Publications by authors named "Sara Jenks"

12 Publications

  • Page 1 of 1

Diagnostic performance of the combined nasal and throat swab in patients admitted to hospital with suspected COVID-19.

BMC Infect Dis 2021 Apr 6;21(1):318. Epub 2021 Apr 6.

BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4SA, UK.

Background: Accurate diagnosis in patients with suspected coronavirus disease 2019 (COVID-19) is essential to guide treatment and limit spread of the virus. The combined nasal and throat swab is used widely, but its diagnostic performance is uncertain.

Methods: In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, we evaluated the combined nasal and throat swab with reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in consecutive patients admitted to hospital with suspected COVID-19. Diagnostic performance of the index and serial tests was evaluated for a primary outcome of confirmed or probable COVID-19, and a secondary outcome of confirmed COVID-19 on serial testing. The diagnosis was adjudicated by a panel, who recorded clinical, laboratory and radiological features blinded to the test results.

Results: We enrolled 1368 consecutive patients (median age 68 [interquartile range, IQR 53-80] years, 47% women) who underwent a total of 3822 tests (median 2 [IQR 1-3] tests per patient). The primary outcome occurred in 36% (496/1368), of whom 65% (323/496) and 35% (173/496) had confirmed and probable COVID-19, respectively. The index test was positive in 255/496 (51%) patients with the primary outcome, giving a sensitivity and specificity of 51.4% (95% confidence interval [CI] 48.8 to 54.1%) and 99.5% (95% CI 99.0 to 99.8%). Sensitivity increased in those undergoing 2, 3 or 4 tests to 60.1% (95% CI 56.7 to 63.4%), 68.3% (95% CI 64.0 to 72.3%) and 77.6% (95% CI 72.7 to 81.9%), respectively. The sensitivity of the index test was 78.9% (95% CI 74.4 to 83.2%) for the secondary outcome of confirmed COVID-19 on serial testing.

Conclusions: In patients admitted to hospital, a single combined nasal and throat swab with RT-PCR for SARS-CoV-2 has excellent specificity, but limited diagnostic sensitivity for COVID-19. Diagnostic performance is significantly improved by repeated testing.
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http://dx.doi.org/10.1186/s12879-021-05976-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022129PMC
April 2021

Absence of SARS-CoV-2 neutralizing activity in pre-pandemic sera from individuals with recent seasonal coronavirus infection.

Clin Infect Dis 2020 Dec 3. Epub 2020 Dec 3.

Laboratory of Retrovirology, The Rockefeller University, New York NY.

Cross-reactive immune responses elicited by seasonal coronaviruses might impact SARS-CoV-2 susceptibility and disease outcomes. We measured neutralizing activity against SARS-CoV-2 in pre-pandemic sera from patients with prior PCR-confirmed seasonal coronavirus infection. While neutralizing activity against seasonal coronaviruses was detected in nearly all sera, cross-reactive neutralizing activity against SARS-CoV-2 was undetectable.
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http://dx.doi.org/10.1093/cid/ciaa1803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799301PMC
December 2020

Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients.

J Infect Dis 2021 02;223(3):389-398

Laboratory of Retrovirology, The Rockefeller University, New York, New York, USA.

Background: Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity.

Methods: We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens.

Results: Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81-100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3-4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers.

Conclusions: Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection.
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http://dx.doi.org/10.1093/infdis/jiaa659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665595PMC
February 2021

Absence of SARS-CoV-2 neutralizing activity in pre-pandemic sera from individuals with recent seasonal coronavirus infection.

medRxiv 2020 Oct 11. Epub 2020 Oct 11.

Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065.

Cross-reactive immune responses elicited by seasonal coronaviruses might impact SARS-CoV-2 susceptibility and disease outcomes. We measured neutralizing activity against SARS-CoV-2 in pre-pandemic sera from patients with prior PCR-confirmed seasonal coronavirus infection. While neutralizing activity against seasonal coronaviruses was detected in nearly all sera, cross-reactive neutralizing activity against SARS-CoV-2 was undetectable.
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http://dx.doi.org/10.1101/2020.10.08.20209650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553167PMC
October 2020

Longitudinal analysis of clinical serology assay performance and neutralising antibody levels in COVID19 convalescents.

medRxiv 2020 Aug 6. Epub 2020 Aug 6.

Royal Infirmary of Edinburgh, NHS Lothian, 51 Little France Crescent, Edinburgh EH16 4SA.

Objectives: To investigate longitudinal trajectory of SARS-CoV-2 neutralising antibodies and the performance of serological assays in diagnosing prior infection and predicting serum neutralisation titres with time Design Retrospective longitudinal analysis of a COVID19 case cohort . Setting NHS outpatient clinics Participants Individuals with RT-PCR diagnosed SARS-CoV-2 infection that did not require hospitalization Main outcome measures The sensitivity with which prior infection was detected and quantitative antibody titres were assessed using four SARS-CoV-2 serologic assay platforms. Two platforms employed SARS-CoV-2 spike (S) based antigens and two employed nucleocapsid (N) based antigens. Serum neutralising antibody titres were measured using a validated pseudotyped virus SARS-CoV-2 neutralisation assay. The ability of the serological assays to predict neutralisation titres at various times after PCR diagnosis was assessed. Results The three of the four serological assays had sensitivities of 95 to100% at 21-40 days post PCR-diagnosis, while a fourth assay had a lower sensitivity of 85%. The relative sensitivities of the assays changed with time and the sensitivity of one assay that had an initial sensitivity of >95% declined to 85% at 61-80 post PCR diagnosis, and to 71% at 81-100 days post diagnosis. Median antibody titres decreased in one serologic assay but were maintained over the observation period in other assays. The trajectories of median antibody titres measured in serologic assays over this time period were not dependent on whether the SARS-CoV-2 N or S proteins were used as antigen source. A broad range of SARS-CoV-2 neutralising titres were evident in individual sera, that decreased over time in the majority of participants; the median neutralisation titre in the cohort decreased by 45% over 4 weeks. Each of the serological assays gave quantitative measurements of antibody titres that correlated with SARS-CoV-2 neutralisation titres, but, the S-based serological assay measurements better predicted serum neutralisation potency. The strength of correlation between serologic assay results and neutralisation titres deteriorated with time and decreases in neutralisation titres in individual participants were not well predicted by changes in antibody titres measured using serologic assays.

Conclusions: SARS-CoV-2 serologic assays differed in their comparative diagnostic performance over time. Different assays are more or less well suited for surveillance of populations for prior infection versus prediction of serum neutralisation potency. Continued monitoring of declining neutralisation titres during extended follow up should facilitate the establishment of appropriate serologic correlates of protection against SARS-CoV-2 reinfection.
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http://dx.doi.org/10.1101/2020.08.05.20169128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418752PMC
August 2020

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes.

Diabetologia 2017 08 20;60(8):1400-1408. Epub 2017 May 20.

Centre for Population Health Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh, EH8 9AG, UK.

Aims/hypothesis: We investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes.

Methods: A cohort of 1066 Scottish men and women aged 60-74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml min (1.73 m) at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models.

Results: A total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286).

Conclusions/interpretation: Our findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention.
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http://dx.doi.org/10.1007/s00125-017-4297-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491560PMC
August 2017

A Snapshot of Urban Adolescent Women's Contraceptive Knowledge at the Onset of a Community Long-Acting Reversible Contraceptive Promotion Initiative.

J Pediatr Adolesc Gynecol 2017 Aug 12;30(4):474-478. Epub 2017 Jan 12.

Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York; Hoekelman Center, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York.

Study Objective: To contextualize young women's knowledge and attitudes regarding contraception at the outset of an intervention promoting long-acting reversible contraceptive (LARC) use for teen pregnancy prevention.

Design And Setting: Our intervention was on the basis of diffusion of innovation theory, and at the outset we were interested in likely early adopters' existing knowledge and attitudes toward contraception. This mixed methods study consisted of focus groups within positive youth development programs in Rochester, New York; we discussed young women's knowledge and sources of information for all US Food and Drug Administration-approved contraceptive methods.

Participants: Seven focus groups and 24 female adolescent participants aged 15-19 years.

Interventions And Main Outcome Measures: Quantitative ranking of all contraceptive methods; qualitative themes from focus group discussions.

Results: Our findings showed a high level of knowledge about a select group of methods, which included LARC methods, and that participants received contraceptive information from peers and family. Participants had more concerns than positive impressions regarding the effectiveness, safety, practicality, and partner reception of the contraceptive methods, with the exception of the condom. Quantitatively, the condom received the highest average rating.

Conclusion: The importance of personal anecdotes in our findings supports the use of outreach and information campaigns; providing medically accurate information and spreading positive personal anecdotes will be key to improving young women's impressions of the safety and acceptability of LARC use. This snapshot of contraceptive knowledge indicates that young women can be mature, informed consumers of sexual and reproductive health care, and through diffusion of innovation could be key players in promoting the most effective means of pregnancy prevention.
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http://dx.doi.org/10.1016/j.jpag.2017.01.003DOI Listing
August 2017

Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection.

PLoS One 2016 16;11(6):e0156801. Epub 2016 Jun 16.

MRC Biostatistics Unit, Cambridge, CB2 0SR, United Kingdom.

Detection of hepatocellular carcinoma (HCC) through screening can improve outcomes. However, HCC surveillance remains costly, cumbersome and suboptimal. We tested whether and how serum Alpha-Fetoprotein (AFP) should be used in HCC surveillance. Record linkage, dedicated pathways for management and AFP data-storage identified i) consecutive highly characterised cases of HCC diagnosed in 2009-14 and ii) a cohort of ongoing HCC-free patients undergoing regular HCC surveillance from 2009. These two well-defined Scottish patient cohorts enabled us to test the utility of AFP surveillance. Of 304 cases of HCC diagnosed over 6 years, 42% (129) were identified by a dedicated HCC surveillance programme. Of these 129, 47% (61) had a detectable lesion first identified by screening ultrasound (US) but 38% (49) were prompted by elevated AFP. Despite pre-HCC diagnosis AFP >20kU/L being associated with poor outcome, 'AFP-detected' tumours were offered potentially curative management as frequently as 'US-detected' HCCs; and had comparable survival. Linearity of serial log10-transformed AFPs in HCC cases and in the screening 'HCC-free' cohort (n = 1509) provided indicators of high-risk AFP behaviour in HCC cases. An algorithm was devised in static mode, then tested dynamically. A case/control series in hepatitis C related disease demonstrated highly significant detection (p<1.72*10-5) of patients at high risk of developing HCC. These data support the use of AFP in HCC surveillance. We show proof-of-principle that an automated and further refine-able algorithmic interpretation of AFP can identify patients at higher risk of HCC. This approach could provide a cost-effective, user-friendly and much needed addition to US surveillance.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911090PMC
July 2017

Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

Kidney Int 2016 May 7;89(5):1125-1135. Epub 2016 Mar 7.

University of Edinburgh/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; Department of Renal Medicine, Royal Infirmary, Edinburgh, UK. Electronic address:

Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.
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http://dx.doi.org/10.1016/j.kint.2016.01.015DOI Listing
May 2016

Balloon angioplasty, with and without stenting, versus medical therapy for hypertensive patients with renal artery stenosis.

Cochrane Database Syst Rev 2014 5(12):CD002944. Epub 2014 Dec 5.

Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.

Background: Atherosclerotic renal artery stenosis is the most common cause of secondary hypertension. Balloon angioplasty with stenting is widely used for the treatment of hypertensive patients with renal artery stenosis but the effectiveness of this procedure in treating hypertension, improving renal function and preventing adverse cardiovascular and renal events remains uncertain. This is an update, to include the results of recent, important large trials, of a review first published in 2003.

Objectives: To compare the effectiveness of balloon angioplasty (with and without stenting) with medical therapy for the treatment of atherosclerotic renal artery stenosis in patients with hypertension. The following outcomes were compared: blood pressure control, renal function, frequency of cardiovascular and renal adverse events, presence or absence of restenosis of the renal artery, side effects of medical therapy, numbers and defined daily doses of antihypertensive drugs.

Search Methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2014) and CENTRAL (2014, Issue 4). Bibliographies were also reviewed and trial authors were contacted for more information.

Selection Criteria: Randomised controlled trials (RCTs) comparing balloon angioplasty with medical therapy in hypertensive patients with haemodynamically significant renal artery stenosis (greater than 50% reduction in luminal diameter) and with a minimum follow-up of six months.

Data Collection And Analysis: Data were extracted independently on trial design, participants, interventions and outcome measures. A formal meta-analysis was completed to assess the effect on blood pressure, renal function and cardiovascular and renal adverse events. Peto's odds ratios (ORs) and corresponding 95% confidence intervals (CI) for dichotomous outcomes and mean differences (MD) and corresponding 95% CIs for continuous variables were calculated.

Main Results: Eight RCTs involving 2222 participants with renal artery stenosis were included in the review. The overall quality of evidence included in this review was moderate. Limited pooling of results was possible due to the variable presentation of some of the trial outcomes. Meta-analysis of the four studies reporting change in diastolic blood pressure (BP) found a small improvement in diastolic BP in the angioplasty group (MD -2.00 mmHg; 95% CI -3.72 to -0.27) whilst the meta-analysis of the five studies reporting change in systolic BP did not find any evidence of significant improvement (MD -1.07 mmHg; 95% CI -3.45 to 1.30). There was no significant effect on renal function as measured by serum creatinine (MD -7.99 µmol/L; 95% CI -22.6 to 6.62). Meta-analysis of the three studies that reported the mean number of antihypertensive drugs found a small decrease in antihypertensive drug requirements for the angioplasty group (MD -0.18; 95% CI -0.34 to -0.03). Repeat angiography was only performed on a small number of participants in a single trial and it was therefore not possible to comment on restenosis of the renal artery following balloon angioplasty. Based on the results of the seven studies that reported cardiovascular and renal clinical outcomes there were no differences in cardiovascular (OR 0.91; 95% CI 0.75 to 1.11) or renal adverse events (OR 1.02; 95% CI 0.75 to 1.38) between the angioplasty and medical treatment groups. A small number of procedural complications of balloon angioplasty were reported (haematoma at the site of catheter insertion (6.5%), femoral artery pseudoaneurysm (0.7%), renal artery or kidney perforation or dissection (2.5%) as well as peri-procedural deaths (0.4%)). No side effects of medical therapy were reported.

Authors' Conclusions: The available data are insufficient to conclude that revascularisation in the form of balloon angioplasty, with or without stenting, is superior to medical therapy for the treatment of atherosclerotic renal artery stenosis in patients with hypertension. However, balloon angioplasty results in a small improvement in diastolic blood pressure and a small reduction in antihypertensive drug requirements. Balloon angioplasty appears safe and results in similar numbers of cardiovascular and renal adverse events to medical therapy.
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http://dx.doi.org/10.1002/14651858.CD002944.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138037PMC
January 2015

Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors.

Kidney Int 2012 Oct 20;82(7):812-8. Epub 2012 Jun 20.

University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, Metabolic Unit, Western General Hospital, Edinburgh, UK.

Tubulointerstitial disease plays an important role in the pathophysiology of diabetic kidney disease. To determine whether biomarkers of tubular injury could predict renal outcome and mortality in patients with type 2 diabetes, we measured urinary levels of kidney injury molecule-1 (KIM-1) and glycoprotein non-metastatic melanoma B (Gpnmb), both normalized to the urinary creatinine, in 978 individuals from the Edinburgh Type 2 Diabetes Study. At baseline, 238 patients had an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 while 147 and 15 patients had microalbuminuria or overt proteinuria, respectively. Both the urine KIM-1 and Gpnmb to creatinine ratios correlated with the urinary albumin to creatinine ratio, the duration of diabetes, and the stringency of glycemic control but not with blood pressure or baseline eGFR. Higher ratios of each marker were associated with a faster decline in kidney function during 4 years of follow-up; however, this was not independent of the urinary albumin to creatinine ratio. Higher KIM-1, but not Gpnmb ratios were associated with an increased risk of mortality, but this association was no longer significant after adjustment for other risk factors, in particular albuminuria. Thus, tubular injury in persons with type 2 diabetes may contribute to the decline in kidney function; however, measuring the urinary concentration of these two tubular biomarkers does not confer additional prognostic information beyond established risk factors.
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http://dx.doi.org/10.1038/ki.2012.218DOI Listing
October 2012

Analysis of the hypervariable region of the Salmonella enterica genome associated with tRNA(leuX).

J Bacteriol 2005 Apr;187(7):2469-82

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.

The divergence of Salmonella enterica and Escherichia coli is estimated to have occurred approximately 140 million years ago. Despite this evolutionary distance, the genomes of these two species still share extensive synteny and homology. However, there are significant differences between the two species in terms of genes putatively acquired via various horizontal transfer events. Here we report on the composition and distribution across the Salmonella genus of a chromosomal region designated SPI-10 in Salmonella enterica serovar Typhi and located adjacent to tRNA(leuX). We find that across the Salmonella genus the tRNA(leuX) region is a hypervariable hot spot for horizontal gene transfer; different isolates from the same S. enterica serovar can exhibit significant variation in this region. Many P4 phage, plasmid, and transposable element-associated genes are found adjacent to tRNA(leuX) in both Salmonella and E. coli, suggesting that these mobile genetic elements have played a major role in driving the variability of this region.
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http://dx.doi.org/10.1128/JB.187.7.2469-2482.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1065210PMC
April 2005