GABA-Antworten um, jedoch nicht die von PTZ, was vermuten lapt, daß diese Antiepileptika die DMCM-AnfÄlle Über die Wirkung an den Benzodiazipin-Rezeptoren verhinderte. Da jedoch nur DZP GABA-Antworten verstarkte, ist unklar, in welcher Weise CGS 98% und ZK 912% die PTZ-AnfaUe ver-hinderten.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65188/1/j.1528-1157.1989.tb05275.x.pd

Prospective randomized study comparing the Teleflex Medical SaphLITE Retractor to the Ethicon CardioVations Clearglide Endoscopic System

BACKGROUND: Several minimally invasive saphenous vein harvesting techniques have been developed to reduce morbidities associated with coronary artery bypass grafting. This prospective, randomized study was designed to compare two commonly used minimally invasive saphenous vein harvesting techniques, the SaphLITE Retractor System (Teleflex Medical) and the Clearglide Endoscopic Vessel Harvesting System (Ethicon CardioVations, Inc.). METHODS: Between January 2003 and March 2004, a total of 200 patients scheduled for primary, nonemergent coronary artery bypass grafting, with or without concomitant procedures were randomized into two groups: SaphLITE (n = 100) and Clearglide (n = 100). Pre-, intra- and postoperative data was collected and subjected to statistical analysis. Randomization provided homogenous groups with respect to preoperative risk factors. RESULTS: Harvest location for the SaphLITE group was thigh (n = 40), lower leg (n = 5) and both lower leg and thigh (n = 55). The location of harvest for the Clearglide group was thigh (n = 3), lower leg (n = 16) and both lower leg and thigh (n = 81). The mean incision length was 3.6 cm (range, 2–6) in the SaphLITE group versus 2.1 cm (range, 1–4) in the Clearglide group (p < 0.05). The total incision length was 12.9 cm versus 8.9 (p < 0.05) in the SaphLITE and Clearglide groups. Conversion to the open technique occurred in 5 SaphLITE patients and 7 Clearglide patients. Intraoperative leg exploration for bleeding occurred in two of the Clearglide patients and none of the SaphLITE patients. Post-operative complications specifically related to minimally invasive harvesting technique, including a two-week post-discharge visit, were not statistically different between the groups. CONCLUSION: The saphenous vein can be safely harvested utilizing the SaphLITE and Clearglide systems. While the Clearglide system allows for fewer incisions (number and length) and less harvest time, these benefits may be outweighed by the increased cost of the Clearglide system compared to the SaphLITE retractor

Natural Variation in the Thermotolerance of Neural Function and Behavior due to a cGMP-Dependent Protein Kinase

Although it is acknowledged that genetic variation contributes to individual differences in thermotolerance, the specific genes and pathways involved and how they are modulated by the environment remain poorly understood. We link natural variation in the thermotolerance of neural function and behavior in Drosophila melanogaster to the foraging gene (for, which encodes a cGMP-dependent protein kinase (PKG)) as well as to its downstream target, protein phosphatase 2A (PP2A). Genetic and pharmacological manipulations revealed that reduced PKG (or PP2A) activity caused increased thermotolerance of synaptic transmission at the larval neuromuscular junction. Like synaptic transmission, feeding movements were preserved at higher temperatures in larvae with lower PKG levels. In a comparative assay, pharmacological manipulations altering thermotolerance in a central circuit of Locusta migratoria demonstrated conservation of this neuroprotective pathway. In this circuit, either the inhibition of PKG or PP2A induced robust thermotolerance of neural function. We suggest that PKG and therefore the polymorphism associated with the allelic variation in for may provide populations with natural variation in heat stress tolerance. for's function in behavior is conserved across most organisms, including ants, bees, nematodes, and mammals. PKG's role in thermotolerance may also apply to these and other species. Natural variation in thermotolerance arising from genes involved in the PKG pathway could impact the evolution of thermotolerance in natural populations

Pragmatic Evaluation of an Improvement Program for People Living With Modifiable High-Risk COPD Versus Usual Care: Protocol for the Cluster Randomized PREVAIL Trial

Background: The burden of chronic obstructive pulmonary disease (COPD) is well established, but opportunities for earlier diagnosis and improved management are still missed. Compared to the general COPD population, patients with a history of exacerbations and suboptimal treatment (“modifiable high-risk”) are at greater risk of future exacerbations and adverse health outcomes. To date there is no systematic approach for identifying and treating this patient group. Methods: Two cluster randomized controlled trials (CRTs) in the United Kingdom and United States will assess the impact of a primary care-based quality improvement program (COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care [CONQUEST]), compared to routine care. In each trial, 126 primary care clusters will be randomized 1:1 to intervention or control arms. Three groups of modifiable high-risk patients will be identified using electronic medical records: undiagnosed with potential COPD, newly diagnosed COPD, and already diagnosed COPD. Eligible patients will be aged ≥40 years, have experienced ≥2 moderate/≥1 severe exacerbation(s) in the prior 24 months, including ≥1 in the last 12 months, and not be prescribed inhaled triple therapy. Patients in the undiagnosed group will also be required to have a positive smoking history. Primary trial outcomes will be the annual rate of exacerbations and the annual rate of major adverse cardiac or respiratory events, comparing the quality improvement program against routine care. Discussion: These will be the first CRTs assessing such a comprehensive primary care-based COPD quality improvement program. Intention-to-treat analysis of trial outcomes after 24 months will inform its effectiveness in targeting the identification, assessment, treatment, and follow-up of patients with modifiable high-risk COPD

Crop Updates 2010 - Crop Specific

This session covers twenty four papers from different authors: PLENARY 1. Challenges facing western Canadian cropping over the next 10 years, Hugh J Beckie, Research Centre, Agriculture and Agri-Food Canada, Saskatoon, Saskatchewan CROP SPECIFIC Breeding 2. The challenge of breeding canola hybrids – new opportunities for WA growers, Wallace Cowling, Research Director, Canola Breeders Western Australia Pty Ltd 3. Chickpea 2009 crop variety testing of germplasm developed by DAFWA/CLIMA/ICRISAT/COGGO alliance. Khan, TN1,3, Adhikari, K1,3, Siddique, K2, Garlinge, J1, Smith, L1, Morgan, S1 and Boyd, C1 1Department of Agriculture and Food, Western Australia (DAFWA), 2Insititute of Agriculture, The University of Western Australia (UWA), 3Centre for Legumes in Mediterranean Agriculture (CLIMA), The University of Western Australia 4. PBA Pulse Breeding Australia – 2009 Field Pea Results, Ian Pritchard1, Chris Veitch1, Colin Boyd1, Stuart Morgan1, Alan Harris1 and Tony Leonforte2, 1Department of Agriculture and Food, Western Australia, 2Department of Primary Industries, Victoria 5. PBA Pulse Breeding Australia – 2009 Chickpea Results, Ian Pritchard1, Chris Veitch1, Colin Boyd1, Murray Blyth1, Shari Dougal1 and Kristy Hobson2 1Department of Agriculture and Food, Western Australia, 2Department of Primary Industries, Victoria Decision Support 6. A tool for identifying problems in wheat paddocks, Ben Curtis and Doug Sawkins, Department of Agriculture and Food 7. DAFWA Seasonal Forecast for 2010, Stephens, D, Department of Agriculture and Food, Western Australian, Climate and Modelling Group Disease 8. Enhancement of black spot resistance in field pea, Kedar Adhikari, T Khan, S Morgan and C Boyd, Department of Agriculture and Food, 9. fungicide management of yellow spot in wheat, Ciara Beard, Kith Jayasena, Kazue Tanaka and Anne Smith, Department of Agriculture and Food 10. Resistance to infection by Beet western yellows virus in four Australian canola varieties, Brenda Coutts and Roger Jones, Department of Agriculture and Food 11. Yellow spot carryover risk from stubble in wheat-on-wheat rotations, Jean Galloway, Pip Payne and Tess Humphreys, Department of Agriculture and Food 12. Fungicides for the future: Management of Barley Powdery Mildew and Leaf Rust, Kith Jayasena, Kazue Tanaka and William MacLeod, Department of Agriculture and Food 13. 2009 canola disease survey and management options for blackleg and Sclerotinia in 2010, Ravjit Khangura, WJ MacLeod, M Aberra and H Mian, Department of Agriculture and Food 14. Impact of variety and fungicide on carryover of stubble borne inoculum and yellow spot severity in continuous wheat cropping, Geoff Thomas, Pip Payne, Tess Humphreys and Anne Smith, Department of Agriculture and Food 15. Limitations to the spread of Wheat streak mosaic virus by the Wheat curl mite in WA during 2009, Dusty Severtson, Peter Mangano, Brenda Coutts, Monica Kehoe and Roger Jones, Department of Agriculture and Food 16. Viable solutions for barley powdery mildew, Madeline A. Tucker, Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University Marketing 17. The importance of varietal accreditation in a post-deregulation barley marketing environment, Neil Barker, Barley Australia 18. Can Australia wheat meet requirements for a new middle east market? Robert Loughman, Larisa Cato, Department of Agriculture and Food, and Ken Quail, BRI Australia VARIETY PERFORMANCE 19. Sowing rate and time for hybrid vs open-pollinated canola, Mohammad Amjad and Mark Seymour, Department of Agriculture and Food 20. HYOLA® National Hybrid vs OP Canola Hybrid F1 vs Retained Seed Generation Trial Results and recommendations for growers, Justin Kudnig, Mark Thompson, Anton Mannes, Michael Uttley, Chris Fletcher, Andrew Etherton, Nick Joyce and Kate Light, Pacific Seeds Australia 21. HYOLA® National Hybrid vs OP Canola Sowing Rate Trial Results and plant population recommendations for Australian growers, Justin Kudnig, Mark Thompson, Anton Mannes, Michael Uttley, Andrew Etherton, Chris Fletcher, Nick Joyce and Kate Light, Pacific Seeds Australia; Peter Hamblin, Agritech Research Young, NSW, Michael Lamond, Agrisearch, York, Western Australia 22. Desi chickpea agronomy for 2010, Alan Meldrum, Pulse Australia and Wayne Parker, Department of Agriculture and Food 23. New wheat varieties – exploit the benefits and avoid the pitfalls, Steve Penny, Sarah Ellis, Brenda Shackley, Christine Zaicou, Shahajahan Miyan, Darshan Sharma and Ben Curtis, Department of Agriculture and Food 24. The influence of genetics and environment on the level of seed alkaloid in narrow-leafed lupins, Greg Shea1, Bevan Buirchell1, David Harris2 and Bob French1, 1Department of Agriculture and Food, 2ChemCentr