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1. Viral hepatitis cascade of care among adults living with HIV in Asia-Pacific

Author

Rupasinghe, D., Choi, J.Y., Kumarasamy, N., Pujari, S., Ly, P.S., Merati, T.P., Lee, M.P., Nguyen, K.V., Kiertiburanakul, S., Do, C.D., Avihingsanon, A., Ross, J., and Jiamsakul, A.

Subjects
Comorbidity -- Influence, Hepatitis B -- Development and progression -- Care and treatment, Medical care -- Quality management, Hepatitis C -- Development and progression -- Care and treatment, HIV infection -- Complications and side effects -- Care and treatment, Health
Abstract

Background: Data on viral hepatitis (VH) diagnosis, treatment and cure rates among PLHIV from the Asia-Pacific region are limited. With targets set to eliminate VH as a global epidemic by [...]

Published
2021
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2. Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity : An Observational Study

Author

Romo, M.L., Patel, R.C., Edwards, J.K., Humphrey, J.M., Musick, B.S., Bernard, C., Maina, M.W., Brazier, E., Castelnuovo, B., Penner, J., Wyka, K., Cardoso, S.W., Ly, P.S., Kunzekwenyika, C., Cortés, C.P., Panczak, R., Kelvin, E.A., Wools-Kaloustian, K.K., Nash, D., Khol, V., Zhang, F.J., Zhao, H.X., Han, N., Lee, M.P., Li, P.C.K., Lam, W., Wong, H.Y., Kumarasamy, N., Ezhilarasi, C., Pujari, S., Joshi, K., Gaikwad, S., Chitalikar, A., Merati, T.P., Wirawan, D.N., Yuliana, F., Yunihastuti, E., Imran, D., Widhani, A., Tanuma, J., Oka, S., Nishijima, T., Choi, J.Y., Na, S., Kim, J.M., Gani, Y.M., Rudi, N.B., Azwa, I., Kamarulzaman, A., Syed Omar, S.F., Ponnampalavanar, S., Ditangco, R., Pasayan, M.K., Mationg, M.L., Chan, Y.J., Ku, W.W., Ke, E., Wu, P.C., Ng, O.T., Lim, P.L., Lee, L.S., Yap, J.K., Avihingsanon, A., Gatechompol, S., Phanuphak, P., Phadungphon, C., Kiertiburanakul, S., Phuphuakrat, A., Chumla, L., Sanmeema, N., Chaiwarith, R., Sirisanthana, T., Praparattanapan, J., Nuket, K., Khuwuwan, S., Kantipong, P., Kambua, P., Nguyen, K.V., Bui, H.V., Nguyen, D.T.H., Nguyen, D.T., Do, C.D., Ngo, A.V., Nguyen, L.T., Sohn, A.H., Ross, J.L., Petersen, B., Law, M.G., Jiamsakul, A., Bijker, R., Rupasinghe, D., Cahn, P., Cesar, C., Fink, V., Sued, O., Dell'Isola, E., Perez, H., Valiente, J., Yamamoto, C., Grinsztejn, B., Veloso, V., Luz, P., de Boni, R., Wagner, S.C., Friedman, R., Moreira, R., Pinto, J., Ferreira, F., Maia, M., de Menezes Succi, R.C., Machado, D.M., de Fátima Barbosa Gouvêa, A., Wolff, M., Rodriguez, M.F., Allendes, G., Pape, J.W., Rouzier, V., Marcelin, A., Perodin, C., Luque, M.T., Padgett, D., Madero, J.S., Ramirez, B.C., Belaunzaran, P., Vega, Y.C., Gotuzzo Herencia, José Eduardo, Mejía Cordero, Fernando Alonso, Carriquiry, G., McGowan, C.C., Shepherd, B.E., Sterling, T., Jayathilake, K., Person, A.K., Rebeiro, P.F., Castilho, J., Duda, S.N., Maruri, F., Vansell, H., Jenkins, C., Kim, A., Lotspeich, S., Pélagie, N., Gateretse, P., Munezero, J., Nitereka, V., Niyongabo, T., Twizere, C., Bukuru, H., Nahimana, T., Baransaka, E., Barasukana, P., Kabanda, E., Manirakiza, M., Ndikumwenayo, F., Biziragusenyuka, J., Munezero, A.M.M., Nforniwe, D.N., Ajeh, R., Ngamani, M.L., Dzudie, A., Mbuh, A., Amadou, D., Yone, E.W.P., Kendowo, E., Akele, C., Clever, A., Kitetele, F., Lelo, P., Tabala, M., Ekembe, C., Kaba, D., Diafouka, M., Ekat, M.H., Nsonde, D.M., Mafoua, A., Christ, M.N., Igirimbabazi, J., Ayinkamiye, N., Uwineza, P., Ndamijimana, E., Habarurema, E., Nyiraneza, M.L., Nyiransabimana, M.L., Tuyisenge, L., Shyaka, C., Kankindi, C., Uwakijijwe, B., Ingabire, M.G., Ndumuhire, J., Nyirabahutu, M.G., Muyango, F., Bihibindi, J.C., Uwamahoro, O., Ndoli, Y., Nsanzimana, S., Mugwaneza, P., Remera, E., Umumararungu, E., Rwibasira, G.N., Habimana, D.S., Gasana, J., Kanyabwisha, F., Kubwimana, G., Muhoza, B., Munyaneza, A., Murenzi, G., Musabyimana, F., Umwiza, F., Ingabire, C., Tuyisenge, P., Butera, A.M., Kabahizi, J., Rurangwa, E., Feza, R., Mukashyaka, E., Benekigeri, C., Musaninyange, J., Adedimeji, A., Anastos, K., Dilorenzo, M., Murchison, L., Ross, J., Yotebieng, M., Addison, D., Jones, H., Kulkarni, S., Tymejczyk, O., Elul, B., Cai, X., Dong, A., Hoover, D., Kim, H.-Y., Li, C., Shi, Q., Lancaster, K., Kuniholm, M., Edmonds, A., Parcesepe, A., Edwards, J., Keiser, O., Kimmel, A., Diero, L., Ayaya, S., Sang, E., Bukusi, E., Mulwa, E., Nyanaro, G., Kasozi, C., Ssemakadde, M., Bwana, M.B., Muyindike, W., Byakwaga, H., Kanyesigye, M., Semeere, A., Matovu, J.M., Nalugoda, F., Wasswa, F.X., Kazyoba, P., Mayige, M., Lyamuya, R.E., Mayanga, F., Ngonyani, K., Lwali, J., Urassa, M., Nyaga, C., Machemba, R., Yiannoutsos, C., Vreeman, R., Syvertsen, J., Kantor, R., Martin, J., Wenger, M., Cohen, C., Kulzer, J., Maartens, G., Bolton, C., Wood, R., Sipambo, N., Tanser, F., Boulle, A., Fatti, G., Mbewe, S., Singh, E., Chimbetete, C., Technau, K., Eley, B., Muhairwe, J., Rafael, I., Fox, M.P., Prozesky, H., Anderegg, N., Ballif, M., Ostinelli, C.H.D., Egger, M., Fenner, L., Haas, A., Hossmann, S., Rohner, E., Riou, J., Skrivankova, V., Smith, L., Taghavi, K., von Groote, P., Wandeler, G., Zaniewski, E., Zürcher, K., Anderson, K., Cornell, M., Davies, M.-A., Iyun, V., Johnson, L., Kassanjee, R., Kehoe, K., Kubjane, M., Maxwell, N., Nyakato, P., Patten, G., Tlali, M., Tsondai, P., de Waal, R., and International epidemiology Databases to Evaluate AIDS (IeDEA)

Subjects
Adult, medicine.medical_specialty, Prevention, policy, and public health, Adolescent, Pyridones, Reproductive age, HIV Infections, Choice Behavior, Article, Piperazines, chemistry.chemical_compound, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Epidemiology, Oxazines, Internal Medicine, Medicine, Humans, Maternal Health Services, Cumulative incidence, HIV Integrase Inhibitors, 610 Medicine & health, Developing Countries, Health equity, business.industry, HIV, Contraceptives, General Medicine, Middle Aged, medicine.disease, Antiretroviral therapy, Regimen, Pharmaceutical Preparations, chemistry, Dolutegravir, Observational study, Female, Age groups, Safety, business, Heterocyclic Compounds, 3-Ring, 360 Social problems & social services, Demography, Cohort study
Abstract

BACKGROUND The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN Observational cohort study. SETTING 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS 134��672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE National Institutes of Health.

Published
2021
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5. Atherosclerotic cardiovascular disease screening and management protocols among adult HIV clinics in Asia

Author

Boettiger, D.C., primary, Law, M.G., additional, Ross, J., additional, Huy, B.V., additional, Heng, B.S.L., additional, Ditangco, R., additional, Kiertiburanakul, S., additional, Avihingsanon, A., additional, Cuong, D.D., additional, Kumarasamy, N., additional, Kamarulzaman, A., additional, Ly, P.S., additional, Yunihastuti, E., additional, Parwati Merati, T., additional, Zhang, F., additional, Khusuwan, S., additional, Chaiwarith, R., additional, Lee, M.P., additional, Sangle, S., additional, Choi, J.Y., additional, Ku, W.W., additional, Tanuma, J., additional, Ng, O.T., additional, Sohn, A.H., additional, Wester, C.W., additional, Nash, D., additional, Mugglin, C., additional, and Pujari, S., additional

Published
2020
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6. Planar laser-induced fluorescence imaging of shock-tube flows with vibrational nonequilibrium

Author

McMillin, B.K., Lee, M.P., and Hanson, R. K.

Subjects
Fluorescence -- Research, Lasers -- Research, Nitric oxide -- Research, Shock waves -- Analysis, Aerodynamics, Supersonic -- Research, Aerospace and defense industries, Business
Abstract

This study applied planar laser-induced flourescence (PLIF) imaging to nitric oxide, NO, in nonreacting shock-tube flows with vibrational nonequilibrium. Single-shot PLIF images of both normal incident and reflected shocks in dilute mixtures of NO in argon are examined, and the vibrational relaxation rates of NO agrees with known relaxation rates. The results show that PLIF imaging is a promising diagnostic technique for high-speed flows because it can simultaneously probe shock-wave structure and vibrational nonequilibrium throughout the flowfield with excellent spatial and temporal resolution.

Published
1992

8. Dynamic stereo microscopy for studying particle sedimentation

Author

Lee, M.P., Gibson, G.M., Phillips, D., Padgett, M.J., and Tassieri, M.

Subjects
genetic structures, sense organs
Abstract

We demonstrate a new method for measuring the sedimentation\ud of a single colloidal bead by using a combination of optical tweezers and a stereo microscope based on a spatial light modulator. We use optical tweezers to raise a micron-sized silica bead to a fixed height and then release it to observe its 3D motion while it sediments under gravity. This experimental procedure provides two independent measurements of bead diameter and a measure of Faxén’s correction, where the motion changes due to presence of the boundary.

Published
2014

9. Efficacy and safety of efavirenz 400 mg daily versus 600 mg daily: 96-week data from the randomised, double-blind, placebo-controlled, non-inferiority ENCORE1 study

Author

Carey, D., Puls, R., Amin, J., Losso, M., Phanupak, P., Foulkes, S., Mohapi, L., Crabtree-Ramirez, B., Jessen, H., Kumar, S., Winston, A., Lee, M.P., Belloso, W., Cooper, D.A., Emery, S., Nolan, D., Carey, D., Puls, R., Amin, J., Losso, M., Phanupak, P., Foulkes, S., Mohapi, L., Crabtree-Ramirez, B., Jessen, H., Kumar, S., Winston, A., Lee, M.P., Belloso, W., Cooper, D.A., Emery, S., and Nolan, D.

Abstract

Background The week 48 primary analysis of the ENCORE1 trial established the virological non-inferiority and safety of efavirenz 400 mg compared with the standard 600 mg dose, combined with tenofovir and emtricitabine, as first-line HIV therapy. This 96-week follow-up of the trial assesses the durability of efficacy and safety of this treatment over 96 weeks. Methods ENCORE1 was a double-blind, placebo-controlled, non-inferiority trial done at 38 clinical sites in 13 countries. HIV-infected adult patients (≥16 years of age) with no previous antiretroviral therapy, a CD4 cell count of 50–500 cells per μL, and plasma HIV-1 viral load of at least 1000 copies per mL were randomly assigned (1:1) by an electronic case report form to receive fixed-dose daily tenofovir 300 mg and emtricitabine 200 mg plus efavirenz either 400 mg daily or 600 mg daily. Participants, physicians, and all other trial staff were masked to treatment assignment. Randomisation was stratified by HIV-1 viral load at baseline (≤ or >100 000 copies per mL). The primary endpoint was the difference in the proportions of patients in the two treatment groups with a plasma HIV-1 viral load below 200 copies per mL at week 96. Treatment groups were deemed to be non-inferior if the lower limit of the 95% CI for the difference in viral load was above −10% by modified intention-to-treat analysis. Non-inferiority was assessed in the modified intention-to-treat, per-protocol, and non-completer=failure (NC=F) populations. Adverse events and serious adverse events were summarised by treatment group. This study is registered with ClinicalTrials.gov, number NCT01011413. Findings Between Aug 24, 2011, and March 19, 2012, 636 eligible participants were enrolled and randomly assigned to the two treatment groups (324 to efavirenz 400 mg and 312 to efavirenz 600 mg). The intention-to-treat population who received at least one dose of study drug comprised 630 patients: 321 in the efavirenz 400 mg group and 309 in the efavir

Published
2015

10. Temporal trends of time to antiretroviral treatment initiation, interruption and modification: Examination of patients diagnosed with advanced HIV in Australia.

Author

Kelly M., Donohue W., Moore R., Edwards S., Agrawal S., Vincent T., Allen D., Little J.L., Smith D.E., Mincham C., Baker D., Ieroklis V., Templeton D.J., O'Connor C.C., Phan S., Jackson E., McCallum K., Grotowski M., Taylor S., Carr A., Lee F., Hesse K., Sinn K., Norris R., Finlayson R., Prone I., Patel A., Varma R., Shakeshaft J., Brown K., McGrath C., Halligan S., Wray L., Read P., Lu H., Couldwell D., Furner V., Fernando S., Chuah J., Watson J., Lawrence C., Mulhall B., McManus H., Bendall C., Boyd M.A., Ryder N., Payne R., Russell D., Doyle-Adams S., Sowden D., Taing K., McGill K., Orth D., Youds D., Gibson A., Magon H., Kamarulzaman A., Choi J.Y., Vannary B., Ditangco R., Tsukada K., Pujari S., Makane A., Ng O.T., Sasisopin A.J., Liddle R., Locke P., Roth N.J., Lau H., Read T., Silvers J., Zeng W., Korman T., Watson K., Bryant M., Price S., Giles M., Hoy J., Williams J., Nolan D., Robinson J., Morwood K., Roth N., Choong K., Li P.C.K., Lee M.P., Vanar S., Faridah S., Wright S.T., Law M.G., Cooper D., Keen P., McDonald A., Middleton M., Woolley I., Dickson B., Petoumenos K., Ellis D., Bloch M., Kelly M., Donohue W., Moore R., Edwards S., Agrawal S., Vincent T., Allen D., Little J.L., Smith D.E., Mincham C., Baker D., Ieroklis V., Templeton D.J., O'Connor C.C., Phan S., Jackson E., McCallum K., Grotowski M., Taylor S., Carr A., Lee F., Hesse K., Sinn K., Norris R., Finlayson R., Prone I., Patel A., Varma R., Shakeshaft J., Brown K., McGrath C., Halligan S., Wray L., Read P., Lu H., Couldwell D., Furner V., Fernando S., Chuah J., Watson J., Lawrence C., Mulhall B., McManus H., Bendall C., Boyd M.A., Ryder N., Payne R., Russell D., Doyle-Adams S., Sowden D., Taing K., McGill K., Orth D., Youds D., Gibson A., Magon H., Kamarulzaman A., Choi J.Y., Vannary B., Ditangco R., Tsukada K., Pujari S., Makane A., Ng O.T., Sasisopin A.J., Liddle R., Locke P., Roth N.J., Lau H., Read T., Silvers J., Zeng W., Korman T., Watson K., Bryant M., Price S., Giles M., Hoy J., Williams J., Nolan D., Robinson J., Morwood K., Roth N., Choong K., Li P.C.K., Lee M.P., Vanar S., Faridah S., Wright S.T., Law M.G., Cooper D., Keen P., McDonald A., Middleton M., Woolley I., Dickson B., Petoumenos K., Ellis D., and Bloch M.

Abstract

Introduction: HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naive, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. Method(s): We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis.We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. Result(s): Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Conclusion(s): Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods.We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods.:Copyright © 2015 Wright ST et al; licensee International AIDS Society.

Published
2015

11. HIV and aging: Insights from the Asia Pacific HIV Observational Database (APHOD).

Author

Lawrence C., Silvers J., Zeng W., Watson K., Bryant M., Price S., Woolley I., Korman T., Williams J., Nolan D., Skett J., Robinson J., Mean C.V., Saphonn V., Vohith K., Zhang F.J., Li P.C.K., Lee M.P., Kumarasamy N., Saghayam S., Ezhilarasi C., Pujari S., Joshi K., Makane A., Merati T.P., Wirawan D.N., Yuliana F., Yunihastuti E., Imran D., Widhani A., Oka S., Tanuma J., Nishijima T., Choi J.Y., Na S., Kim J.M., Lee C.K.C., Sim B.L.H., David R., Syed Omar S.F., Azwa I., Ditangco R., Uy E., Bantique R., Wong W.W., Ku W.W., Wu P.C., Ng O.T., Lim P.L., Lee L.S., Tan M.T., Phanuphak P., Ruxrungtham K., Avihingsanon A., Chusut P., Kiertiburanakul S., Sungkanuparph S., Chumla L., Sanmeema N., Chaiwarith R., Sirisanthana T., Kotarathititum W., Praparattanapan J., Kantipong P., Kambua P., Ratanasuwan W., Sriondee R., Nguyen V.K., Bui V.H., Cao T.T., Pham T.T., Cuong D.D., Ha H.L., Sohn A.H., Durier N., Petersen B., Jiamsakul A., Boettiger D., Kelly M., Gibson A., Magon H., Donohue W., Moore R., Edwards S., Han N., Wright S.T., O'Connor C.C., Hoy J., Ponnampalavanar S., Grotowski M., Zhao H.X., Kamarulzaman A., Ellis D., Bloch M., Franic T., Agrawal S., McCann L., Cunningham N., Vincent T., Allen D., Little J.L., Smith D., Gray C., Baker D., Vale R., Templeton D.J., Dijanosic C., Jackson E., McCallum K., Taylor S., Cooper D.A., Carr A., Lee F., Hesse K., Sinn K., Norris R., Finlayson R., Prone I., Shakeshaft J., Brown K., McGrath C., McGrath V., Halligan S., Wray L., Read P., Lu H., Couldwell D., Furner V., Watson J., Giles M., Mulhall B., Law M., Petoumenos K., McManus H., Bendall C., Boyd M., Kulatunga A., Knibbs P., Chuah J., Ngieng M., Dickson B., Russell D., Downing S., Sowden D., Broom J., Taing K., Johnston C., McGill K., Orth D., Youds D., Liddle R., Locke P., Roth N.J., Nicolson J., Lau H., Read T., Lawrence C., Silvers J., Zeng W., Watson K., Bryant M., Price S., Woolley I., Korman T., Williams J., Nolan D., Skett J., Robinson J., Mean C.V., Saphonn V., Vohith K., Zhang F.J., Li P.C.K., Lee M.P., Kumarasamy N., Saghayam S., Ezhilarasi C., Pujari S., Joshi K., Makane A., Merati T.P., Wirawan D.N., Yuliana F., Yunihastuti E., Imran D., Widhani A., Oka S., Tanuma J., Nishijima T., Choi J.Y., Na S., Kim J.M., Lee C.K.C., Sim B.L.H., David R., Syed Omar S.F., Azwa I., Ditangco R., Uy E., Bantique R., Wong W.W., Ku W.W., Wu P.C., Ng O.T., Lim P.L., Lee L.S., Tan M.T., Phanuphak P., Ruxrungtham K., Avihingsanon A., Chusut P., Kiertiburanakul S., Sungkanuparph S., Chumla L., Sanmeema N., Chaiwarith R., Sirisanthana T., Kotarathititum W., Praparattanapan J., Kantipong P., Kambua P., Ratanasuwan W., Sriondee R., Nguyen V.K., Bui V.H., Cao T.T., Pham T.T., Cuong D.D., Ha H.L., Sohn A.H., Durier N., Petersen B., Jiamsakul A., Boettiger D., Kelly M., Gibson A., Magon H., Donohue W., Moore R., Edwards S., Han N., Wright S.T., O'Connor C.C., Hoy J., Ponnampalavanar S., Grotowski M., Zhao H.X., Kamarulzaman A., Ellis D., Bloch M., Franic T., Agrawal S., McCann L., Cunningham N., Vincent T., Allen D., Little J.L., Smith D., Gray C., Baker D., Vale R., Templeton D.J., Dijanosic C., Jackson E., McCallum K., Taylor S., Cooper D.A., Carr A., Lee F., Hesse K., Sinn K., Norris R., Finlayson R., Prone I., Shakeshaft J., Brown K., McGrath C., McGrath V., Halligan S., Wray L., Read P., Lu H., Couldwell D., Furner V., Watson J., Giles M., Mulhall B., Law M., Petoumenos K., McManus H., Bendall C., Boyd M., Kulatunga A., Knibbs P., Chuah J., Ngieng M., Dickson B., Russell D., Downing S., Sowden D., Broom J., Taing K., Johnston C., McGill K., Orth D., Youds D., Liddle R., Locke P., Roth N.J., Nicolson J., Lau H., and Read T.

Abstract

Objectives: The proportion of people living with HIV/AIDS in the ageing population (>50 years old) is increasing. We aimed to explore the relationship between older age and treatment outcomes in HIV-positive persons from the Asia Pacific region. Method(s): Patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) were included in the analysis. We used survival methods to assess the association between older age and all-cause mortality, as well as time to treatment modification. We used regression analyses to evaluate changes in CD4 counts after combination antiretroviral therapy (cART) initiation and determined the odds of detectable viral load, up to 24 months of treatment. Result(s): A total of 7142 patients were included in these analyses (60% in TAHOD and 40% in AHOD), of whom 25% were >50 years old. In multivariable analyses, those aged >50 years were at least twice as likely to die as those aged 30-39 years [hazard ratio (HR) for 50-59 years: 2.27; 95% confidence interval (CI) 1.34-3.83; HR for >60 years: 4.28; 95% CI 2.42-7.55]. The effect of older age on CD4 count changes was insignificant (p-trend=0.06). The odds of detectable viral load after cART initiation decreased with age (p-trend=<0.0001). The effect of older age on time to first treatment modification was insignificant (p-trend=0.21). We found no statistically significant differences in outcomes between AHOD and TAHOD participants for all endpoints examined. Conclusion(s): The associations between older age and typical patient outcomes in HIV-positive patients from the Asia Pacific region are similar in AHOD and TAHOD. Our data indicate that 'age effects' traverse the resource-rich and resource-limited divide and that future ageing-related findings might be applicable to each setting.Copyright © 2014 British HIV Association.

Published
2015

12. A multi-modal stereo microscope based on a spatial light modulator

Author

Lee, M.P., Gibson, G.M., Bowman, R., Bernet, S., Ritsch-Marte, M., Phillips, David, and Padgett, M.J.

Subjects
ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION
Abstract

Spatial Light Modulators (SLMs) can emulate the classic microscopy techniques, including differential interference (DIC) contrast and (spiral) phase contrast. Their programmability entails the benefit of flexibility or the option to multiplex images, for single-shot quantitative imaging or for simultaneous multi-plane imaging (depth-of-field multiplexing). We report the development of a microscope sharing many of the previously demonstrated capabilities, within a holographic implementation of a stereo microscope. Furthermore, we use the SLM to combine stereo microscopy with a refocusing filter and with a darkfield filter. The instrument is built around a custom inverted microscope and equipped with an SLM which gives various imaging modes laterally displaced on the same camera chip. In addition, there is a wide angle camera for visualisation of a larger region of the sample.

Published
2013

13. Rates and factors associated with major modifications to First-Line combination antiretroviral therapy: Results from the Asia-Pacific region

Author

Wainberg, M., Wright, S., Boyd, M.A., Yunihastuti, E., Law, M., Sirisanthana, T., Hoy, J., Pujari, S., Lee, M.P., Petoumenos, K., Nolan, D., Wainberg, M., Wright, S., Boyd, M.A., Yunihastuti, E., Law, M., Sirisanthana, T., Hoy, J., Pujari, S., Lee, M.P., Petoumenos, K., and Nolan, D.

Abstract

Background In the Asia-Pacific region many countries have adopted the WHO’s public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region. Methods We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country’s per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class. Results A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44–0.52), 0.33 (0.30–0.36) and 0.21 (0.18–0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. Conclusions Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increa

Published
2013

14. Intelligent agents for an Internet-based global crisis communication system

Author

Goh, O.S., Fung, C.C., Lee, M.P., Goh, O.S., Fung, C.C., and Lee, M.P.

Abstract

In times of crisis, an effective communication mechanism is paramount in providing accurate and timely information to the community. Recent examples are the outbreak of SARS, bird flu, mad cow diseases, September 11 attacks and the 2004 tsunamis. Such events have illustrated the importance of an effective and efficient crisis communication system. In this paper, it is proposed the incorporation of an intelligent agent software robot into a crisis communication portal (CCNet) in order to send alert news to subscribed users via email and others mobile services such as Short Message Service (SMS), Multimedia Messaging Service (MMS) and General Packet Radio Services (GPRS). The proposed system consists of the integration of an intelligent conversation agent that is employed to gain trust from the users of the portal and an Automated Knowledge Extraction Agent (AKEA), which retrieves first hand information from relevant sources such as WHO.org, CBC Canada, info.gov.hk and Sars.gov.sg.

Published
2005

17. Optical shield: measuring viscosity of turbid fluids using optical tweezers

Author

Lee, M.P., Curran, A., Gibson, G.M., Tassieri, M., Heckenberg, N.R., and Padgett, M.J.

Subjects
Condensed Matter::Quantum Gases
Abstract

The viscosity of a fluid can be measured by tracking the motion of a suspended micron-sized particle trapped by optical tweezers. However, when the particle density is high, additional particles entering the trap compromise the tracking procedure and degrade the accuracy of the measurement. In this work we introduce an additional Laguerre–Gaussian, i.e. annular, beam surrounding the trap, acting as an optical shield to exclude contaminating particles.

19. Preliminary metallogenic map of North America: a listing of deposits by commodity.

Author

Lee M.P., Guild P.W., Schruben P.G., Lee M.P., Guild P.W., and Schruben P.G.

Abstract

The 4215 deposits shown on the metallogenic map are listed by commodity, with the country, deposit name, deposit type, size, age of mineralisation and indication of size. The most frequently occurring commodity by number of occurrences is gold, followed by copper, silver, lead and zinc. In addition to the USA, Canada and Mexico, the listing also covers Central America and the Caribbean., The 4215 deposits shown on the metallogenic map are listed by commodity, with the country, deposit name, deposit type, size, age of mineralisation and indication of size. The most frequently occurring commodity by number of occurrences is gold, followed by copper, silver, lead and zinc. In addition to the USA, Canada and Mexico, the listing also covers Central America and the Caribbean.

20. The Conterminous United States Mineral Assessment Programme - background information to accompany folio of geologic, geophysical, geochemical, mineral-occurrence, mineral-resource potential, and mineral-production maps of the Charlotte 1 deg. x 2 deg. quadrangle, North Carolina and South Carolina.

Author

Gair J.E, Daniels D.L., DeYoung J.H., Goldsmith R., Griffitts W.R., Lee M.P., Gair J.E, Daniels D.L., DeYoung J.H., Goldsmith R., Griffitts W.R., and Lee M.P.

Abstract

The folios included in this study are a geological map, four geophysical maps, geochemical maps, mineral occurrence maps, mineral-resource potential maps and mineral production maps of the area. A Bouguer gravity survey showed a distinct northwest-trending, northwest decreasing gradient which is part of the major gravity gradient that extends the length of the Appalachian Mountains. The geochemical surveys, based on 2600 heavy mineral concentrate samples obtained from stream sediments, showed widespread tin mineralisation, mainly westward from the Kings Mountain belt; cobalt east of Gaffney, SC and cobalt associated with niobium south of Salisbury NC; and base metal mineralisation in the northeast corner of the quadrangle. Geophysical anomalies have not been used to define mineral resource potential. The presence of certain minerals in the concentrate samples has been a factor in determining resource potential, especially the presence of gold, scheelite and monazite., The folios included in this study are a geological map, four geophysical maps, geochemical maps, mineral occurrence maps, mineral-resource potential maps and mineral production maps of the area. A Bouguer gravity survey showed a distinct northwest-trending, northwest decreasing gradient which is part of the major gravity gradient that extends the length of the Appalachian Mountains. The geochemical surveys, based on 2600 heavy mineral concentrate samples obtained from stream sediments, showed widespread tin mineralisation, mainly westward from the Kings Mountain belt; cobalt east of Gaffney, SC and cobalt associated with niobium south of Salisbury NC; and base metal mineralisation in the northeast corner of the quadrangle. Geophysical anomalies have not been used to define mineral resource potential. The presence of certain minerals in the concentrate samples has been a factor in determining resource potential, especially the presence of gold, scheelite and monazite.

21. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Hidemi Ito, Stephen K. Van Den Eeden, Abdisamad M. Ibrahim, Ching C. Lau, Preetha Rajaraman, Gloria M. Petersen, Judith Hoffman-Bolton, Colin P.N. Dinney, Chang Hyun Kang, Melinda C. Aldrich, Mark P. Purdue, Xiao-Ou Shu, William J. Blot, Sanjay Shete, Alpa V. Patel, Charles Kooperberg, Paolo Vineis, David Van Den Berg, Chao A. Hsiung, Anthony J. Swerdlow, Qing Lan, Wu Chou Su, Afshan Siddiq, Ulrike Peters, Katia Scotlandi, Sara H. Olson, Kendra Schwartz, Kelly L. Bolton, Chancellor Hohensee, Josep Lloreta, Kevin B. Jacobs, Debra T. Silverman, Rudolf Kaaks, Wei Zheng, Steven Gallinger, Junwen Wang, Angela Carta, Massimo Serra, Petra H.M. Peeters, Victoria L. Stevens, Yasushi Yatabe, Geraldine Cancel-Tassin, Joshua N. Sampson, Young Tae Kim, Graham A. Colditz, Pan-Chyr Yang, Baosen Zhou, Fredrick R. Schumacher, Nicolas Wentzensen, Evelyn Tay, Claudia Maria Hattinger, Chen Wu, Pilar Amiano, Mattias Johansson, Maxwell P. Lee, Christian P. Kratz, Michael B. Cook, Mingfeng Zhang, Kay-Tee Khaw, Jian-Min Yuan, Anne Zeleniuch-Jacquotte, Jinping Jia, Roberto Tirabosco, Jing Ma, Neil E. Caporaso, Christopher A. Haiman, Bu Tian Ji, Adrienne M. Flanagan, Neyssa Marina, Eric J. Jacobs, Sophia S. Wang, Chong-Jen Yu, Edward Giovannucci, Margaret Wrensch, Robert L. Grubb, Bin Zhu, Daniel O. Stram, Manolis Kogevinas, Margaret R. Karagas, Mazda Jenab, Alison M. Mondul, Jun Xu, Preethi S. Raj, Anders Ahlbom, Christine D. Berg, Shelley Niwa, Kala Visvanathan, Loic Le Marchand, Jorge R. Toro, Robert N. Hoover, Heather Spencer Feigelson, Michelle Brotzman, Laurence N. Kolonel, Krista A. Zanetti, Chengfeng Wang, Mary Ann Butler, Ann Truelove, Irene L. Andrulis, Hongbing Shen, H. Dean Hosgood, Ming Shyan Huang, Gee-Chen Chang, Jianjun Liu, John K. Wiencke, Stephanie J. Weinstein, Beatrice Melin, Kouya Shiraishi, Zhihua Yin, Lee E. Moore, Börje Ljungberg, Jolanta Lissowska, Elizabeth M. Gillanders, M. T. Landi, Cari M. Kitahara, Maria Feychting, Kuan-Yu Chen, Matthias Simon, Brian M. Wolpin, Hemang Parikh, Hannah P. Yang, Graham G. Giles, Alison Johnson, Demetrius Albanes, Carlos González, Brian E. Henderson, Xifeng Wu, Harvey A. Risch, Amy Hutchinson, Christopher Hautman, Constance Chen, Zhibin Hu, Donghui Li, Elio Riboli, Julie E. Buring, Curtis C. Harris, Xu Che, Núria Malats, Roger Henriksson, Rosario Tumino, Joanne S. Colt, Alfredo Carrato, Paolo Boffetta, Maria Pik Wong, Hideo Tanaka, Federico Canzian, Alan D. L. Sihoe, Chien-Jen Chen, Kenneth Muir, Chen Ying, Qincheng He, Melissa C. Southey, Marc Sanson, Victoria K. Cortessis, Sharon A. Savage, Wei Hu, Yao Tettey, Daniela S. Gerhard, Sofia Pavanello, Guangwen Cao, H. Barton Grossman, Michael Goggins, Hideo Kunitoh, Peter D. Inskip, Seth P. Lerner, Peter Kraft, David Thomas, Peng Guan, Chung Hsing Chen, I. Shou Chang, Christoffer Johansen, Roberta McKean-Cowdin, Lee J. Helman, Yuh Min Chen, Ana Patiño-García, Pär Stattin, Xiaoping Miao, Tangchun Wu, Jay S. Wunder, Ann W. Hsing, Yu-Tang Gao, Brooke L. Fridley, Tania Carreón, Charles C. Chung, Nan Hu, Yoo Jin Jung, Richard B. Biritwum, Eric J. Duell, Philip R. Taylor, Satu Männistö, Kai Yu, Meredith Yeager, Xia Pu, Vittorio Krogh, Anand P. Chokkalingam, Susan M. Gapstur, W. Ryan Diver, Yuanqing Ye, Keitaro Matsuo, Cecilia Arici, You-Lin Qiao, Alan R. Schned, Dominique S. Michaud, Joanne W. Elena, Christopher Kim, Dongxin Lin, Yun-Chul Hong, Daru Lu, Reina García-Closas, Jonine D. Figueroa, Linda M. Liao, Yi-Long Wu, Heiner Boeing, Mark Lathrop, Göran Hallmans, Elizabeth A. Holly, Carol Giffen, Andrew A. Adjei, Consol Serra, Anne Tjønneland, Joseph F. Fraumeni, Alisa M. Goldstein, Ruth C. Travis, Rebecca Troisi, Dalsu Baris, Nalan Gokgoz, Olivier Cussenot, Xiang Deng, Yeul Hong Kim, Malin Sund, Sonja I. Berndt, E. David Crawford, Edward D. Yeboah, Sook Whan Sung, Françoise Clavel-Chapelon, Woon-Puay Koh, Nilgun Kurucu, Richard B. Hayes, Ashish M. Kamat, Beata Peplonska, Laurie Burdette, Ze Zhang Tang, Alan A. Arslan, Malcolm C. Pike, Sabina Sierri, J. Michael Gaziano, Lorna H. McNeil, Katherine A. McGlynn, Ulla Vogel, Logan G. Spector, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Jae Yong Park, Jennifer Prescott, Fernando Lecanda, Margaret A. Tucker, Ti Ding, Christian C. Abnet, Jenny Chang-Claude, Dimitrios Trichopoulos, Wei-Yen Lim, Wen Tan, Nick Orr, Jin Hee Kim, Stefano Porru, Chand Khanna, Robert R. McWilliams, Zhaoming Wang, Jeong Seon Ryu, David V. Conti, Alison P. Klein, Adonina Tardón, Robert J. Klein, Rebecca J. Rodabough, Mark H. Greene, Aruna Kamineni, Jie Lin, Rachael Z. Stolzenberg-Solomon, Patricia Hartge, Susan E. Hankinson, Young-Chul Kim, In Sam Kim, Luis Sierrasesúmaga, Roel Vermeulen, Paige M. Bracci, Mariana C. Stern, Louise A. Brinton, Myron D. Gross, Yong-Bing Xiang, Chih Yi Chen, G. A. Gerald Andriole, Paul S. Meltzer, Ying-Huang Tsai, Faith G. Davis, Ulrika Andersson, Paul Brennan, Sara Lindström, Chaoyu Wang, Giuseppe Mastrangelo, Laufey T. Amundadottir, Immaculata De Vivo, Bryan A. Bassig, Elisabete Weiderpass, Takashi Kohno, Nilanjan Chatterjee, Margaret R. Spitz, Pier Alberto Bertazzi, William Wheeler, David J. Hunter, Wei Tang, Qiuyin Cai, Naomi E. Allen, Molly Schwenn, Emily White, Min Shen, Adeline Seow, Laura E. Beane Freeman, James E. Mensah, Howard D. Sesso, Anna Luisa Di Stefano, Amanda Black, Manuela Gago-Dominguez, Christine B. Ambrosone, Avima M. Ruder, Martha S. Linet, Meir J. Stampfer, Robert C. Kurtz, Donald A. Barkauskas, Lisa W. Chu, Montserrat Garcia-Closas, Jason W. Hoskins, Melissa A. Austin, Kyoung Mu Lee, Jianxin Shi, Charles S. Fuchs, Nathaniel Rothman, Richard Gorlick, Piero Picci, Gianluca Severi, Ann G. Schwartz, Jian Gu, Christopher I. Amos, Marie-Christine Boutron-Ruault, Salvatore Panico, Alicja Wolk, Sara S. Strom, Lisa Mirabello, Jin-Hu Fan, Chin-Fu Hsiao, Neal D. Freedman, Geoffrey S. Tobias, Julie M. Gastier-Foster, Wang, Z, Zhu, B, Zhang, M, Parikh, H, Jia, J, Chung, Cc, Sampson, Jn, Hoskins, Jw, Hutchinson, A, Burdette, L, Ibrahim, A, Hautman, C, Raj, P, Abnet, Cc, Adjei, Aa, Ahlbom, A, Albanes, D, Allen, Ne, Ambrosone, Cb, Aldrich, M, Amiano, P, Amos, C, Andersson, U, Andriole G., Jr, Andrulis, Il, Arici, C, Arslan, Aa, Austin, Ma, Baris, D, Barkauskas, Da, Bassig, Ba, Beane Freeman, Le, Berg, Cd, Berndt, Si, Bertazzi, Pa, Biritwum, Rb, Black, A, Blot, W, Boeing, H, Boffetta, P, Bolton, K, Boutron Ruault, Mc, Bracci, Pm, Brennan, P, Brinton, La, Brotzman, M, Bueno de Mesquita, Hb, Buring, Je, Butler, Ma, Cai, Q, Cancel Tassin, G, Canzian, F, Cao, G, Caporaso, Ne, Carrato, A, Carreon, T, Carta, A, Chang, Gc, Chang, I, Chang Claude, J, Che, X, Chen, Cj, Chen, Cy, Chen, Ch, Chen, C, Chen, Ky, Chen, Ym, Chokkalingam, Ap, Chu, Lw, Clavel Chapelon, F, Colditz, Ga, Colt, J, Conti, D, Cook, Mb, Cortessis, Vk, Crawford, Ed, Cussenot, O, Davis, Fg, De Vivo, I, Deng, X, Ding, T, Dinney, Cp, Di Stefano, Al, Diver, Wr, Duell, Ej, Elena, Jw, Fan, Jh, Feigelson, H, Feychting, M, Figueroa, Jd, Flanagan, Am, Fraumeni JF, Jr, Freedman, Nd, Fridley, Bl, Fuchs, C, Gago Dominguez, M, Gallinger, S, Gao, Yt, Gapstur, Sm, Garcia Closas, M, Garcia Closas, R, Gastier Foster, Jm, Gaziano, Jm, Gerhard, D, Giffen, Ca, Giles, Gg, Gillanders, Em, Giovannucci, El, Goggins, M, Gokgoz, N, Goldstein, Am, Gonzalez, C, Gorlick, R, Greene, Mh, Gross, M, Grossman, Hb, Grubb R., 3rd, Gu, J, Guan, P, Haiman, Ca, Hallmans, G, Hankinson, Se, Harris, Cc, Hartge, P, Hattinger, C, Hayes, Rb, He, Q, Helman, L, Henderson, Be, Henriksson, R, Hoffman Bolton, J, Hohensee, C, Holly, Ea, Hong, Yc, Hoover, Rn, Hosgood HD, 3rd, Hsiao, Cf, Hsing, Aw, Hsiung, Ca, Hu, N, Hu, W, Hu, Z, Huang, M, Hunter, Dj, Inskip, Pd, Ito, H, Jacobs, Ej, Jacobs, Kb, Jenab, M, Ji, Bt, Johansen, C, Johansson, M, Johnson, A, Kaaks, R, Kamat, Am, Kamineni, A, Karagas, M, Khanna, C, Khaw, Kt, Kim, C, Kim, I, Kim, Yh, Kim, Yc, Kim, Yt, Kang, Ch, Jung, Yj, Kitahara, Cm, Klein, Ap, Klein, R, Kogevinas, M, Koh, Wp, Kohno, T, Kolonel, Ln, Kooperberg, C, Kratz, Cp, Krogh, V, Kunitoh, H, Kurtz, Rc, Kurucu, N, Lan, Q, Lathrop, M, Lau, Cc, Lecanda, F, Lee, Km, Lee, Mp, Le Marchand, L, Lerner, Sp, Li, D, Liao, Lm, Lim, Wy, Lin, D, Lin, J, Lindstrom, S, Linet, M, Lissowska, J, Liu, J, Ljungberg, B, Lloreta, J, Lu, D, Ma, J, Malats, N, Mannisto, S, Marina, N, Mastrangelo, G, Matsuo, K, Mcglynn, Ka, McKean Cowdin, R, Mcneill, Lh, Mcwilliams, Rr, Melin, B, Meltzer, P, Mensah, Je, Miao, X, Michaud, D, Mondul, Am, Moore, Le, Muir, K, Niwa, S, Olson, Sh, Orr, N, Panico, Salvatore, Park, Jy, Patel, Av, Patino Garcia, A, Pavanello, S, Peeters, Ph, Peplonska, B, Peters, U, Petersen, Gm, Picci, P, Pike, Mc, Porru, S, Prescott, J, Pu, X, Purdue, Mp, Qiao, Yl, Rajaraman, P, Riboli, E, Risch, Ha, Rodabough, Rj, Rothman, N, Ruder, Am, Ryu, J, Sanson, M, Schned, A, Schumacher, Fr, Schwartz, Ag, Schwartz, Kl, Schwenn, M, Scotlandi, K, Seow, A, Serra, C, Serra, M, Sesso, Hd, Severi, G, Shen, H, Shen, M, Shete, S, Shiraishi, K, Shu, Xo, Siddiq, A, Sierrasesumaga, L, Sierri, S, Loon Sihoe, Ad, Silverman, Dt, Simon, M, Southey, Mc, Spector, L, Spitz, M, Stampfer, M, Stattin, P, Stern, Mc, Stevens, Vl, Stolzenberg Solomon, Rz, Stram, Do, Strom, S, Su, Wc, Sund, M, Sung, Sw, Swerdlow, A, Tan, W, Tanaka, H, Tang, W, Tang, Zz, Tardon, A, Tay, E, Taylor, Pr, Tettey, Y, Thomas, Dm, Tirabosco, R, Tjonneland, A, Tobias, G, Toro, Jr, Travis, Rc, Trichopoulos, D, Troisi, R, Truelove, A, Tsai, Yh, Tucker, Ma, Tumino, R, Van Den Berg, D, Van Den Eeden, Sk, Vermeulen, R, Vineis, P, Visvanathan, K, Vogel, U, Wang, C, Wang, J, Wang, S, Weiderpass, E, Weinstein, Sj, Wentzensen, N, Wheeler, W, White, E, Wiencke, Jk, Wolk, A, Wolpin, Bm, Wong, Mp, Wrensch, M, Wu, C, Wu, T, Wu, X, Wu, Yl, Wunder, J, Xiang, Yb, Xu, J, Yang, Hp, Yang, Pc, Yatabe, Y, Ye, Y, Yeboah, Ed, Yin, Z, Ying, C, Yu, Cj, Yu, K, Yuan, Jm, Zanetti, Ka, Zeleniuch Jacquotte, A, Zheng, W, Zhou, B, Mirabello, L, Savage, Sa, Kraft, P, Chanock, Sj, Yeager, M, Landi, Mt, Shi, J, Chatterjee, N, Amundadottir, Lt, Wang, Z., Zhu, B., Zhang, M., Parikh, H., Jia, J., Chung, C.C., Sampson, J.N., Hoskins, J.W., Hutchinson, A., Burdette, L., Ibrahim, A., Hautman, C., Raj, P.S., Abnet, C.C., Adjei, A.A., Ahlbom, A., Albanes, D., Allen, N.E., Ambrosone, C.B., Aldrich, M., Amiano, P., Amos, C., Andersson, U., Gerald Andriole, G.A., Jr., Andrulis, I.L., Arici, C., Arslan, A.A., Austin, M.A., Baris, D., Barkauskas, D.A., Bassig, B.A., Freeman, L.E.B., Berg, C.D., Berndt, S.I., Bertazzi, P.A., Biritwum, R.B., Black, A., Blot, W., Boeing, H., Boffetta, P., Bolton, K., Boutron-Ruault, M.-C., Bracci, P.M., Brennan, P., Brinton, L.A., Brotzman, M., Bueno-de-Mesquita, H.B., Buring, J.E., Butler, M.A., Cai, Q., Cancel-Tassin, G., Canzian, F., Cao, G., Caporaso, N.E., Carrato, A., Carreon, T., Carta, A., Chang, G.-C., Chang, I.-S., Chang-Claude, J., Che, X., Chen, C.-J., Chen, C.-Y., Chen, C.-H., Chen, C., Chen, K.-Y., Chen, Y.-M., Chokkalingam, A.P., Chu, L.W., Clavel-Chapelon, F., Colditz, G.A., Colt, J.S., Conti, D., Cook, M.B., Cortessis, V.K., Crawford, E.D., Cussenot, O., Davis, F.G., De Vivo, I., Deng, X., Ding, T., Dinney, C.P., Di Stefano, A.L., Diver, W.R., Duell, E.J., Elena, J.W., Fan, J.-H., Feigelson, H.S., Feychting, M., Figueroa, J.D., Flanagan, A.M., Fraumeni, J.F., Jr., Freedman, N.D., Fridley, B.L., Fuchs, C.S., Gago-Dominguez, M., Gallinger, S., Gao, Y.-T., Gapstur, S.M., Garcia-Closas, M., Garcia-Closas, R., Gastier-Foster, J.M., Gaziano, J.M., Gerhard, D.S., Giffen, C.A., Giles, G.G., Gillanders, E.M., Giovannucci, E.L., Goggins, M., Gokgoz, N., Goldstein, A.M., Gonzalez, C., Gorlick, R., Greene, M.H., Gross, M., Grossman, H.B., Grubb, R., III and Gu, J., Guan, P., Haiman, C.A., Hallmans, G., Hankinson, S.E., Harris, C.C., Hartge, P., Hattinger, C., Hayes, R.B., He, Q., Helman, L., Henderson, B.E., Henriksson, R., Hoffman-Bolton, J., Hohensee, C., Holly, E.A., Hong, Y.-C., Hoover, R.N., Dean Hosgood, H., Hsiao, C.-F., Hsing, A.W., Hsiung, C.A., Hu, N., Hu, W., Hu, Z., Huang, M.-S., Hunter, D.J., Inskip, P.D., Ito, H., Jacobs, E.J., Jacobs, K.B., Jenab, M., Ji, B.-T., Johansen, C., Johansson, M., Johnson, A., Kaaks, R., Kamat, A.M., Kamineni, A., Karagas, M., Khanna, C., Khaw, K.-T., Kim, C., Kim, I.-S., Kim, J.H., Kim, Y.H., Kim, Y.-C., Kim, Y.T., Kang, C.H., Jung, Y.J., Kitahara, C.M., Klein, A.P., Klein, R., Kogevinas, M., Koh, W.-P., Kohno, T., Kolonel, L.N., Kooperberg, C., Kratz, C.P., Krogh, V., Kunitoh, H., Kurtz, R.C., Kurucu, N., Lan, Q., Lathrop, M., Lau, C.C., Lecanda, F., Lee, K.-M., Lee, M.P., Marchand, L.L., Lerner, S.P., Li, D., Liao, L.M., Lim, W.-Y., Lin, D., Lin, J., Lindstrom, S., Linet, M.S., Lissowska, J., Liu, J., Ljungberg, B., Lloreta, J., Lu, D., Ma, J., Malats, N., Mannisto, S., Marina, N., Mastrangelo, G., Matsuo, K., McGlynn, K.A., McKean-Cowdin, R., McNeil, L.H., McWilliams, R.R., Melin, B.S., Meltzer, P.S., Mensah, J.E., Miao, X., Michaud, D.S., Mondul, A.M., Moore, L.E., Muir, K., Niwa, S., Olson, S.H., Orr, N., Panico, S., Park, J.Y., Patel, A.V., Patino-Garcia, A., Pavanello, S., Peeters, P.H.M., Peplonska, B., Peters, U., Petersen, G.M., Picci, P., Pike, M.C., Porru, S., Prescott, J., Pu, X., Purdue, M.P., Qiao, Y.-L., Rajaraman, P., Riboli, E., Risch, H.A., Rodabough, R.J., Rothman, N., Ruder, A.M., Ryu, J.-S., Sanson, M., Schned, A., Schumacher, F.R., Schwartz, A.G., Schwartz, K.L., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H.D., Severi, G., Shen, H., Shen, M., Shete, S., Shiraishi, K., Shu, X.-O., Siddiq, A., Sierrasesumaga, L., Sierri, S., Sihoe, A.D.L., Silverman, D.T., Simon, M., Southey, M.C., Spector, L., Spitz, M., Stampfer, M., Stattin, P., Stern, M.C., Stevens, V.L., Stolzenberg-Solomon, R.Z., Stram, D.O., Strom, S.S., Su, W.-C., Sund, M., Sung, S.W., Swerdlow, A., Tan, W., Tanaka, H., Tang, W., Tang, Z.-Z., Tardon, A., Tay, E., Taylor, P.R., Tettey, Y., Thomas, D.M., Tirabosco, R., Tjonneland, A., Tobias, G.S., Toro, J.R., Travis, R.C., Trichopoulos, D., Troisi, R., Truelove, A., Tsai, Y.-H., Tucker, M.A., Tumino, R., Van Den Berg, D., Van Den Eeden, S.K., Vermeulen, R., Vineis, P., Visvanathan, K., Vogel, U., Wang, C., Wang, J., Wang, S.S., Weiderpass, E., Weinstein, S.J., Wentzensen, N., Wheeler, W., White, E., Wiencke, J.K., Wolk, A., Wolpin, B.M., Wong, M.P., Wrensch, M., Wu, C., Wu, T., Wu, X., Wu, Y.-L., Wunder, J.S., Xiang, Y.-B., Xu, J., Yang, H.P., Yang, P.-C., Yatabe, Y., Ye, Y., Yeboah, E.D., Yin, Z., Ying, C., Yu, C.-J., Yu, K., Yuan, J.-M., Zanetti, K.A., Zeleniuch-Jacquotte, A., Zheng, W., Zhou, B., Mirabello, L., Savage, S.A., Kraft, P., Chanock, S.J., Yeager, M., Landi, M.T., Shi, J., Chatterjee, N., and Amundadottir, L.T.

Subjects
Male, SINGLE-NUCLEOTIDE POLYMORPHISM, Genome-wide association study, Epigenesis, Genetic, Gene Frequency, Molecular Biology, Genetics, Genetics (clinical), Neoplasms, Odds Ratio, Genome-wide association studies (GWAS), Telomerase, DNA METHYLATION Author Information, Association Studies Articles, General Medicine, PANCREATIC-CANCER, PROSTATE-CANCER, Neoplasm Proteins, POSTMENOPAUSAL BREAST-CANCER, TERT PROMOTER MUTATIONS, Gene Expression Regulation, Neoplastic, 2 SUSCEPTIBILITY LOCI, DNA methylation, Chromosomes, Human, Pair 5, Female, Risk, Locus (genetics), Single-nucleotide polymorphism, TERT and CLPTM1L gene, Biology, Polymorphism, Single Nucleotide, LUNG-CANCER, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Allele, Gene, Allele frequency, Alleles, Genetic association, chromosome 5p15.33, Computational Biology, Membrane Proteins, DNA Methylation, Genetic Loci, TELOMERE LENGTH, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

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