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2. Integrating a newly developed BAC-based physical mapping resource for Lolium perenne with a genome-wide association study across a L. perenne European ecotype collection identifies genomic contexts associated with agriculturally important traits

Author

Harper, J., De Vega, J., Swain, S., Heavens, D., Gasior, D., Thomas, A., Evans, C., Lovatt, A., Lister, S., Thorogood, D., Skøt, L., Hegarty, M., Blackmore, T., Kudrna, D., Byrne, S., Asp, T., Powell, W., Fernandez-Fuentes, N., and Armstead, I.

Published
2019

7. The role of impaired synaptic plasticity in aberrant salience

Author

Blackmore, T, Bannerman, D, and Walton, M

Abstract

Hippocampal network dysfunction has been recognised as a potential pathway to psychotic symptoms for many years. Reduced hippocampal synaptic plasticity is a core feature in a diverse range of conditions, from Alzheimer’s Disease to depression and schizophrenia, and may explain overlap in symptom domains across these disorders. This thesis has investigated cognitive impairments in mouse models relevant to schizophrenia, in the context of their known effects on synaptic plasticity; integrating these effects into a psychological framework for associative learning and attention. Hippocampal long-term potentiation requires finely balanced tuning of glutamatergic signalling via expression of NMDA and AMPA receptors at the synapse. We manipulated this balance by genetic knockout of the AMPA receptor subunit GluA1, or through pharmacological blockade of the NMDA receptor with MK-801. Additionally, we investigated the effect of increased dopamine transmission, also heavily implicated in schizophrenia, by acute administration of amphetamine. Through extensive motor and cognitive profiling, we revealed divergent behavioural phenotypes dependent on the circuit manipulation. Glutamatergic dysfunction induced significant locomotor hyperactivity and impaired short-term habituation, but when investigated in more detail we saw increased responding specifically to repeatedly presented stimuli; indicative of stimulus-specific sensitisation. While amphetamine also induced hyperactivity, this was stimulus-independent and appeared to reflect general increases in arousal and attention regardless of environment. We then went on to investigate how these deficits in habituation affect attentional processing in the 5-choice serial reaction time test. All treatment groups showed unique behavioural abnormalities in tests of attention. The increased arousal following amphetamine treatment was observed here again, to the point that animals were impaired in their ability to respond appropriately. MK-801 seemingly induced global deficits in attention that impaired an animals’ ability to attend to the task, whereas GluA1 knockout left attending largely intact until conditions were made unpredictable. Finally we investigated how impaired short-term habituation and attentional processes in GluA1-/- mice affect their ability to accurately form associations using sensory preconditioning. Mice lacking GluA1 showed enhanced performance in this task under simple conditions, indicating an increased propensity to form associations. When conditions were more complex, however, they were impaired. These data suggest maladaptive associative learning in GluA1-/- that can be beneficial or harmful to learning, depending on the circumstances. These findings show that perturbations of glutamate transmission affect an individual’s ability to accurately learn about their environment and suggest a mechanism through which this actually leads to sensitisation to recently familiar stimuli as a result of deficits in short-term habituation. The impact of this impairment on associative learning indicates a critical role for hippocampal long-term potentiation in this mechanism, and also suggests that GluA1-/- share construct validity with clinical psychosis.

Published
2022

9. Patient-reported diagnostic intervals to colorectal cancer diagnosis in the Midland region of New Zealand: a prospective cohort study

Author

Blackmore, T, Chepulis, L, Rawiri, K, Kidd, J, Stokes, T, Firth, M, Elwood, M, Weller, D, Emery, J, Lawrenson, R, Blackmore, T, Chepulis, L, Rawiri, K, Kidd, J, Stokes, T, Firth, M, Elwood, M, Weller, D, Emery, J, and Lawrenson, R

Abstract

BACKGROUND AND OBJECTIVES: New Zealand (NZ) has high rates of colorectal cancer (CRC) but low rates of early detection. The majority of CRC is diagnosed through general practice, where lengthy diagnostic intervals are common. We investigated factors contributing to diagnostic delay in a cohort of patients newly diagnosed with CRC. METHODS: Patients were recruited from the Midland region and interviewed about their diagnostic experience using a questionnaire based on a modified Model of Pathways to Treatment framework and SYMPTOM questionnaire. Descriptive statistics were used to describe the population characteristics. Chi-square analysis and logistic regression were used to analyse factors influencing diagnostic intervals. RESULTS: Data from 176 patients were analysed, of which 65 (36.9%) experienced a general practitioner (GP) diagnostic interval of >120 days and 96 (54.5%) experienced a total diagnostic interval (TDI) > 120 days. Patients reporting rectal bleeding were less likely to experience a long TDI (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.14-0.78) and appraisal/help-seeking interval (OR, 0.19, 95% CI: 0.06-0.59). Patients <60 were more likely to report a longer appraisal/help-seeking interval (OR, 3.32, 95% CI: 1.17-9.46). Female (OR, 2.19, 95% CI: 1.08-4.44) and Māori patients (OR, 3.18, 95% CI: 1.04-9.78) were more likely to experience a long GP diagnostic interval. CONCLUSION: NZ patients with CRC can experience long diagnostic intervals, attributed to patient and health system factors. Young patients, Māori, females, and patients experiencing change of bowel habit may be at particular risk. We need to increase symptom awareness of CRC for patients and GPs. Concentrated efforts are needed to ensure equity for Māori in access to screening, diagnostics, and treatment.

Published
2022

14. Why does New Zealand have such poor outcomes from colorectal cancer?: the importance of the pre-diagnostic period

Author

Firth, M, Blackmore, T, Chepulis, L, Keenan, R, Stokes, T, Elwood, M, Weller, D, Emery, J, Lawrenson, R, Firth, M, Blackmore, T, Chepulis, L, Keenan, R, Stokes, T, Elwood, M, Weller, D, Emery, J, and Lawrenson, R

Abstract

INTRODUCTION Over 3000 cases of colorectal cancer (CRC) are diagnosed annually in New Zealand. The proportion of late stage diagnoses is higher than in similar countries, and highest in Māori and Pacific patients. Survival outcomes are poorer than for people in Australia and poor for Māori and Pacific peoples. A regional screening programme is not yet available to the entire target population (60-74 years). AIM This study reviews research investigating the pre-diagnostic pathway for CRC in New Zealand and how this may contribute to poorer outcomes. METHODS This was a scoping review of original articles examining the pre-diagnostic period for CRC published on the PubMed database between 2009 and 2019. Findings were interpreted within the Model of Pathways to Treatment framework and in context of international evidence. RESULTS In total, 83 publications were assessed; eight studies were included. Studies were mainly older than 5 years, qualitative, and focused on screening. Facilitatory factors for the appraisal and help-seeking intervals increased CRC public awareness and the critical role of general practitioners. No specific facilitatory or inhibitory factors were identified for the diagnostic interval, but two studies found that time frames did not meet national and international targets. One study discovered longer pre-diagnostic intervals were associated with younger age at diagnosis. DISCUSSION Limited recent research has investigated the CRC pre-diagnostic pathways in NZ. Identification of facilitatory and inhibitory factors and implementation of appropriate strategies to improve them alongside the wider uptake of the screening programme may improve stage at diagnosis and outcomes for New Zealand CRC patients.

Published
2021

15. Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis

Author

Lawrenson, R, Moosa, S, Warren, J, van Dalen, R, Chepulis, L, Blackmore, T, Lao, C, Mayo, C, Kidd, J, Firth, M, Stokes, T, Elwood, M, Weller, D, Emery, J, Lawrenson, R, Moosa, S, Warren, J, van Dalen, R, Chepulis, L, Blackmore, T, Lao, C, Mayo, C, Kidd, J, Firth, M, Stokes, T, Elwood, M, Weller, D, and Emery, J

Abstract

BACKGROUND: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. METHODS: This study is a retrospective analysis of e-referral data for patients aged 30-70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015-31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. RESULTS: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Māori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Māori having a colonoscopy was 0.66 (95% CI 0.60-0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35-2.07) for men compared to women, and 2.34 (95% CI 1.70-3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. CONCLUSIONS: If a GP refers a patient with an HSCan, and the patien

Published
2021

16. How do colorectal cancer patients rate their GP: a mixed methods study

Author

Blackmore, T, Chepulis, L, Keenan, R, Kidd, J, Stokes, T, Weller, D, Emery, J, Lawrenson, R, Blackmore, T, Chepulis, L, Keenan, R, Kidd, J, Stokes, T, Weller, D, Emery, J, and Lawrenson, R

Abstract

BACKGROUND: New Zealand (NZ) has a high incidence of colorectal cancer (CRC) and low rates of early diagnosis. With screening not yet nationwide, the majority of CRC is diagnosed through general practice. A good patient-general practitioner (GP) relationship can facilitate prompt diagnosis, but when there is a breakdown in this relationship, delays can occur. Delayed diagnosis of CRC in NZ receives a disproportionally high number of complaints directed against GPs, suggesting deficits in the patient-GP connection. We aimed to investigate patient-reported confidence and ratings of their GP following the diagnostic process. METHODS: This study is a mixed methods analysis of responses to a structured questionnaire and free text comments from patients newly diagnosed with CRC in the Midland region of NZ. A total of 195 patients responded to the structured questionnaire, and 113 patients provided additional free text comments. Descriptive statistics were used to describe the study population and chi square analysis determined the statistical significance of factors possibly linked to delay. Free text comments were analysed using a thematic framework. RESULTS: Most participants rated their GP as 'Very good/Good' at communication with patients about their health conditions and involving them in decisions about their care, and 6.7% of participants rated their overall level of confidence and trust in their GP as 'Not at all'. Age, gender, ethnicity and a longer diagnostic interval were associated with lower confidence and trust. Free text comments were grouped in to three themes: 1. GP Interpersonal skills; (communication, listening, taking patient symptoms seriously), 2. Technical competence; (speed of referral, misdiagnoses, lack of physical examination), and 3. Organisation of general practice care; (appointment length, getting an appointment, continuity of care). CONCLUSIONS: Māori, females, and younger participants were more likely to report low confidence and trust in

Published
2021

23. Barriers and facilitators to colorectal cancer diagnosis in New Zealand: a qualitative study

Author

Blackmore, T, Norman, K, Kidd, J, Cassim, S, Chepulis, L, Keenan, R, Firth, M, Jackson, C, Stokes, T, Weller, D, Emery, J, Lawrenson, R, Blackmore, T, Norman, K, Kidd, J, Cassim, S, Chepulis, L, Keenan, R, Firth, M, Jackson, C, Stokes, T, Weller, D, Emery, J, and Lawrenson, R

Abstract

BACKGROUND: New Zealand (NZ) has high rates of colorectal cancer but low rates of early diagnosis. Due to a lack of understanding of the pre-diagnostic experience from the patient's perspective, it is necessary to investigate potential patient and health system factors that contribute to longer diagnostic intervals. Previous qualitative studies have discussed delays using The Model of Pathways to Treatment, but this has not been explored in the NZ context. This study aimed to understand the patient experience and perception of their general practitioner (GP) through the diagnostic process in the Waikato region of NZ. In particular, we sought to investigate potential barriers and facilitators that contribute to longer diagnostic intervals. METHODS: Ethical approval for this study was granted by the New Zealand Health and Disability Ethics Committee. Twenty-eight participants, diagnosed with colorectal cancer, were interviewed about their experience. Semi-structured interviews were audio recorded, transcribed verbatim and analysed thematically using The Model of Pathways to Treatment framework (intervals: appraisal, help-seeking, diagnostic). RESULTS: Participant appraisal of symptoms was a barrier to prompt diagnosis, particularly if symptoms were normalised, intermittent, or isolated in occurrence. Successful self-management techniques also resulted in delayed help-seeking. However if symptoms worsened, disruption to work and daily routines were important facilitators to seeking a GP consultation. Participants positively appraised GPs if they showed good technical competence and were proactive in investigating symptoms. Negative GP appraisals were associated with a lack of physical examinations and misdiagnosis, and left participants feeling dehumanised during the diagnostic process. However high levels of GP interpersonal competence could override poor technical competence, resulting in an overall positive experience, even if the cancer was diagnosed at an advanced

Published
2020

28. Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study

Author

Murray, D. D., Suzuki, K., Law, M., Trebicka, J., Neuhaus, J., Wentworth, D., Johnson, M., Vjecha, M. J., Kelleher, A. D., Emery, S., Aagaard, B., Aragon, E., Arnaiz, J., Borup, L., Clotet, B., Dragsted, U., Fau, A., Gey, D., Grarup, J., Hengge, U., Herrero, P., Jansson, P., Jensen, B., Jensen, K., Juncher, H., Lopez, P., Lundgren, J. D., Matthews, C., Mollerup, D., Pearson, M., Phillips, A., Reilev, S., Tillmann, K., Varea, S., Angus, B., Babiker, A., Cordwell, B., Darbyshire, J., Dodds, W., Fleck, S., Horton, J., Hudson, F., Moraes, Y., Pacciarini, F., Palfreeman, A., Paton, N., Smith, N., Van Hooff, F., Bebchuk, J., Collins, G., Denning, E., Duchene, A., Fosdick, L., Harrison, M., Herman-Lamin, K., Krum, E., Larson, G., Neaton, J., Nelson, R., Quan, K., Quan, S., Schultz, T., Thompson, G., Wyman, N., Carey, C., Chan, F., Cooper, D., Courtney-Rodgers, D., Drummond, F., Harrod, M., Jacoby, S., Kearney, L., Lin, E., Pett, S., Robson, R., Seneviratne, N., Stewart, M., Watts, E., Finley, E., Gordin, F., Sanchez, A., Standridge, B., Belloso, W., Davey, R., Duprez, D., Gatell, J., Hoy, J., Lifson, A., Pederson, C., Perez, G., Price, R., Prineas, R., Rhame, F., Sampson, J., Worley, J., Modlin, J., Beral, V., Chaisson, R., Fleming, T., Hill, C., Kim, K., Murray, B., Pick, B., Seligmann, M., Weller, I., Cahill, K., Fox, L., Luzar, M., Martinez, A., Mcnay, L., Pierson, J., Tierney, J., Vogel, S., Costas, V., Eckstrand, J., Brown, S., Abusamra, L., Angel, E., Aquilia, S., Benetucci, J., Bittar, V., Bogdanowicz, E., Cahn, P., Casiro, A., Contarelli, J., Corral, J., Daciuk, L., David, D., Dobrzanski, W., Duran, A., Ebenrstejin, J., Ferrari, I., Fridman, D., Galache, V., Guaragna, G., Ivalo, S., Krolewiecki, A., Lanusse, I., Laplume, H., Lasala, M., Lattes, R., Lazovski, J., Lopardo, G., Losso, M., Lourtau, L., Lupo, S., Maranzana, A., Marson, C., Massera, L., Moscatello, G., Olivia, S., Otegui, I., Palacios, L., Parlante, A., Salomon, H., Sanchez, M., Somenzini, C., Suarez, C., Tocci, M., Toibaro, J., Zala, C., Agrawal, S., Ambrose, P., Anderson, C., Anderson, J., Baker, D., Beileiter, K., Blavius, K., Bloch, M., Boyle, M., Bradford, D., Britton, P., Brown, P., Busic, T., Cain, A., Carrall, L., Carson, S., Chenoweth, I., Chuah, J., Clark, F., Clemons, J., Clezy, K., Cortissos, P., Cunningham, N., Curry, M., Daly, L., D'Arcy-Evans, C., Del Rosario, R., Dinning, S., Dobson, P., Donohue, W., Doong, N., Downs, C., Edwards, E., Edwards, S., Egan, C., Ferguson, W., Finlayson, R., Forsdyke, C., Foy, L., Franic, T., Frater, A., French, M., Gleeson, D., Gold, J., Habel, P., Haig, K., Hardy, S., Holland, R., Hudson, J., Hutchison, R., Hyland, N., James, R., Johnston, C., Kelly, M., King, M., Kunkel, K., Lau, H., Leamy, J., Lester, D., Leung, J., Lohmeyer, A., Lowe, K., Macrae, K., Magness, C., Martinez, O., Maruszak, H., Medland, N., Miller, S., Murray, J., Negus, P., Newman, R., Ngieng, M., Nowlan, C., Oddy, J., Orford, N., Orth, D., Patching, J., Plummer, M., Price, S., Primrose, R., Prone, I., Ree, H., Remington, C., Richardson, R., Robinson, S., Rogers, G., Roney, J., Roth, N., Russell, D., Ryan, S., Sarangapany, J., Schmidt, T., Schneider, K., Shields, C., Silberberg, C., Shaw, D., Skett, J., Smith, D., Soo, T. M., Sowden, D., Street, A., Tee, B. K., Thomson, J., Topaz, S., Vale, R., Villella, C., Walker, A., Watson, A., Wendt, N., Williams, L., Youds, D., Aichelburg, A., Cichon, P., Gemeinhart, B., Rieger, A., Schmied, B., Touzeau-Romer, V., Vetter, N., Colebunders, R., Clumeck, N., Deroo, A., Kabeya, K., O'Doherty, E., De Wit, S., De Salles Amorim, C., Basso, C., Flint, S., Kallas, E., Levi, G., Lewi, D., Pereira, L., Da Silva, M., Souza, T., Toscano, A., Angel, J., Arsenault, M., Bast, M., Beckthold, B., Bouchard, P., Chabot, I., Clarke, R., Cohen, J., Cote, P., Ellis, M., Gagne, C., Gill, J., Houde, M., Johnston, B., Jubinville, N., Kato, C., Lamoureux, N., Latendre-Paquette, J., Lindemulder, A., Mcneil, A., Mcfarland, N., Montaner, J., Morrisseau, C., O'Neill, R., Page, G., Piche, A., Pongracz, B., Preziosi, H., Puri, L., Rachlis, A., Ralph, E., Raymond, I., Rouleau, D., Routy, J. P., Sandre, R., Seddon, T., Shafran, S., Sikora, C., Smaill, F., Stromberg, D., Trottier, S., Walmsley, S., Weiss, K., Williams, K., Zarowny, D., Baadegaard, B., Andersen, A. B., Boedker, K., Collins, P., Gerstoft, J., Jensen, L., Moller, H., Andersen, P. L., Loftheim, I., Mathiesen, L., Nielsen, H., Obel, N., Pedersen, C., Petersen, D., Jensen, L. P., Black, F. T., Aboulker, J. P., Aouba, A., Bensalem, M., Berthe, H., Blanc, C., Bornarel, D., Bouchaud, O., Boue, F., Bouvet, E., Brancon, C., Breaud, S., Brosseau, D., Brunet, A., Capitant, C., Ceppi, C., Chakvetadze, C., Cheneau, C., Chennebault, J. M., De Truchis, P., Delavalle, A. M., Delfraissy, J. F., Dellamonica, P., Dumont, C., Edeb, N., Fabre, G., Ferrando, S., Foltzer, A., Foubert, V., Gastaut, J. A., Gerbe, J., Girard, P. M., Goujard, C., Hoen, B., Honore, P., Hue, H., Hynh, T., Jung, C., Kahi, S., Katlama, C., Lang, J. M., Le Baut, V., Lefebvre, B., Leturque, N., Levy, Y., Loison, J., Maddi, G., Maignan, A., Majerholc, C., De Boever, C., Meynard, J. L., Michelet, C., Michon, C., Mole, M., Netzer, E., Pialoux, G., Poizot-Martin, I., Raffi, F., Ratajczak, M., Ravaux, I., Reynes, J., Salmon-Ceron, D., Sebire, M., Simon, A., Tegna, L., Tisne-Dessus, D., Tramoni, C., Viard, J. P., Vidal, M., Viet-Peaucelle, C., Weiss, L., Zeng, A., Zucman, D., Adam, A., Arasteh, K., Behrens, G., Bergmann, F., Bickel, M., Bittner, D., Bogner, J., Brockmeyer, N., Darrelmann, N., Deja, M., Doerler, M., Esser, S., Faetkenheuer, G., Fenske, S., Gajetzki, S., Goebel, F., Gorriahn, D., Harrer, E., Harrer, T., Hartl, H., Hartmann, M., Heesch, S., Jakob, W., Jager, H., Klinker, H., Kremer, G., Ludwig, C., Mantzsch, K., Mauss, S., Meurer, A., Niedermeier, A., Pittack, N., Plettenberg, A., Potthoff, A., Probst, M., Rittweger, M., Rockstroh, J., Ross, B., Rotty, J., Rund, E., Ruzicka, T., Schmidt, R., Schmutz, G., Schnaitmann, E., Schuster, D., Sehr, T., Spaeth, B., Staszewski, S., Stellbrink, H. J., Stephan, C., Stockey, T., Stoehr, A., Trein, A., Vaeth, T., Vogel, M., Wasmuth, J., Wengenroth, C., Winzer, R., Wolf, E., Mulcahy, F., Reidy, D., Cohen, Y., Drora, G., Eliezer, I., Godo, O., Kedem, E., Magen, E., Mamorsky, M., Pollack, S., Sthoeger, Z., Vered, H., Yust, I., Aiuti, F., Bechi, M., Bergamasco, A., Bertelli, D., Bruno, R., Butini, L., Cagliuso, M., Carosi, G., Casari, S., Chrysoula, V., Cologni, G., Conti, V., Costantini, A., Corpolongo, A., D'Offizi, G., Gaiottino, F., Di Pietro, M., Esposito, R., Filice, G., Francesco, M., Gianelli, E., Graziella, C., Magenta, L., Martellotta, F., Maserati, R., Mazzotta, F., Murdaca, G., Nardini, G., Nozza, S., Puppo, F., Pogliaghi, M., Ripamonti, D., Ronchetti, C., Rusconi, S., Rusconi, V., Sacchi, P., Silvia, N., Suter, F., Tambussi, G., Uglietti, A., Vechi, M., Vergani, B., Vichi, F., Vitiello, P., Iwamoto, A., Kikuchi, Y., Miyazaki, N., Mori, M., Nakamura, T., Odawara, T., Oka, S., Shirasaka, T., Tabata, M., Takano, M., Ueta, C., Watanabe, D., Yamamoto, Y., Erradey, I., Himmich, H., El Filali, K. M., Blok, W., Van Boxtel, R., Doevelaar, K. B. H., Van Eeden, A., Grijsen, M., Groot, M., Juttmann, J., Kuipers, M., Ligthart, S., Van Der Meulen, P., Lange, J., Langebeek, N., Reiss, P., Richter, C., Schoemaker, M., Schrijnders-Gudde, L., Septer-Bijleveld, E., Sprenger, H., Vermeulen, J., Ten Kate, R., Van De Ven, B., Bruun, J., Kvale, D., Maeland, A., Bakowska, E., Beniowski, M., Boron-Kaczmarska, A., Gasiorowski, J., Horban, A., Inglot, M., Knysz, B., Mularska, E., Parczewski, M., Pynka, M., Rymer, W., Szymczak, A., Aldir, M., Antunes, F., Baptista, C., Da Conceicao Vera, J., Doroana, M., Mansinho, K., Dos Santos, C. R. A., Valadas, E., Vaz Pinto, I., Chia, E., Foo, E., Karim, F., Lim, P. L., Panchalingam, A., Quek, A., Alcazar-Caballero, R., Arribas, J., Arrizabalaga, J., De Barron, X., Blanco, F., Bouza, E., Bravo, I., Calvo, S., Carbonero, L., Carpena, I., Castro, M., Cortes, L., Del Toro, M., Domingo, P., Elias, M., Espinosa, J., Estrada, V., Fernandez-Cruz, E., Fernandez, P., Freud, H., Fuster, M., Garcia, A., Garcia, G., Garrido, R., Gijon, P., Gonzalez-Garcia, J., Gil, I., Gonzalez, A., Gonzalez-Lahoz, J., Grosso, P. 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M., Peters, S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, G., Youle, M., Abrams, D. I., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Crane, L. R., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, A., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. 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K., Visnegarwala, F., Wade, H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Pacheco, Antonio Guilherme

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, General Science & Technology, Anti-HIV Agents, T cell, lcsh:Medicine, Antiretroviral Therapy, HIV Infections, Biology, Essential hypertension, Logistic regression, Malignancy, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Antiretroviral Therapy, Highly Active, microRNA, medicine, Genetics, 2.1 Biological and endogenous factors, Humans, Highly Active, Aetiology, lcsh:Science, Genetic Association Studies, Multidisciplinary, lcsh:R, Case-control study, Middle Aged, medicine.disease, 3. Good health, Circulating MicroRNA, MicroRNAs, medicine.anatomical_structure, Infectious Diseases, Good Health and Well Being, INSIGHT ESPRIT and SMART Study Groups, Immunology, HIV-1, HIV/AIDS, lcsh:Q, Female, Infection, Biomarkers, Biotechnology, Research Article
Abstract

Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Published
2015

29. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study

Author

Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, Lundgren, J. D., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Kirk, O., Reiss, P., Weber, R., Pradier, C., Law, M., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Ryom, L., Kamara, D., Smith, C., Mocroft, A., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbøl Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundström, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjær, J., Sjøl, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Ross, M., Fux, C. A., Morlat, P., Moranne, O., Kesselring, A. M., Kamara, D. A., Friis-Møller, N., Kowalska, J., Sabin, C., Bruyand, M., Bower, M., Fätkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven, C. J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. 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W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. 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J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., University College of London [London] (UCL), University of Copenhagen = Københavns Universitet (KU), University of New South Wales [Sydney] (UNSW), University of Amsterdam [Amsterdam] (UvA), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Interne Geneeskunde, Chemical Biology, Mocroft, A, Lundgren, J, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, C, Moranne, O, Morlat, P, Johnson, M, Ryom, L, Gori, A, Internal medicine, CCA - Innovative therapy, ICaR - Circulation and metabolism, Medical Microbiology and Infection Prevention, CCA - Disease profiling, CCA - Immuno-pathogenesis, Plastic, Reconstructive and Hand Surgery, Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, D:a:d Study, Group, Castagna, Antonella, the Royal Free Hospital Clinic, Cohort, and the, Insight, Smart, and ESPRIT, Study, Clinicum, Department of Medicine, Herrada, Anthony, University of Copenhagen = Københavns Universitet (UCPH), AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Gastroenterology and Hepatology, Dermatology, ACS - Amsterdam Cardiovascular Sciences, Other Research, Anesthesiology, and Bartlett, John

Subjects
Male, Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors, urologic and male genital diseases, Biochemistry, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Male, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Age Factor, Chronic, STAGE RENAL-DISEASE, PROTEINURIA, virus diseases, 11 Medical And Health Sciences, General Medicine, ASSOCIATION, 6. Clean water, female genital diseases and pregnancy complications, 3. Good health, HIV/AIDS, Medicine, Infection, psychological phenomena and processes, Human, medicine.medical_specialty, Renal function, NEFROPATIAS, chronic kidney disease, risk score model, 12. Responsible consumption, ESPRIT study group, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Clinical Research, D:A:D study group, Intensive care medicine, medicine (all), Molecular Biology, Royal Free Hospital Clinic Cohort, Prevention, Anti-HIV Agent, medicine.disease, Prospective Studie, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Immunology, Kidney Disease, PREDICTION, POSITIVE PERSONS, 030232 urology & nephrology, Sex Factor, SDG 3 – Goede gezondheid en welzijn, Medical and Health Sciences, GLOMERULAR-FILTRATION-RATE, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, INSIGHT study group, HIV Infection, LIFE EXPECTANCY, 030212 general & internal medicine, Renal Insufficiency, Prospective cohort study, Framingham Risk Score, Incidence (epidemiology), adult, age factors, anti-hiv agents, CD4 lymphocyte count, clinical decision-making, comorbidity, female, hiv, hiv infections, hiv seropositivity, humans, incidence, kidney, male, middle aged, prospective studies, renal insufficiency, chronic, risk, risk assessment, sex factors, SMART study group, 6.1 Pharmaceuticals, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Patient Safety, Risk assessment, Biotechnology, Research Article, Settore MED/17 - MALATTIE INFETTIVE, NO, A:D study group [D], General & Internal Medicine, Diabetes mellitus, mental disorders, medicine, EXPOSURE, business.industry, Evaluation of treatments and therapeutic interventions, Cell Biology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, INDIVIDUALS, Good Health and Well Being, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Kidney disease
Abstract

Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD., Editors’ Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled, but not cured, using combination antiretroviral therapy (cART), and, nowadays, the life expectancy of many HIV-positive individuals is similar to that of HIV-negative people. HIV-positive individuals nevertheless experience some illnesses more frequently than HIV-negative people do. For example, up to a third of HIV-positive individuals develop chronic kidney disease (CKD), which is associated with an increased risk of cardiovascular disease and death. Persons with CKD may have an impaired effect of the filtration units in the kidneys that remove waste products and excess water from the blood to make urine, thereby leading to a reduced blood filtration rate (the estimated glomerular filtration rate [eGFR]) and waste product accumulation in the blood. Symptoms of CKD, which rarely occur until the disease is advanced, include tiredness, swollen feet, and frequent urination. Advanced stages of CKD cannot be cured, but its progression can be slowed by, for example, controlling hypertension (high blood pressure) and diabetes (two CDK risk factors) and by adopting a healthy lifestyle. Why Was This Study Done? The burden of CKD may increase among HIV-positive individuals as they age, and clinicians need to know which individuals are at high risk of developing CKD when choosing cART regimens for their patients. In addition, clinicians need to be able to identify those HIV-positive individuals at greatest risk of CKD so that they can monitor them for early signs of kidney disease. Some antiretroviral drugs—for example, tenofovir and atazanavir/ritonavir (a boosted protease inhibitor)—are associated with kidney damage. Clinicians may need to weigh the benefits and risks of giving such potentially nephrotoxic drugs to individuals who already have a high CKD risk. Here, the researchers develop and validate a simple, widely applicable risk score (a risk prediction model) for CKD among HIV-positive individuals and investigate the relationship between CKD and potentially nephrotoxic antiretroviral drugs among individuals with different CKD risk score profiles. What Did the Researchers Do and Find? To develop their CKD risk score, the researchers used clinical and demographic data collected from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study who had an eGFR > 60 ml/min/1.73 m2 and were not taking a potentially nephrotoxic antiretroviral at baseline. During 103,185 person-years of follow-up, 641 individuals developed CKD. Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease predicted CKD. The researchers included these nine factors in their risk score model (which is available online) and defined three risk groups: low (risk score < 0), medium (risk score 0–4), and high (risk score ≥ 5) risk of CKD development in the next five years. Specifically, there was a 1 in 393, 1 in 47, and 1 in 6 chance of developing CKD in the next five years in the low, medium, and high risk groups, respectively. Because some patients started to use potentially nephrotoxic antiretroviral drugs during follow-up, the researchers were able to use their risk score model to calculate how many patients would have to be treated with one of these drugs for an additional patient to develop CKD over five years in each risk group. This “number needed to harm” (NNTH) for patients starting treatment with tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor was 739, 88, and 9 in the low, medium, and high risk groups, respectively. Finally, the researchers validated the accuracy of their risk score in two independent HIV study groups. What Do These Findings Mean? These findings provide a simple, validated risk score for CKD and indicate that the NNTH when starting potentially nephrotoxic antiretrovirals was low among HIV-positive individuals at the highest risk of CKD (i.e., treating just nine individuals with nephrotoxic antiretroviral drugs will likely lead to an additional case of CKD in five years). Although various aspects of the study, including the lack of data on race, limit the accuracy of these findings, these findings highlight the need for monitoring, screening, and chronic disease prevention to minimize the risk of HIV-positive individuals developing diabetes, hypertension, or cardiovascular disease, or becoming coinfected with hepatitis C, all of which contribute to the CKD risk score. Moreover, the development of a tool for estimating an individual’s five-year risk of developing CKD with or without the addition of potentially nephrotoxic antiretroviral drugs will enable clinicians and patients to weigh the benefits of certain antiretroviral drugs against the risk of CKD and make informed decisions about treatment options. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001809. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish) A tool for calculating the CDK risk score developed in this study is available Additional information about the D:A:D study is available, Amanda Mocroft and colleagues develop and validate a model for determining risk of developing chronic kidney disease for individuals with HIV if treated with different antiretroviral therapies.

Published
2015
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30. Turbulence and its effects on the thrust and wake of a porous disc rotor simulator

Author

Blackmore, T. and Bahaj, A.S.

Abstract

Marine current turbines are still in their infancy with many devices at the development stage. Studies are often carried out using small scale laboratory experiments in flumes, towing tanks and numerical simulations to investigate the wakes and performance of scale marine current turbines. However, the characteristics of the inflow turbulence used in such studies is often not fully considered. Tidal flows are highly turbulent with a broad range of eddy sizes and intensities. So differences are expected when predictions of array energy yields are made from towing tanks studies with zero turbulence. This work considers the effects of turbulent eddy size on the thrust and wake behind a porous disc rotor simulator commonly used to represent marine current turbines in small scale experiments. The results show an increase in thrust coefficient with increasing length scale and a corresponding reduction in velocity deficit in the wake. These findings have implications to array special planning and hence energy yields.

Published
2014

31. Australasian Society of Infectious Diseases updated guidelines for the management ofClostridium difficileinfection in adults and children in Australia and New Zealand

Author

Trubiano, J. A., primary, Cheng, A. C., additional, Korman, T. M., additional, Roder, C., additional, Campbell, A., additional, May, M. L. A., additional, Blyth, C. C., additional, Ferguson, J. K., additional, Blackmore, T. K., additional, Riley, T. V., additional, and Athan, E., additional

Published
2016
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32. Turbulence generation and its effect in LES approximations of tidal turbines

Author

Blackmore, T., Batten, W.M.J., and Bahaj, A.S.

Subjects
Nonlinear Sciences::Chaotic Dynamics, Physics::Fluid Dynamics, Physics::Space Physics
Abstract

Tidal flows suitable for the installation of tidal stream turbines are highly turbulent with a broad range of turbulent scales, and intensities of around 10%. It is important to understand how turbulent flows affect the performance and wake profiles for the accurate prediction of the performance of single devices and arrays. Previous studies have considered the effects of turbulence intensity, but the effects of turbulent eddy size have not been investigated. This paper presents a new method for generating turbulence in large eddy simulations of uniform actuator disc rotor models. The advantage of the gridded actuator disc is that the generated turbulence may be controlled, so the effects of turbulence length scale and intensity may be investigated. Initial results show the wake recovery is faster behind a rotor generating larger turbulent length scales and intensities, with a corresponding increase in axial induction and thrust. Therefore turbines may be positioned closer together if they generate more turbulence, increasing the power output of an array for a given area, although the individual device performance may be lower. Future work will consider the effects of free-stream turbulence on the performance and wake profiles of the gridded actuator disc, and validation against experimental data.

Published
2013

33. Identification of complement regulatory domains in human factor H

Author

David Gordon, Richard Kaufman, Blackmore, T., Jeffrey Kwong, and Lublin, D. M.

Subjects
Immunology, Immunology and Allergy
Abstract

Factor H, a regulator of complement activation, contains 20 short consensus repeat (SCR) domains common among the family of C3b/C4b-binding proteins. Chinese hamster ovary cells transfected with cDNA corresponding to the N-terminal tryptic fragment of factor H (containing SCR 1-5 and part of SCR 6) secreted protein with cofactor activity for factor I-dependent cleavage of C3b. A series of deletion mutants, each lacking one of the first five SCR, were constructed, and the supernatants of transfected Chinese hamster ovary cells were tested for cofactor activity. Supernatants of Chinese hamster ovary cells transfected with SCR 1, SCR 4, and SCR 5 deletion mutants retained cofactor function, although the SCR 1 deletion had reduced cofactor activity. Deletion of SCR 2 or 3 totally abolished cofactor activity. Expression and functional analysis of SCR units 1-3, 2-3, and 2-4 demonstrated that the SCR 1-3 unit is sufficient for cofactor activity, but SCR 1-4 is required for full activity. For assays involving cell protection, a construct linking SCR 1-5 to the glycosyl-phosphatidylinositol anchor of decay-accelerating factor was prepared, and stable transfectants were obtained. These cells were protected against complement-mediated cytotoxicity, similarly to decay-accelerating factor- and membrane cofactor protein-transfected cells. These studies define the complement regulatory domains in factor H and suggest that the general complement functional unit for C3 convertase regulation involves three or four consecutive SCR units.

Published
1995
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34. The sensitivity of actuator-disc RANS simulations to turbulence length scale assumptions

Author

Blackmore, T., Batten, W.M.J., Harrison, M.E., and Bahaj, A.S.

Subjects
Physics::Fluid Dynamics
Abstract

It has previously been shown that ambient turbulence affects the results from computational fluid dynamics (CFD) models when using an actuator disc to simulate marine current turbines. The turbulence parameters are often estimated using an empirical equation that is dependent on a turbulence length scale. In most literature this length scale is commonly highlighted as the authors ‘best guess’ with little scientific reasoning. The work presented here investigates the effects of using different length scales on the development of a flow in a circulating water channel. The results showed that the best agreement is achieved with a length scale of one third the channel depth. The obtained turbulence parameters were then used with an actuator disc model. Agreement with experimental data was initially poor as the velocity deficit was severely under predicted. The addition of a turbulence source at the disc improved the agreement with experimental data significantly. It was found that the length scale of the disc turbulence should be the diameter of the holes used on the porous discs for experiments. However, there were still discrepancies between the experimental and model turbulence intensities. A possible cause of this may be that the turbulence intensity added at the disc was under predicted. Further work is needed to establish if better agreement can be achieved by increasing the turbulence at the disc.

Published
2011

36. Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Author

Mocroft, A., Lundgren, J. D., Ross, M., Law, M., Reiss, P., Kirk, O., Smith, C., Wentworth, D., Neuhaus, J., Fux, C. A., Moranne, O., Morlat, P., Johnson, M. A., Ryom, L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Weber, R., Pradier, C., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Kamara, D., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbol Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundstrom, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjaer, J., Sjol, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Kesselring, A. M., Friis-Moller, N., Kowalska, J., Sabin, C., Bruyand, M., Kamara, D. A., Bower, M., Fatkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven C., J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. F., Hoeksema, K., Kleene, M. J., van der Meche, I. B., Toonen, A. J. M., Wijnands, S., van Ogtrop, M. L., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, B. J., Stelma, F. F., Burger, D., Richter, C., van der Berg, J. P., Gisolf, E. H., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., Veenstra, J., Lettinga, K. D., Spelbrink, M., Sulman, H., Witte, E., Peerbooms, P. G. H., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Oudmaijer Sanders, E., Smits, P. H. M., Rosingh, A. W., Verhagen, D. W. M., Geilings, J., van Kasteren, M. E. E., Brouwer, A. E., de Kruijf-van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, J. H., G. M. Buiting, A., Kabel, P. J., Bierman, W. F. W., Sprenger, H. G., Scholvinck, E. H., van Assen, S., Wilting, K. R., Stienstra, Y., de Groot-de Jonge, H., van der Meulen, P. A., de Weerd, D. A., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Hoepelman, A. I. M., Schneider, M. M. E., Mudrikova, T., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Barth, R. E., Wassenberg, M. W. M., van Elst-Laurijssen, D. H. M., Laan, L. M., van Oers-Hazelzet, E. E. B., Patist, J., Vervoort, S., Nieuwenhuis, H. E., Frauenfelder, R., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, M. A., Perenboom, R. M., Bomers, M., de Vocht, J., Elsenburg, L. J. M., Pettersson, A. M., Vandenbroucke-Grauls, C. M. J. E., Ang, C. W., Geelen, S. P. M., Wolfs, T. F. W., Bont, L. J., Nauta, N., Bezemer, D. O., Gras, L., van Sighem, A. I., Smit, C., Zaheri, S., Kimmel, V., Tong, Y., Lascaris, B., van den Boogaard, R., Hoekstra, P., de Lang, A., Berkhout, M., Grivell, S., Jansen, A., de Groot, L., van den Akker, M., Bergsma, D., Lodewijk, C., Meijering, R., Peeck, B., Raethke, M., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Tuijn, E., Veenenberg, L., Woudstra, T., Bakker, Y., de Jong, A., Broekhoven, M., Claessen, E., Rademaker, M. J., Munjishvili, L., Kruijne, E., Tuk, B., Bonnet, F., Dupon, M., Chene, G., Breilh, D., Fleury, H., Malvy, D., Mercie, P., Pellegrin, I., Neau, D., Bouchet, S., Gaborieau, V., Lacoste, D., Tchamgoue, S., Thiebaut, R., Lawson-Ayayi, S., Wittkop, L., Bernard, N., Hessamfar, M., Vandenhende, M. A., Dauchy, F. A., Dutronc, H., Longy-Boursier, M., Duffau, P., Roger Schmeltz, J., Pistone, T., Receveur, M. C., Cazanave, C., Ochoa, A., Vareil, M. O., Pellegrin, J. L., Viallard, J. F., Greib, C., Lazaro, E., Lafon, M. E., Reigadas, S., Trimoulet, P., Molimard, M., Titier, K., Moreau, J. F., Haramburu, F., Miremont-Salame, G., Dupont, A., Gerard, Y., Caunegre, L., Andre, K., Bonnal, F., Farbos, S., Gemain, M. C., Ceccaldi, J., De Witte, S., Courtault, C., Monlun, E., Lataste, P., Meraud, J. P., Chossat, I., Blaizeau, M. J., Conte, V., Decoin, M., Delaune, J., Delveaux, S., Diarra, F., D'Ivernois, C., Frosch, A., Hannapier, C., Lenaud, E., Leleux, O., Le Marec, F., Leray, J., Louis, I., Palmer, G., Pougetoux, A., Sicard, X., Touchard, D., Uwamaliya-Nziyumvira, B., Petoumenos, K., Bendall, C., Moore, R., Edwards, S., Watson, K., Roth, N., Nicholson, J., Bloch, M., Franic, T., Baker, D., Vale, R., Carr, A., Cooper, D., Chuah, J., Ngieng, M., Nolan, D., Skett, J., Calvo, G., Mateu, S., Domingo, P., Sambeat, M. A., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaque, A., Clumeck, N., Necsoi, C., Gennotte, A. F., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, M. C., Semaille, P., Van Laethem, Y., Neaton, J., Bartsch, G., Thompson, G., Luskin-Hawk, R., Telzak, E., Abrams, D. I., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, L. R., Sampson, J., Baxter, J., Cozzi-Lepri, A., Grint, D., Podlekareva, D., Peters, L., Reekie, J., Fischer, A. H., Losso, M., Elias, C., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Colebunders, R., Vandekerckhove, L., Hadziosmanovic, V., Kostov, K., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Larsen, M., Gerstoft, J., Katzenstein, T., Hansen, A. -B. E., Skinhoj, P., Pedersen, C., Ostergaard, L., Zilmer, K., Smidt, J., Ristola, M., Katlama, C., Viard, J. -P., Girard, P. -M., Livrozet, J. M., Vanhems, P., Rockstroh, J., Schmidt, R., van Lunzen, J., Degen, O., Stellbrink, H. J., Staszewski, S., Bickel, M., Kosmidis, J., Gargalianos, P., Xylomenos, G., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Sambatakou, H., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Maayan, S., Vella, S., Esposito, R., Mazeu, I., Mussini, C., Arici, C., Pristera, R., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Chirianni, A., Montesarchio, E., Gargiulo, M., Antonucci, G., Testa, A., Narciso, P., Vlassi, C., Zaccarelli, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Zeltina, I., Chaplinskas, S., Hemmer, R., Staub, T., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Horban, A., Bakowska, E., Grzeszczuk, A., Flisiak, R., Boron-Kaczmarska, A., Pynka, M., Parczewski, M., Beniowski, M., Mularska, E., Trocha, H., Jablonowska, E., Malolepsza, E., Wojcik, K., Antunes, F., Doroana, M., Caldeira, L., Mansinho, K., Maltez, F., Duiculescu, D., Rakhmanova, A., Zakharova, N., Buzunova, S., Jevtovic, D., Mokras, M., Stanekova, D., Tomazic, J., Gonzalez-Lahoz, J., Soriano, V., Labarga, P., Medrano, J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Miro, J. M., Gutierrez, M., Mateo, G., Karlsson, A., Flamholc, L., Ledergerber, B., Francioli, P., Cavassini, M., Hirschel, B., Boffi, E., Furrer, H., Battegay, M., Elzi, L., Kravchenko, E., Chentsova, N., Frolov, V., Kutsyna, G., Servitskiy, S., Krasnov, M., Barton, S., Johnson, A. M., Mercey, D., Murphy, M., Weber, J., Scullard, G., Fisher, M., Leen, C., Morfeldt, L., Thulin, G., Akerlund, B., Koppel, K., Hakangard, C., Moroni, M., Angarano, G., Antinori, A., Armignacco, O., Castelli, F., Cauda, Roberto, Di Perri, G., Iardino, R., Ippolito, G., Perno, C. F., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bonora, S., Borderi, M., Capobianchi, R., Ceccherini- Silberstein, F., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rusconi, S., Cicconi, P., Formenti, T., Galli, L., Lorenzini, P., Giacometti, A., Costantini, A., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Cassola, G., Viscoli, G., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Bonfanti, P., Caramma, I., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Puzzolante, C., Abrescia, N., Guida, M. 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J., Mooka, B., Mamorksy, M. G., Agmon-Levin, N., Karplus, R., Shahar, E., Biglino, A., De Gioanni, M., Montroni, M., Raise, E., Honda, M., Ishisaka, M., Caplinskas, S., Uzdaviniene, V., Schmit, J. C., Mills, G. D., Blackmore, T., Masters, J. A., Morgan, J., Pithie, A., Brunn, J., Ormasssen, V., La Rosa, A., Guerra, O., Espichan, M., Gutierrez, L., Mendo, F., Salazar, R., Knytz, B., Kwiatkowski, J., Castro, R. S., Horta, A., Miranda, A. C., Pinto, I. V., Vera, J., Vinogradova, E., Yakovlev, A., Wood, R., Orrel, C., Arnaiz, J. A., Carrillo, R., Dalmau, D., Jordano, Q., Knobel, H., Larrousse, M., Moreno, J. S., Oretaga, E., Pena, J. N., Spycher, R., Bottone, S., Christen, A., Franc, C., Furrer, H. J., Gayet-Ageron, A., Genne, D., Hochstrasser, S., Moens, C., Nuesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Palfreeman, A. J., Peters, B. S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, A., Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, I. G., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, D., Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, D. E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Clark, C., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, E., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, D. T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez-Barradas, M. C., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sampson, J. H., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheble-Hall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Telzak, E. E., Thompson, M. A., Thompson, S., Ting Hong Bong, C., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, B. H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, A. M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Cauda R. (ORCID:0000-0002-1498-4229)

Abstract

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events)

Published
2015

37. Surveillance for the 2009 pandemic influenza A (H1N1) virus and seasonal influenza viruses--New Zealand, 2009

Author

Huang, Q.S., Bandaranayake, D., Lopez, L.D., Pirie, R., Peacey, M., Hall, R., Bocacao, J., Adlam, B., Hope, V., Croxson, M., Basu, I., Roberts, S., Lindeman, J., Gale, C., Mansell, C., Rooker, S., Olsen, L., Blackmore, T., Jennings, L., Werna, A., Barrett, K., Hunt, D., Jacobs, M., McGrath, F., and Mackereth, G.

Subjects
Development and progression, Demographic aspects, Forecasts and trends, Market trend/market analysis, Epidemics -- New Zealand -- Demographic aspects -- Development and progression, Sentinel surveillance -- 2009 AD -- Development and progression, Public health -- Forecasts and trends -- 2009 AD, Influenza -- Development and progression -- Demographic aspects -- 2009 AD, Sentinel health events -- 2009 AD -- Development and progression
Abstract

The 2009 pandemic influenza A (H1N1) virus,* which was first identified in the United States (1) and Mexico (2), was imported into New Zealand by a high school group returning [...]

Published
2009

38. Inlet grid-generated turbulence for large-eddy simulations

Author

Blackmore, T., Batten, W. M. J., Bahaj, A. S., Blackmore, T., Batten, W. M. J., and Bahaj, A. S.

Abstract

A new technique of generating turbulence in large-eddy simulations (LES) has been investigated and results compared with previous studies for validation. The proposed gridInlet technique uses a grid pattern on the inlet boundary patch to produce grid-generated turbulence as used in wind tunnel experiments. This allows the turbulence integral length scale to be controlled by changing the grid size, while the turbulence intensity is controlled by changing the inlet distance. The objective of this paper is to investigate domain and mesh requirements to implement the gridInlet technique. This technique is most suited to studies on the influence of high-intensity isotropic turbulence on objects, particularly if comparisons are to be made to experimental data obtained with grid-generated turbulence.

Published
2013
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45. Reply

Author

Raymond, N. J., primary, Blackmore, T. K., additional, Humble, M. W., additional, and Jones, M. R., additional

Published
2007
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