[Show abstract][Hide abstract] ABSTRACT: Low income, high-tuberculosis burden, countries are considering selective deployment of Xpert MTB/RIF assay (Xpert) due to high cost per test. We compared the diagnostic gain of the Xpert add-on strategy with Xpert replacement strategy for pulmonary tuberculosis diagnosis among HIV-infected adults to inform its implementation.
[Show abstract][Hide abstract] ABSTRACT: Minimal invasive but accurate methods to establish the cause of death in HIV-infected patients are needed. We studied the agreement in cause of death between blind and ultrasound-guided needle autopsy and complete autopsy in HIV-infected patients in Uganda.
Journal of acquired immune deficiency syndromes (1999). 07/2014;
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.
We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole.
The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P=0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P=0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P=0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P=0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups.
Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.).
New England Journal of Medicine 06/2014; 370(26):2487-98. · 54.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Testosterone, a male reproductive hormone, affects several physiological processes, such as sperm production, energy, strength, sexual behavior, sleep and the general well being of men. Normal levels of testosterone are necessary to effect these physiological processes. The objective of this study was to study the association between testosterone levels in a sample of Ugandan men with socio-demographic characteristics, and compare the testosterone levels of Ugandan men with that of men in other countries.
African Health Sciences 06/2014; 14(2):348-55. · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rationale:Smear microscopy has suboptimal sensitivity, and there is a need to improve its performance since it is commonly used to diagnose tuberculosis (TB).Objectives:We prospectively evaluated the diagnostic accuracy of the Small Membrane Filtration (SMF) method, an approach that uses a vacuum manifold and is designed to concentrate bacilli onto a filter that can be examined microscopically.Methods:We enrolled hospitalized adult pulmonary TB suspects in Kampala, Uganda. We obtained a clinical history and three spontaneously expectorated sputum specimens for smear microscopy (direct, concentrated and SMF), MGIT 960 and Lowenstein Jensen (LJ) cultures, and Xpert MRB/RIF testing. We performed per-specimen (primary) and per-patient analyses.Results:From October 2012 to June 2013 we enrolled 212 patients (579 sputum specimens). Participants were mostly female (63.2%); 81.6% were HIV-infected, with median CD4 47 cells/μL. Overall, 19.0%, 20.4%, 27.1%, 25.2% and 25.9% of specimens tested positive by direct smear, concentrated smear, MGIT, LJ and Xpert, respectively. In the per-specimen analysis, the sensitivity of the SMF method (48.5%, 95% CI 37.4% - 59.6%) was lower than that of direct smear (60.9%, 51.4% - 70.5%, p=0.0001) and concentrated smear (63.3%, 53.6% - 73.1%, p<0.0001). Sub-group analyses showed that SMF performed poorly in specimens having low volume or low bacterial load.Conclusions:The SMF method performed poorly compared to standard smear techniques, and was sensitive to sample preparation techniques. The optimal laboratory SMF protocol may require striking a fine balance between sample dilution and filtration failure rate.
Journal of clinical microbiology 05/2014; · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cataracts contribute 12% of visual loss among HIV-infected adults in Uganda. Immuno-pathogenesis of cataracts may differ among HIV-infected individuals; thus the need for innovative therapeutic interventions among HIV-infected adults.
In a laboratory based case-control study, nested in a clinical/surgical community outreach camp, 50 adults with cataracts eligible for surgery were selected consecutively. HIV testing was done for individuals with unknown HIV sero-status. Peripheral Blood Mononuclear Cells (PBMC) were collected from all HIV-positive-adults-with-cataracts (cases) and HIV-negative-adults-with-cataracts (comparative group) and age-matched HIV-negative and HIV-positive- adults- without-cataracts (comparative group). Treg were measured as CD3+CD4+FoxP3+CD25+(bright) and immune activation as CD3+CD4+CD38+HALDR+ using a Facs Canto II flowcytometer. Mann Whitney test was used to compare expression among the four groups.
Of 50 adults operated for cataracts, 24 (48%) were female, 25(50%) were HIV-positive. HIV-positive-individuals had cataracts earlier [median; Inter-quartile Range (IQR); 49(44-53) years] than HIV-negative [70 (IQR 59-75) years]; p=0.0005.Treg were lower among individuals with cataracts irrespective of HIV status; p=0.001; but comparable among younger HIV-positive and elderly HIV-negative with cataracts; p=0.301. Immune activation levels were comparable among HIV-positive and HIV-negative individuals with cataracts. However, HIV-positive-individuals with cataracts expressed higher levels of immune activation than HIV-positive-individuals without cataracts; p=0.012 and HIV-negative-individuals-with-cataracts expressed higher levels of immune activation that HIV-negative-without-cataracts; p<0.0001.
CD4 T-cell activation and reduced regulatory T-cell populations were associated with cataracts among adults aging with HIV. We recommend studies on clinical relevance of immune modulation in the prevention of early development of cataracts among adults aging with HIV in Africa.
[Show abstract][Hide abstract] ABSTRACT: In settings of high HIV prevalence, tuberculosis control and patient management are hindered by lack of accurate, rapid tuberculosis diagnostic tests that can be performed at point-of-care. The Determine TB LAM Ag ('TB LAM') test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis.
Prospective diagnostic accuracy study.
Hospital and outpatient settings in Uganda and South Africa.
HIV-infected adults with tuberculosis symptoms and/or signs.
Participants provided a fresh urine specimen for TB LAM testing, blood for mycobacterial culture, and two respiratory specimens for smear microscopy and mycobacterial culture.
For the TB LAM test, sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis.
1013 participants were enrolled. Among culture-positive tuberculosis patients, the TB LAM test identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4≤100 cells/mm. The test was specific in 559/573 (97.6%) of patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with CD4≤100. CD4≤50 (adjusted odds ratio [AOR] 6.2, P<0.001) or 51-100 (AOR 7.1, P<0.001), mycobacteremia (AOR 6.1; P<0.01) and hospitalization (AOR 2.6, P=0.03) were independently associated with a positive TB LAM test.
In HIV-positive adults with CD4≤100, the TB LAM urine test detected over half of culture-positive tuberculosis patients, in less than 30 minutes and without the need for equipment or reagents.
[Show abstract][Hide abstract] ABSTRACT: Xpert MTB/RIF ('Xpert') and urinary lipoarabinomannan (LAM) assays offer rapid tuberculosis (TB) diagnosis, but have suboptimal sensitivity when used individually in HIV-positive patients. The yield of these tests used in combination for the diagnosis of active TB among HIV-infected TB suspects is unknown.
Study of comparative diagnostic accuracy nested into a prospective study of HIV-infected individuals with signs and/or symptoms of TB in Uganda.
Xpert testing of archived sputum was conducted for culture-confirmed TB cases and TB suspects in whom a diagnosis of TB was excluded. Additional testing included sputum smear microscopy, sputum culture (solid and liquid media), mycobacterial blood culture, and urinary testing for LAM using a lateral flow test ('LF-LAM') and an enzyme-linked immunosorbance assay ('ELISA-LAM').
Among 103 participants with culture-confirmed TB, sensitivity of Xpert was 76% (95% confidence interval, CI 0.66-0.84), and was superior to that of LF-LAM (49%, 95% CI 0.39-0.59, P < 0.001). Specificity was greater than 97% for both tests among 105 individuals without TB. The combination of smear microscopy and LF-LAM identified 67% (95% CI 0.57-0.76) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone (P = 0.15). The sensitivity of the combination of Xpert and LF-LAM was 85% (88/103 95% CI 0.77-0.92), which was superior to either test alone (P < 0.05) and approached sensitivity of sputum liquid culture testing (94%, 95% CI 0.88-0.98, P = 0.17).
Sputum Xpert and urinary LAM assays were complementary for the diagnosis of active TB in HIV-infected patients, and sensitivity of the combination of these tests was superior to that of either test alone.
AIDS (London, England) 03/2014; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infertility is a public health problem associated with devastating psychosocial consequences. In countries where infertility care is difficult to access, women turn to herbal medicines to achieve parenthood. The aim of this study was to determine the prevalence and factors associated with herbal medicine use by women attending the infertility clinic.
This was a cross-sectional study of 260 women attending the infertility clinic at Mulago hospital. The interviewer administered questionnaire comprised socio-demographic characteristics, infertility-related aspects and information on herbal medicine use. The main outcome measure was herbal medicines use for infertility treatment. Determinants of herbal medicine use were assessed using multivariable logistic regression.
The majority (76.2%) of respondents had used herbal medicines for infertility treatment. The mean age of the participants was 28.3 years +/- 5.5. Over 80% were married, 59.6% had secondary infertility and 2/3 of the married participants were in monogamous unions. In a multivariable model, the variables that were independently associated with increased use of herbal medicine among infertile patients were being married (OR 2.55, CI 1.24-5.24), never conceived (OR 4.08 CI 1.86-8.96) and infertility for less than 3 years (OR 3.52 CI 1.51-8.821). Factors that were associated with less use of herbal medicine among infertile women were being aged 30 years or less (OR 0.18 CI 0.07-0.46), primary and no education (OR 0.12 CI 0.05-0.46) and living with partner for less than three years (OR 0.39 CI 0.16-0.93).
The prevalence of herbal medicine use among women attending the infertility clinic was 76.2%. Herbal medicine use was associated with the participants' age, level of education, marital status, infertility duration, nulliparity, and duration of marriage. Medical care was often delayed and the majority of the participants did not disclose use of herbal medicines to the attending physician. Health professionals should enquire about use of herbal medicines. This may help in educating the patients about the health risks of using herbal medicine and may reduce delays in seeking appropriate care. Collaboration of health professionals with herbal medicine practitioners would help identify the common herbal medicines used for infertility treatment, their potential benefits and harm.
BMC Complementary and Alternative Medicine 01/2014; 14(1):27. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Informed consent is premised on the participants' understanding the scope of the research and the associated risks and benefits. The objective was to evaluate the improvement in knowledge in a population unfamiliar with clinical trial concepts about "what it means to be part of a clinical trial" using an innovative educational tool called the 'Speaking Book'.
This was a randomized controlled trial conducted at a research site in Uganda. 201 participants were randomized to: 1) clinical trials information session control arm, or 2) clinical trials information session followed by instruction in the use of the Speaking Book with a take-home copy (intervention arm). After the session, participants of both groups completed a 22-item multiple-choice test on the rights and responsibilities of participants. Participants returned after one week to complete the same test to assess knowledge retention. The mean pre- and post-test score difference was assessed according to trial arm using an unpaired t-test of proportions.
Ninety-one (90%) participants completed both the initial and follow-up tests in the control arm and 100 (100%) in the intervention arm. The average age of participants was 38 years, 53% were female and 67% were employed; 20% had previously been invited to participate in a clinical trial; of these, 19% had participated. The mean difference in proportion of correct responses from test 1 to test 2 was 2.7% (95%CI 0.3%-5.0%) for the control arm and 11.6% (95%CI 9.3%-13.7%) for the intervention arm (t-score= -5.3, p-value<0.0001).
Participants who had instruction in the use of the Speaking Book had a larger increase in knowledge than those who had no access to this tool. To better engage patients unfamiliar with clinical trial concepts, innovative educational techniques can assist to increase knowledge to make an informed decision about participation in a clinical trial.
Journal of clinical research & bioethics. 01/2014; 5:165.
[Show abstract][Hide abstract] ABSTRACT: Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB) and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA) result for urine lipoarabinomannan (LAM) and cryptococcal antigenuria was associated with mortality.
PLoS ONE 01/2014; 9(7):e101459. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract
Xpert MTB/RIF (‘Xpert’) and urinary lateral-flow lipoarabinomannan (LF-LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert and LF-LAM for the detection of active TB among people living with HIV.
Cost-effectiveness analysis using data from a comparative study of LF-LAM and Xpert, with a target population of HIV-infected individuals with signs/symptoms of TB in Uganda.
A decision-analysis model compared multiple strategies for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the costs and DALY's averted for each algorithm. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER).
Compared with an algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear-microscopy was a less effective strategy than Xpert replacement of smear-microscopy, but was less costly and also considered highly cost-effective (ICER $33 per DALY-averted) compared with continued usage of smear-microscopy alone. Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by HIV/ART costs and life-expectancy of patients after TB treatment.
The addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected individuals is highly cost-effective compared with usage of either sputum smear-microscopy or Xpert alone.
AIDS 11/2013; 27(18):2883-2892. · 6.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs) averted.
The decision analytic model reflected the perspective of the national health care system and was based on the sensitivity (86%) and specificity (99%) reported for the immunochromatographic strip (ICS) test. Clinical outcomes of infants born to syphilis-infected mothers on the end points of stillbirth, neonatal death, and congenital syphilis were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin. Country-specific inputs included the antenatal prevalence of syphilis, annual number of live births, proportion of women with at least one antenatal care visit, per capita gross national income, and estimated hourly nurse wages. In all 43 sub-Saharan African countries analyzed, syphilis screening is highly cost-effective, with an average cost/DALY averted of US$11 (range: US$2-US$48). Screening remains highly cost-effective even if the average prevalence falls from the current rate of 3.1% (range: 0.6%-14.0%) to 0.038% (range: 0.002%-0.113%). Universal antenatal screening of pregnant women in clinics may reduce the annual number of stillbirths by up to 64,000, neonatal deaths by up to 25,000, and annual incidence of congenital syphilis by up to 32,000, and avert up to 2.6 million DALYs at an estimated annual direct medical cost of US$20.8 million.
Use of ICS tests for antenatal syphilis screening is highly cost-effective in SSA. Substantial reduction in DALYs can be achieved at a relatively modest budget impact. In SSA, antenatal programs should expand access to syphilis screening using the ICS test. Please see later in the article for the Editors' Summary.
PLoS Medicine 11/2013; 10(11):e1001545. · 15.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In-patient hospitals in South Africa and Uganda.
To evaluate the cost-effectiveness of a lateral-flow urine lipoarabinomannan (LAM) test when added to existing strategies for tuberculosis (TB) diagnosis in human immunodeficiency virus infected adults (CD4(+) T-cell counts < 100 cells/l) with symptoms of active TB.
Decision-analytic cost-utility model, with the primary outcome being the incremental cost-effectiveness ratio, expressed in 2010 US dollars per disability-adjusted life year (DALY) averted from the perspective of a public sector TB control program.
For every 1000 patients tested, adding lateral-flow urine LAM generated 80 incremental appropriate anti-tuberculosis treatments and averted 224 DALYs. Estimated cost utility was US$353 per DALY averted (95% uncertainty range $192$1161) in South Africa and $86 per DALY averted (95% uncertainty range $49$239) in Uganda, reflecting the lower treatment costs in Uganda. Cost utility was most sensitive to assay specificity, cost of anti-tuberculosis treatment, life expectancy after TB cure and cohort TB prevalence, but did not rise above $1500 per DALY averted in South Africa under any one-way sensitivity analysis. The probability of acceptability was >99.8% at a per-DALY willingness-to-pay threshold equal to the per capita gross domestic product in South Africa ($7275) and Uganda ($509).
The International Journal of Tuberculosis and Lung Disease 04/2013; 17(4):552-8. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A human immunodeficiency virus (HIV) clinic in a setting of high tuberculosis (TB) and HIV prevalence.
To study the incidence of and factors associated with tuberculin skin test (TST) conversion in HIV patients on antiretroviral therapy (ART).
Prospective cohort study of TST-negative, ART-naïve HIV patients (CD4 cell count < 250 cells/l) without active TB. TST was repeated at 2 months and, if negative, at 6 months. TST positivity was defined as an induration of ≥5 mm. Clinical examination, chest X-ray and CD4 cell counts were performed at baseline and follow-up. Proportions and incidence of TST conversion were calculated, and logistic regression analyses were performed.
Of the 142 patients, 105 (75.5%) were females. The mean age was 35.9 years (standard deviation 8.1) and the median CD4 cell count was 119 cells/l (interquartile range 42168). The incidence of TST conversion was 30.2/100 person years (95%CI 19.546.8). Conversion was not associated with clinical, CD4 cell count or chest radiography findings.
A high incidence of TST conversion was observed, supporting the World Health Organization recommendation to provide isoniazid preventive therapy (IPT) to all HIV patients in high TB prevalence settings. If case-control programmes choose to provide IPT only to TST-positive patients, repeat TST should be considered following initiation of ART.
The International Journal of Tuberculosis and Lung Disease 03/2013; 17(3):336-41. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: There is a high incidence of tuberculosis (TB) early after antiretroviral treatment (ART) initiation. This historical cohort study evaluated the association of efavirenz (EFV) compared to nevirapine (NVP) with post-ART TB among patients initiated on first-line ART from 2005 to 2009 in a large, urban HIV clinic in Uganda. METHODS: Hazard ratios (HR) for developing TB were computed using multivariable Cox proportional hazards models with inverse weighting of the probability of being prescribed NVP or EFV (calculated by a multivariable logistic regression model), stratifying by baseline CD4 count. Adjustment for time-updated CD4 count, restriction of the analysis to patients remaining in follow-up and a TB free survival analysis were performed as sensitivity analyses. RESULTS: ART was initiated in 5797 patients; 66% were women with a mean age of 37 years (standard deviation, 9 years) and a median baseline CD4 count of 117 cells/mm(3) (interquartile range, 43, 182). Sixty percent (n=3484) were initiated on NVP and 40% (n=2313) on EFV. In the first 2 years of ART, 377 patients developed TB. The use of EFV compared to NVP was independently associated with higher TB incidence in patients with a baseline CD4 count <100 cells/mm(3) (HR 2.05 [95% CI 1.29-3.27], P=0.003), but not at higher CD4 counts (HR 0.71 [95% CI 0.39-1.31], P=0.428). These estimates were robust to all sensitivity analyses. CONCLUSIONS: There was a higher incidence of TB in patients with baseline CD4 counts <100 cells/mm(3) initiated on EFV compared to those initiated on NVP. Further research in a trial setting or a larger multi-site observational cohort is needed to confirm these findings.
[Show abstract][Hide abstract] ABSTRACT: There is conflicting data on long-term CD4 immune recovery after combination antiretroviral therapy (ART) in resource-limited settings. Virologic suppression is rarely documented in cohorts from sub-Saharan Africa so objective evidence of adherence is biologically unsubstantiated. We sought to investigate long-term patterns of immune recovery in Ugandan patients on ART with sustained viral suppression.
A prospective cohort of patients starting ART between April, 2004 and April, 2005 at the Infectious Diseases Institute with sustained viral suppression (viral load ≤400 copies/ml at month 6 and 12) while on first-line ART. Propensity scores were used to adjust for treatment allocation (nevirapine or efavirenz) at ART initiation. Data were analyzed using Kaplan Meier methods and cross-sectional time series regression.
Three hundred and fifty-six patients were included in the analysis.71.6% were female, 87% in WHO stage 3 or 4, median age was 37 years, (IQR:32-43), and median CD4 count was 108 cells/µL, (IQR:35-174) at ART start. At multivariable analysis, lower immune recovery (measured by change in CD4 from ART start at each time interval) was associated with male-gender (-59, 95% CI: 90, -28, P<0.001), baseline CD4 count of 101-200 cells/µL (-35, 95% CI: 62, -9, P=0.009) and >200 (-64, 95% CI: 101, -26, P=0.001), and use of AZT at baseline (-47, 95% CI: -74, -20, P=0.001). Median time to reach >400 cells/µL was longer in males (197.4 weeks, IQR:119.9-312.0), compared to females (144.7 weeks, IQR:96.6-219.7, P<0.001). The cumulative probability of attaining CD4 >400 cells/µL over 7 years was higher in females compared to males (P<0.001).
There was long-term, continuous, immunologic recovery up to 7 years after ART initiation in an urban Ugandan cohort. Virologically suppressed women had better sustained immune recovery than men. Men take longer to immune reconstitute and have a lower probability of reaching a CD4 cell count >400 cells/µL. The biologic mechanisms of these gender differences need further exploration.
PLoS ONE 01/2013; 8(8):e73190. · 3.53 Impact Factor