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5. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes

Author

Momozawa, Y. (Yukihide), Dmitrieva, J. (Julia), Théâtre, E. (Emilie), Deffontaine, V. (Valérie), Rahmouni, S. (Souad), Charloteaux, B. (Benoît), Crins, F. (François), Docampo, E. (Elisa), Elansary, M. (Mahmoud), Gori, A.-S. (Ann-Stephan), Lecut, C. (Christelle), Mariman, R. (Rob), Mni, M. (Myriam), Oury, C. (Cécile), Altukhov, I. (Ilya), Alexeev, D. (Dmitry), Aulchenko, Y.S. (Yurii), Amininejad, L. (Leila), Bouma, G. (Gerd), Hoentjen, F., Löwenberg, M., Oldenburg, B. (Bas), Pierik, M. (Marieke), Vander Meulen-De Jong, A.E. (Andrea E.), Woude, C.J. (Janneke) van der, Visschedijk, M. (Marijn), Lathrop, M. (Mark), Hugot, J.P. (J.), Weersma, R.K. (Rinse), De Vos, M. (Martine), Franchimont, D. (Denis), Vermeire, S. (Séverine), Kubo, M. (Michiaki), Louis, E. (Edouard), Georges, M. (Michel), Abraham, C. (Clara), Achkar, J.-P. (Jean-Paul), Ahmad, T. (Tariq), Ananthakrishnan, A.N. (Ashwin N.), Andersen, V. (Vibeke), Anderson, C.A. (Carl A.), Andrews, J.M. (Jane M.), Annese, V. (Vito), Aumais, G. (Guy), Baidoo, L. (Leonard), Baldassano, R.N. (Robert), Bampton, P.A. (Peter A.), Barclay, M. (Murray), Barrett, J.C. (Jeffrey), Bayless, T.M. (Theodore M.), Bethge, J. (Johannes), Bitton, A., Boucher, G. (Gabrielle), Brand, S. (Stephan), Brandt, B. (Berenice), Brant, S.R. (Steven R.), Büning, C. (Carsten), Chew, A. (Angela), Cho, J.H. (Judy H.), Cleynen, I. (Isabelle), Cohain, A. (Ariella), Croft, A. (Anthony), Daly, M.J. (Mark J.), D'Amato, M. (Mauro), Danese, S. (Silvio), De Jong, D.J. (Dirk J.), Denapiene, G. (Goda), Denson, L.A. (Lee A.), Devaney, K.L. (Kathy L.), Dewit, O. (Olivier), D'Inca, R. (Renata), Dubinsky, M. (Marla), Duerr, R.H. (Richard), Edwards, C. (Cathryn), Ellinghaus, D. (David), Essers, J.B. (Jonah), Ferguson, L.R. (Lynnette R.), Festen, E.A.M. (Eleonora), Fleshner, P. (Philip), Florin, T. (Tim), Franke, A. (Andre), Fransen, K. (Karin), Gearry, R. (Richard), Gieger, C. (Christian), Glas, J. (Jürgen), Goyette, P. (Philippe), Green, T. (Todd), Griffiths, A.M. (Anne), Guthery, S.L. (Stephen L.), Hakonarson, H. (Hakon), Halfvarson, J. (Jonas), Hanigan, K. (Katherine), Haritunians, T. (Talin), Hart, A. (Ailsa), Hawkey, S., Hayward, N.K. (Nicholas K.), Hedl, M. (Matija), Henderson, P. (Paul), Hu, X. (Xinli), Huang, H. (Hailiang), Hui, K.Y. (Ken Y.), Imielinski, M. (Marcin), Ippoliti, A. (Andrew), Jonaitis, L. (Laimas), Jostins, L. (Luke), Karlsen, T.H. (Tom), Kennedy, N.A. (Nicholas A.), Khan, M.A. (Mohammed Azam), Kiudelis, G. (Gediminas), Krishnaprasad, K. (Krupa), Kugathasan, S. (Subra), Kupcinskas, L. (Limas), Latiano, A. (Anna), Laukens, D. (Debby), Lawrance, I.C. (Ian C.), Lee, J.C. (James C.), Lees, C.W. (Charlie), Leja, M. (Marcis), Van Limbergen, J. (Johan), Lionetti, P. (Paolo), Liu, J.Z. (Jimmy Z.), Mahy, G. (Gillian), Mansfield, J. (John), Massey, D. (Dunecan), Mathew, J. (Joseph), McGovern, D.P.B. (Dermot P.B.), Milgrom, R. (Raquel), Mitrovic, M. (Mitja), Montgomery, G.W. (Grant W.), Mowat, C. (Craig), Newman, W.G. (William G.), Ng, A. (Aylwin), Ng, S.C. (Siew C.), Ng, S.M.E. (Sok Meng Evelyn), Nikolaus, S. (Susanna), Ning, K. (Kaida), Nöthen, M.M. (Markus), Oikonomou, I. (Ioannis), Palmieri, O. (Orazio), Parkes, M. (Miles), Phillips, A. (Anne), Ponsioen, C.Y. (Cyril), Potocnik, U. (Uros), Prescott, N.J. (Natalie J.), Proctor, D.D. (Deborah D.), Radford-Smith, G. (Graham), Rahier, J.F. (J.), Raychaudhuri, S. (Soumya), Regueiro, M. (Miguel), Rieder, F. (Florian), Rioux, J.D. (John), Ripke, S. (Stephan), Roberts, R. (Rebecca), Russell, R.K. (Richard), Sanderson, J.D. (Jeremy), Sans, S. (Susana), Satsangi, J. (Jack), Schadt, E.E. (Eric), Schreiber, S. (Stefan), Schulte, D. (Dominik), Schumm, L.P. (L. Philip), Scott, R. (Regan), Seielstad, M. (Mark), Sharma, Y. (Yashoda), Silverberg, M. (Mark), Simms, L.A. (Lisa A.), Skieceviciene, J. (Jurgita), Spain, S.L. (Sarah L.), Steinhart, A.H. (A. Hillary), Stempak, J.M. (Joanne M.), Stronati, L. (Laura), Sventoraityte, J. (Jurgita), Targan, S.R. (Stephan R.), Taylor, K.M. (Kirstin M.), Ter Velde, A. (Anje), Torkvist, L. (Leif), Tremelling, M. (Mark), Van Sommeren, S. (Suzanne), Vasiliauskas, E. (Eric), Verspaget, H.W., Walters, T. (Thomas), Wang, K. (Kai), Wang, M.-H. (Ming-Hsi), Wei, Z. (Zhi), Whiteman, D.C. (David C.), Wijmenga, C. (Cisca), Wilson, D.C. (David C.), Winkelmann, B., Xavier, R.J. (Ramnik J.), Zhang, B. (Bin), Zhang, C.K. (Clarence K.), Zhang, H. (Hu), Zhang, W. (Wei), Zhao, H. (Hongyu), Zhao, Z.Z. (Zhen Z.), Momozawa, Y. (Yukihide), Dmitrieva, J. (Julia), Théâtre, E. (Emilie), Deffontaine, V. (Valérie), Rahmouni, S. (Souad), Charloteaux, B. (Benoît), Crins, F. (François), Docampo, E. (Elisa), Elansary, M. (Mahmoud), Gori, A.-S. (Ann-Stephan), Lecut, C. (Christelle), Mariman, R. (Rob), Mni, M. (Myriam), Oury, C. (Cécile), Altukhov, I. (Ilya), Alexeev, D. (Dmitry), Aulchenko, Y.S. (Yurii), Amininejad, L. (Leila), Bouma, G. (Gerd), Hoentjen, F., Löwenberg, M., Oldenburg, B. (Bas), Pierik, M. (Marieke), Vander Meulen-De Jong, A.E. (Andrea E.), Woude, C.J. (Janneke) van der, Visschedijk, M. (Marijn), Lathrop, M. (Mark), Hugot, J.P. (J.), Weersma, R.K. (Rinse), De Vos, M. (Martine), Franchimont, D. (Denis), Vermeire, S. (Séverine), Kubo, M. (Michiaki), Louis, E. (Edouard), Georges, M. (Michel), Abraham, C. (Clara), Achkar, J.-P. (Jean-Paul), Ahmad, T. (Tariq), Ananthakrishnan, A.N. (Ashwin N.), Andersen, V. (Vibeke), Anderson, C.A. (Carl A.), Andrews, J.M. (Jane M.), Annese, V. (Vito), Aumais, G. (Guy), Baidoo, L. (Leonard), Baldassano, R.N. (Robert), Bampton, P.A. (Peter A.), Barclay, M. (Murray), Barrett, J.C. (Jeffrey), Bayless, T.M. (Theodore M.), Bethge, J. (Johannes), Bitton, A., Boucher, G. (Gabrielle), Brand, S. (Stephan), Brandt, B. (Berenice), Brant, S.R. (Steven R.), Büning, C. (Carsten), Chew, A. (Angela), Cho, J.H. (Judy H.), Cleynen, I. (Isabelle), Cohain, A. (Ariella), Croft, A. (Anthony), Daly, M.J. (Mark J.), D'Amato, M. (Mauro), Danese, S. (Silvio), De Jong, D.J. (Dirk J.), Denapiene, G. (Goda), Denson, L.A. (Lee A.), Devaney, K.L. (Kathy L.), Dewit, O. (Olivier), D'Inca, R. (Renata), Dubinsky, M. (Marla), Duerr, R.H. (Richard), Edwards, C. (Cathryn), Ellinghaus, D. (David), Essers, J.B. (Jonah), Ferguson, L.R. (Lynnette R.), Festen, E.A.M. (Eleonora), Fleshner, P. (Philip), Florin, T. (Tim), Franke, A. (Andre), Fransen, K. (Karin), Gearry, R. (Richard), Gieger, C. (Christian), Glas, J. (Jürgen), Goyette, P. (Philippe), Green, T. (Todd), Griffiths, A.M. (Anne), Guthery, S.L. (Stephen L.), Hakonarson, H. (Hakon), Halfvarson, J. (Jonas), Hanigan, K. (Katherine), Haritunians, T. (Talin), Hart, A. (Ailsa), Hawkey, S., Hayward, N.K. (Nicholas K.), Hedl, M. (Matija), Henderson, P. (Paul), Hu, X. (Xinli), Huang, H. (Hailiang), Hui, K.Y. (Ken Y.), Imielinski, M. (Marcin), Ippoliti, A. (Andrew), Jonaitis, L. (Laimas), Jostins, L. (Luke), Karlsen, T.H. (Tom), Kennedy, N.A. (Nicholas A.), Khan, M.A. (Mohammed Azam), Kiudelis, G. (Gediminas), Krishnaprasad, K. (Krupa), Kugathasan, S. (Subra), Kupcinskas, L. (Limas), Latiano, A. (Anna), Laukens, D. (Debby), Lawrance, I.C. (Ian C.), Lee, J.C. (James C.), Lees, C.W. (Charlie), Leja, M. (Marcis), Van Limbergen, J. (Johan), Lionetti, P. (Paolo), Liu, J.Z. (Jimmy Z.), Mahy, G. (Gillian), Mansfield, J. (John), Massey, D. (Dunecan), Mathew, J. (Joseph), McGovern, D.P.B. (Dermot P.B.), Milgrom, R. (Raquel), Mitrovic, M. (Mitja), Montgomery, G.W. (Grant W.), Mowat, C. (Craig), Newman, W.G. (William G.), Ng, A. (Aylwin), Ng, S.C. (Siew C.), Ng, S.M.E. (Sok Meng Evelyn), Nikolaus, S. (Susanna), Ning, K. (Kaida), Nöthen, M.M. (Markus), Oikonomou, I. (Ioannis), Palmieri, O. (Orazio), Parkes, M. (Miles), Phillips, A. (Anne), Ponsioen, C.Y. (Cyril), Potocnik, U. (Uros), Prescott, N.J. (Natalie J.), Proctor, D.D. (Deborah D.), Radford-Smith, G. (Graham), Rahier, J.F. (J.), Raychaudhuri, S. (Soumya), Regueiro, M. (Miguel), Rieder, F. (Florian), Rioux, J.D. (John), Ripke, S. (Stephan), Roberts, R. (Rebecca), Russell, R.K. (Richard), Sanderson, J.D. (Jeremy), Sans, S. (Susana), Satsangi, J. (Jack), Schadt, E.E. (Eric), Schreiber, S. (Stefan), Schulte, D. (Dominik), Schumm, L.P. (L. Philip), Scott, R. (Regan), Seielstad, M. (Mark), Sharma, Y. (Yashoda), Silverberg, M. (Mark), Simms, L.A. (Lisa A.), Skieceviciene, J. (Jurgita), Spain, S.L. (Sarah L.), Steinhart, A.H. (A. Hillary), Stempak, J.M. (Joanne M.), Stronati, L. (Laura), Sventoraityte, J. (Jurgita), Targan, S.R. (Stephan R.), Taylor, K.M. (Kirstin M.), Ter Velde, A. (Anje), Torkvist, L. (Leif), Tremelling, M. (Mark), Van Sommeren, S. (Suzanne), Vasiliauskas, E. (Eric), Verspaget, H.W., Walters, T. (Thomas), Wang, K. (Kai), Wang, M.-H. (Ming-Hsi), Wei, Z. (Zhi), Whiteman, D.C. (David C.), Wijmenga, C. (Cisca), Wilson, D.C. (David C.), Winkelmann, B., Xavier, R.J. (Ramnik J.), Zhang, B. (Bin), Zhang, C.K. (Clarence K.), Zhang, H. (Hu), Zhang, W. (Wei), Zhao, H. (Hongyu), and Zhao, Z.Z. (Zhen Z.)

Abstract

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.

Published
2018
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7. Neoprene Orthopaedic Supports: An Underrecognised Cause of Allergic Contact Dermatitis

Author

Hawkey, S. and Ghaffar, S.

Subjects
Article Subject
Abstract

Thioureas, often contained within neoprene to provide water resistance, are an important cause of allergic contact dermatitis (ACD) in those who use neoprene products. We wish to present three cases of thiourea-induced ACD from three different orthopaedic supports containing neoprene. The first case was a 67-year-old woman who developed an itchy rash on her heel three weeks after using a neoprene insole for plantar fasciitis. The second case was a 47-year-old man who developed an itchy rash on his wrist after wearing neoprene wrist splints for psoriatic arthropathy. The third case was a 77-year-old woman who experienced a severe erythematous rash with blistering from a neoprene elbow brace she received following a humeral fracture. All patients were patch tested to the British Society of Cutaneous Allergy Standard and rubber series and a cut piece from all the relevant supports. At 96 hours, all patients had a + reaction to mixed dialkylthiourea, diethylthiourea, and the supports’ material. No other positive patch test reactions were identified. As neoprene is fast becoming one of the most popular materials used for orthopaedic supports, awareness of this reaction and close liaison between dermatologists and orthopaedic surgeons are therefore essential to allow for early recognition of this complication.

Published
2015
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8. Serratia marcescens: A Rare Cause of Recurrent Implantable Cardioverter Defibrillator Site Infection

Author

Hawkey, S. and Choy, AM.

Subjects
Article Subject
Abstract

We present a unique case of a patient who experienced recurrent infections of his implantable cardioverter defibrillator (ICD) site with the bacterium Serratia marcescens. This report highlights the virulence of this bacterium, its resistance to antibiotic therapy, and its ability to remain latent for prolonged periods between episodes of sepsis. It also demonstrates the merits of reimplanting devices at different sites in the context of Serratia marcescens infection.

Published
2015
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9. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

Author

Kaman, W.E. (Wendy), Hawkey, S., Kleij, D. (Desiree) van der, Broekhuijsen, M.P., Silman, N.J., Bikker, F.J. (Floris), Kaman, W.E. (Wendy), Hawkey, S., Kleij, D. (Desiree) van der, Broekhuijsen, M.P., Silman, N.J., and Bikker, F.J. (Floris)

Abstract

We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF-strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression.

Published
2011
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10. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

Author

Kaman, Wendy, Hawkey, S, Van der Kleij, D, Broekhuijsen, MP, Silman, NJ, Bikker, FJ, Kaman, Wendy, Hawkey, S, Van der Kleij, D, Broekhuijsen, MP, Silman, NJ, and Bikker, FJ

Abstract

We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF(-) strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression.

Published
2011

15. Oral prednisolone for acute lower respiratory tract infection in clinically unrecognised asthma: an exploratory analysis of the Oral Steroids for Acute Cough (OSAC) randomised controlled trial.

Author

Hawkey S, Young GJ, Little P, Moore M, and Hay AD

Abstract

Background: Acute lower respiratory tract infection (ALRTI) is often treated in primary care with antibiotics. The recent Oral Steroids for Acute Cough (OSAC) randomised controlled trial (RCT) showed corticosteroids were not an effective alternative in adults without a diagnosis of asthma with ALRTI., Aim: To investigate if corticosteroids are beneficial for ALRTI in patients with unrecognised asthma., Design & Setting: An exploratory analysis was undertaken of the primary care OSAC trial., Method: A subgroup analysis was performed in patients who responded 'yes' to the following International Primary Care Airways Group (IPCAG) question: did you have wheeze and/or at least two of nocturnal cough or chest tightness or dyspnoea in the past year. Sensitivity analyses were carried out on those who answered 'yes' to wheeze and at least two of the nocturnal symptoms. The primary outcomes were as follows: duration of cough (0-28 days, minimum clinically important difference [MCID] of 3.79 days) and mean symptom severity score (range 0-6; MCID 1.66 units)., Results: In total, 40 (10%) patients were included in the main analysis: mean age 49 years (standard deviation [SD] = 17.9), 52% male. Median cough duration was 3 days in both prednisolone (interquartile range [IQR] = 2-6 days) and placebo (IQR = 1-6 days) groups (adjusted hazard ratio [HR] = 1.10; 95% confidence interval [CI] = 0.47 to 2.54; P = 0.83), equating to 0.24 days longer in the prednisolone group (95% CI = 1.23 days shorter to 2.88 days longer). Mean symptom severity difference was -0.14 (95% CI = -0.78 to 0.49; P =0.65) comparing prednisolone with placebo. Similar findings were found in the sensitivity analysis., Conclusion: No evidence was found to support the use of corticosteroids for ALRTI in patients with clinically unrecognised asthma. Clinicians should not use the IPCAG questions to target oral corticosteroid treatment in patients with ALRTI., (Copyright © 2020, The Authors.)

Published
2020
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16. Association between guidelines and medical practitioners' perception of best management for patients attending with an apparently uncomplicated acute sore throat: a cross-sectional survey in five countries.

Author

Gunnarsson R, Ebell MH, Wächtler H, Manchal N, Reid L, Malmberg S, Hawkey S, Hay AD, Hedin K, and Sundvall PD

Subjects
Adult, Anti-Bacterial Agents therapeutic use, Australia, Child, Cross-Sectional Studies, Germany, Humans, Perception, Sweden, Pharyngitis diagnosis, Pharyngitis drug therapy
Abstract

Objective: To investigate the relationship between guidelines and the medical practitioners' perception of optimal care for patients attending with an apparently uncomplicated acute sore throat in five countries (Australia, Germany, Sweden, UK and USA)., Design: International cross-sectional survey., Setting: Primary healthcare (PHC)., Participants: Medical practitioners working in PHC., Main Outcome Measures: ORs for: (A) perception of throat swabs as important, (B) perception of blood tests (C reactive protein, B-ESR and B-leucocytes) as important and (C) antibiotic prescriptions if no pathogenic bacteria isolated on throat swab., Results: Guidelines differed significantly; those recommending throat swabs (Sweden and USA) were associated with practitioners perceiving them as important. The UK guideline was the only one actively discouraging the use of throat swabs. Hence, compared with the USA (reference), a throat swab showing no pathogenic bacteria increased the probability of antibiotic prescribing in the UK with OR 3.2 (95% CI 1.7 to 6.1) for adults, whereas it reduced the probability in Sweden for adults OR 0.35 (95% CI 0.13 to 0.96) and children 0.19 (95% CI 0.069 to 0.50)., Conclusions: The differences between practitioners' perceptions of best management were associated with their guidelines. It remains unclear if guidelines influenced medical practitioners' perception or if guidelines merely reflect the consensus of current practice. A larger effort should be made to reach an international consensus in high-income countries about the best management of patients attending for an uncomplicated acute sore throat., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2020
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17. The Use of Germinants to Potentiate the Sensitivity of Bacillus anthracis Spores to Peracetic Acid.

Author

Celebi O, Buyuk F, Pottage T, Crook A, Hawkey S, Cooper C, Bennett A, Sahin M, and Baillie L

Abstract

Elimination of Bacillus anthracis spores from the environment is a difficult and costly process due in part to the toxicity of current sporicidal agents. For this reason we investigated the ability of the spore germinants L-alanine (100 mM) and inosine (5 mM) to reduce the concentration of peracetic acid (PAA) required to inactivate B. anthracis spores. While L-alanine significantly enhanced (p = 0.0085) the bactericidal activity of 500 ppm PAA the same was not true for inosine suggesting some form of negative interaction. In contrast the germinant combination proved most effective at 100 ppm PAA (p = 0.0009). To determine if we could achieve similar results in soil we treated soil collected from the burial site of an anthrax infected animal which had been supplemented with spores of the Sterne strain of B. anthracis to increase the level of contamination to 10(4) spores/g. Treatment with germinants followed 1 h later by 5000 ppm PAA eliminated all of the spores. In contrast direct treatment of the animal burial site using this approach delivered using a back pack sprayer had no detectable effect on the level of B. anthracis contamination or on total culturable bacterial numbers over the course of the experiment. It did trigger a significant, but temporary, reduction (p < 0.0001) in the total spore count suggesting that germination had been triggered under real world conditions. In conclusion, we have shown that the application of germinants increase the sensitivity of bacterial spores to PAA. While the results of the single field trial were inconclusive, the study highlighted the potential of this approach and the challenges faced when attempting to perform real world studies on B. anthracis spores contaminated sites.

Published
2016
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18. Underutilization of IV nitrates in the treatment of acute heart failure.

Author

Mohan M, Hawkey S, Baig F, Choy AM, and Lang CC

Subjects
Acute Disease, Administration, Intravenous, Aged, Aged, 80 and over, Comorbidity, Drug Utilization Review, Female, Guideline Adherence trends, Heart Failure diagnosis, Heart Failure epidemiology, Heart Failure physiopathology, Hospitals, Teaching, Humans, Male, Nitrates adverse effects, Patient Admission, Practice Guidelines as Topic, Prospective Studies, Retrospective Studies, Risk Factors, Scotland epidemiology, Sodium Potassium Chloride Symporter Inhibitors administration & dosage, Time Factors, Treatment Outcome, Vasodilator Agents adverse effects, Heart Failure drug therapy, Nitrates administration & dosage, Practice Patterns, Physicians' trends, Vasodilator Agents administration & dosage
Abstract

Acute heart failure (AHF) is a growing public health concern with high inhospital mortality and costs. Clinical practice guidelines, underpinned by positive randomized controlled trials, recommend the early use of intravenous (IV) nitrates in the treatment of AHF. However, the "real-world" usage of IV nitrates has not been clearly defined. The objective of this study was to examine the use of IV nitrates in the treatment of AHF as recommended by clinical practice guidelines. A case-record analysis was conducted of all admissions with AHF at a large teaching hospital. Of the 81 AHF patients (mean age 77 ± 11, mean SBP 130 ± 27 mmHg) enrolled for this analysis, only 5 (6%) received IV nitrates at the time of AHF admission. Forty (49%, mean age 77 ± 11, mean SBP 131 ± 27 mmHg) of these 81 patients met the guideline criteria for suitability for IV nitrates and only 5 (12%) of these received them during this admission. Patients who received IV nitrates were more likely to have higher blood pressure and all had myocardial ischemia as a precipitant. Seventy-five (93%) of the total population received loop diuretics on admission. Overall, this study shows that loop diuretics remain the first-line therapy in AHF with little use of IV nitrates, despite recommendations from clinical practice guidelines., (© 2015 John Wiley & Sons Ltd.)

Published
2015
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19. An algorithm for setting priorities and selecting target wastes for minimization.

Author

Hawkey SA

Subjects
Hazardous Waste economics, Hazardous Waste prevention & control, United States, Algorithms, Hazardous Waste classification
Abstract

Implementation of waste minimization programs has been routinely assigned to industrial hygienists. The first question that needs to be answered in program development is, "Which waste is the worst offender?" To answer this, all potential variables that define and describe the wastes must be analyzed and a conclusion drawn. An algorithm has been successfully developed and used to set priorities for minimization activities. This algorithm is used to prepare a matrix that gives priority to the different wastes generated and identifies the logical first target for minimization. The variables analyzed include the weight of the waste generated, total cost for disposal of that waste, long-term and short-term liability resulting from management of the waste, quantity of releases to the environment, cost of replacement raw materials, and toxicity and characteristics of the waste. Each of these variables is defined to be compatible with regulatory definitions. Factors for each variable are assigned and plugged into the algorithm's equation. The operations of the equation have been developed to provide different weights to the factors. From this calculation, the first priority for waste minimization can be chosen.

Published
1992
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