If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Editor's Choice – Cohort Study Examining the Association Between Abdominal Aortic Size and Major Adverse Cardiovascular Events in Patients with Aortic and Peripheral Occlusive and Aneurysmal Disease
Corresponding author. Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, 4811, Australia.
Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, AustraliaThe Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, AustraliaThe Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, AustraliaThe Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Queensland, Australia
The aim of this study was to examine whether there were independent associations between abdominal aortic diameter, size index, and height index and the risk of major adverse events in patients referred for treatment of various types of aortic and peripheral occlusive and aneurysmal disease (APOAD).
Methods
In total, 1 752 participants with a variety of APOADs were prospectively recruited between 2002 and 2020 and had a maximum abdominal aortic diameter, aortic size index (aortic diameter relative to body surface area), and aortic height index (aortic diameter relative to height) measured by ultrasound at recruitment. Participants were followed for a median of 4.6 years (interquartile range 2.0 – 8.0 years) to record outcome events, including major adverse cardiovascular events (MACE), peripheral artery surgery, abdominal aortic aneurysm (AAA) events (rupture or repair), and all cause mortality. The association between aortic size and events was assessed using Cox proportional hazard analysis. The ability of aortic size to improve risk of events classification was assessed using the net reclassification index (NRI).
Results
After adjusting for other risk factors, larger aortic diameter was associated with an increased risk of MACE (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.05 – 1.31), requirement for peripheral artery surgery (HR 2.05, 95% CI 1.90 – 2.22), AAA events (HR 3.01, 95% CI 2.77 – 3.26), and all cause mortality (HR 1.20, 95% CI 1.08 – 1.32). Findings were similar for aortic size and aortic height indices. According to the NRI, all three aortic size measures significantly improved classification of risk of peripheral artery surgery and AAA events but not MACE. Aortic size index, but not aortic diameter or aortic height index, significantly improved the classification of all cause mortality risk.
Conclusion
Larger abdominal aortic diameter, size index, and height index are all independently associated with an increased risk of major adverse events in patients with established vascular disease.
Abdominal aortic diameter has been associated with the risk of adverse events in healthy individuals; however, its predictive ability in patients with established vascular disease is unknown. This prospective observational study found that larger abdominal aortic diameter, size index, and height index were independently associated with an increased risk of major adverse cardiovascular events, peripheral artery surgery, abdominal aortic aneurysm (AAA) events, and all cause mortality over a median follow up of approximately 4.6 years. Abdominal aortic size index significantly improved the classification of risk of peripheral artery surgery, AAA events, and all cause mortality over clinical risk factors alone.
Introduction
Abdominal aortic ultrasound imaging is performed in many high income countries to screen for an abdominal aortic aneurysm (AAA).
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.
Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. The UK Small Aneurysm Trial Participants.
Abdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study.
Abdominal aortic diameter larger than the normal range has been associated with an increased risk of both cardiovascular and all cause mortality in these healthy populations.
Some studies have suggested a J shaped relationship between mortality and abdominal aortic diameter, with small aortic diameter, as well as large aortic diameter, associated with an increased mortality risk
compared with a diameter in the normal range. As a result, abdominal aortic diameter has been suggested as a valuable measure of the risk of major adverse cardiovascular events (MACE), which can be used to help with decisions about the need for primary prevention medical therapies.
The maximum diameter of the ascending aorta, usually reported relative to body surface area (defined as aortic size index) or height (aortic height index), has also been associated with the risk of major adverse events.
Increased aortic diameters on multidetector computed tomographic scan are independent predictors of incident adverse cardiovascular events: the Framingham Heart Study.
However, no previous study has compared the associations of abdominal aortic diameter, size index, and height index with the incidence of major adverse events. Abdominal aortic imaging is commonly performed in patients referred to vascular surgeons for the management of aortic and peripheral occlusive and aneurysmal disease (APOAD). It is unclear if abdominal aortic size in these heterogeneous groups of patients with established vascular disease, all of whom have a higher risk of events than healthy community populations, is predictive of major adverse events. If abdominal aortic size is also predictive of adverse events in patients with established vascular disease it may be useful in risk stratifying them to assist in decisions about the intensity of medical management. The aim of this study was to examine whether there were independent associations between abdominal aortic diameter, size index, and height index and the risk of major adverse events in patients referred to vascular specialists for treatment of various types of APOAD.
Methods
Study design and participants
The study was designed as part of an ongoing prospective cohort investigation that began in 2002 and aimed to identify risk factors associated with the outcome of peripheral vascular disease.
Association of serum lipoprotein (a) with the requirement for a peripheral artery operation and the incidence of major adverse cardiovascular events in people with peripheral artery disease.
To be eligible for the current study participants had to have a diagnosis of an APOAD and be recruited from the outpatient vascular services at The Townsville University Hospital, the Mater Hospital Townsville, or The Royal Brisbane and Women’s Hospital in Queensland, Australia, between February 2002 and November 2020 and have attended at least one follow up review. Participants presenting with any of the following APOADs were eligible: (1) visceral artery disease (defined as ≥ 50% stenosis or occlusion of one or more renal or mesenteric arteries); (2) carotid artery stenosis (defined as ≥ 50% stenosis or occlusion of at least one carotid artery associated with or without focal neurological symptoms, such as stroke, transient ischaemic attack, or amaurosis fugax);
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.
femoral artery aneurysm was defined by a common femoral or superficial femoral artery diameter of ≥ 15 mm, and popliteal artery aneurysm was defined as popliteal artery diameter ≥ 9 mm;
(5) chronic limb threatening ischaemia (CLTI; rest pain, ischaemic ulceration, or gangrene secondary to peripheral artery disease, defined by the absence of lower limb pulses, an ankle brachial pressure index < 0.9 and/or significant stenosis (≥ 50%) or occlusion of lower limb arteries).
The APOAD was diagnosed by a Royal Australasian College of Surgeons accredited vascular surgeon based on symptoms, clinical examination, and investigations, as previously described.
Association of serum lipoprotein (a) with the requirement for a peripheral artery operation and the incidence of major adverse cardiovascular events in people with peripheral artery disease.
Written informed consent was obtained from all participants upon entry into the study. The study was performed in accordance with the Declaration of Helsinki, and ethical approval was granted from the relevant institutional ethics committees (HREC/13/QTHS/125 and HREC/14/QTHS/203).
Risk factors and medications
Clinical characteristics collected included age, sex, diabetes, hypertension, smoking, coronary heart disease (CHD), stroke and currently prescribed medications.
Smoking classification was based on smoking history and defined as current smoker (smoked within the last month), previous smoker, or never smoked. Hypertension, diabetes, and stroke were defined by documented history or medical treatment for these conditions. CHD was defined by a history of myocardial infarction (MI), angina, or coronary revascularisation. Prescriptions of aspirin, other antiplatelet drugs, warfarin, or novel oral anticoagulants were recorded and defined as receipt of an antithrombotic drug. Prescription of statins was also recorded. All medication prescriptions were obtained from medical records at the time of recruitment. Body mass index was measured as described previously.
Maximum anterior to posterior and transverse infrarenal aortic diameters were measured by experienced sonographers using ultrasound machines employed in the vascular laboratories at each site using a standard protocol, as described previously.
The reproducibility of aortic diameter measurements was assessed in each vascular laboratory, with interobserver reproducibility coefficients being < 4 mm as previously reported.
Aortic size index was calculated by dividing maximum aortic diameter (cm) by body surface area (m2), and aortic height index by dividing maximum aortic diameter (cm) by height (m) as described previously.
Participants were offered follow up three months after their initial outpatient visit and then annually as the standard care. Outcome data were recorded during clinical reviews on prospectively defined case report forms. Hospital charts and electronic records were also reviewed by a vascular specialist. Outcome data were also obtained from linked hospital admission records from the Queensland Hospital Admitted Patient Data Collection, which is regularly audited to minimise inaccuracies.
Association of serum lipoprotein (a) with the requirement for a peripheral artery operation and the incidence of major adverse cardiovascular events in people with peripheral artery disease.
The primary outcome was the first occurrence of a MACE, defined as including MI, stroke, or cardiovascular death. The secondary outcomes included peripheral artery surgical operations, AAA events, and all cause mortality. Peripheral artery surgical operations were defined to include both open surgical and endovascular lower limb peripheral revascularisations, carotid artery revascularisation, AAA, and other aneurysm repairs.
Editor's Choice - Metformin prescription is associated with a reduction in the combined incidence of surgical repair and rupture related mortality in patients with abdominal aortic aneurysm.
Decisions about requirement for operative interventions were at the discretion of the treating consultant surgeon but were in line with current international guidelines,
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.
Editor's Choice - Metformin prescription is associated with a reduction in the combined incidence of surgical repair and rupture related mortality in patients with abdominal aortic aneurysm.
Editor's Choice - 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
The aim was to have adequate power to test the hypothesis that abdominal aortic size was associated with MACE. Previous studies suggest that approximately 20% of people with APOADs have a MACE during short term follow up.
Monte-Carlo simulations suggest that a multivariable regression model is powered sufficiently when 10 outcome events per degree of freedom of the predictor variables are observed.
Conservatively, assuming an incidence of MACE of 10% and planning to adjust for age, sex, presenting problem (five options), current smoking, diabetes, hypertension, CHD, stroke, and statin and antithrombotic drug prescriptions in the regression models, it was estimated that a sample size of at least 1 500 participants would be required to have adequate power to test the main hypothesis.
Data analysis
Data were analysed using SPSS version 25 (IBM, Armonk, NY, USA) and Stata v16.1 (StataCorp, College Station, TX, USA). Continuous data were not normally distributed, as confirmed using the Shapiro–Wilk test, and were presented as median and interquartile range (IQR) and compared between groups using the Kruskal–Wallis test. The distribution of categorical variables between groups was compared using Pearson’s chi square test. Kaplan–Meier curves with log rank test were used to compare the proportion of participants having outcome events. Cox proportional hazard analyses assessed the association between aortic size and outcome events adjusted for age, sex, presenting problem, current smoking, diabetes, hypertension, CHD, stroke, and statin and antithrombotic prescriptions. Results were presented as hazard ratios (HRs) and 95% confidence intervals (CIs). The ability of different aortic size measures to predict outcome events was examined by calculating the net reclassification index (NRI).
Association of chronic kidney disease categories defined with different formulae with major adverse events in patients with peripheral vascular disease.
NRI was used to assess whether the addition of the different measures of aortic size to a model incorporating traditional risk factors significantly improved the ability to predict adverse events. A sensitivity analysis was performed to test whether the main findings were similar when participants with more urgent presentations (i.e., AAA measuring ≥ 55 mm, symptomatic carotid artery disease, or CLTI) were excluded. Analyses restricted to male and female participants were also performed. A p value < .05 was considered significant for all of these analyses.
Results
Relationship between abdominal aortic size quartiles and risk factors at recruitment
A total of 1 752 participants presenting with visceral artery disease (n = 85, 4.8%), carotid artery disease (n = 162, 9.2%), aortic or peripheral aneurysm (n = 1 038, 59.2%), intermittent claudication (n = 332, 18.9%), and CLTI (n = 135, 7.7%) were included. Table 1, Table 2 show the relationship between abdominal aortic diameter and size index quartiles and risk factors and medications recorded at the time of recruitment. Older age, male sex, current smoking, CHD, and previous stroke were significantly more common, while diabetes was significantly less common, in participants in higher compared with lower quartiles of aortic diameter and size indices (Table 1, Table 2).
Table 1Risk factors and medications recorded at recruitment in relation to aortic diameter in 1 752 participants with various types of aortic and peripheral occlusive and aneurysmal disease
Table 2Risk factors and medications recorded at recruitment in relation to aortic size index in 1 752 participants with various types of aortic and peripheral occlusive and aneurysmal disease
Association of abdominal aortic size with outcome events
Participants were followed for a median of 4.6 years (IQR 2.0 – 8.0). During this period 235 (13.4%), 112 (6.4%), 394 (22.5%), 98 (5.6%), 482 (27.5%), and 16 (0.9%) participants had at least one MI, stroke, lower limb peripheral revascularisation, carotid artery revascularisation, AAA repair, and AAA rupture, respectively. There were 639 (36.5%) deaths of which 349 were due to cardiovascular causes. Larger aortic diameter, size index, and height index were significantly associated with a greater risk of all outcome events in both unadjusted and adjusted analyses (see Figure 1, Figure 2, Figure 3; Table 3).
Figure 1Cumulative Kaplan–Meier estimates of the freedom from (A) major adverse cardiovascular event (MACE); (B) peripheral artery surgery; (C) abdominal aortic aneurysm (AAA) events; and (D) all cause mortality according to quartile of abdominal aortic diameter.
Figure 2Cumulative Kaplan–Meier estimates of the freedom from (A) major adverse cardiovascular event (MACE); (B) peripheral artery surgery; (C) abdominal artery aneurysm (AAA) events; and (D) all cause mortality according to quartile of abdominal aortic size index.
Figure 3Cumulative Kaplan–Meier estimates of the freedom from (A) major adverse cardiovascular event (MACE); (B) peripheral artery surgery; (C) abdominal aortic aneurysm (AAA) events; and (D) all cause mortality according to quartile of abdominal aortic height index.
Table 3Association between aortic size measurement and major adverse events during the follow up of 1 752 participants with various types of aortic and peripheral occlusive and aneurysmal disease
Event
Aortic diameter
Aortic size index
Aortic height index
Unadjusted
Adjusted
Unadjusted
Adjusted
Unadjusted
Adjusted
HR (95% CI)
p value
HR (95% CI)
p value
HR (95% CI)
p value
HR (95% CI)
p value
HR (95% CI)
p value
HR (95% CI)
p value
Major adverse cardiovascular events
1.12 (1.04–1.21)
.004
1.17 (1.05–1.31)
.006
1.19 (1.10–1.29)
<.001
1.28 (1.14–1.42)
<.001
1.14 (1.06–1.23)
.001
1.19 (1.07–1.34)
.002
Any peripheral artery surgical procedure
1.75 (1.64–1.87)
<.001
2.05 (1.90–2.22)
<.001
1.70 (1.59–1.82)
<.001
2.07 (1.91–2.25)
<.001
1.73 (1.62–1.86)
<.001
2.05 (1.90–2.22)
<.001
AAA event
3.32 (3.11–3.55)
<.001
3.01 (2.77–3.26)
<.001
3.37 (3.13–3.62)
<.001
3.04 (2.78–3.32)
<.001
3.41 (3.18–3.66)
<.001
2.98 (2.75–3.24)
<.001
All cause mortality
1.18 (1.10–1.26)
<.001
1.20 (1.08–1.32)
<.001
1.27 (1.19–1.36)
<.001
1.28 (1.16–1.41)
<.001
1.20 (1.12–1.28)
<.001
1.20 (1.09–1.32)
<.001
Analyses adjusted for age, sex, presentation, diabetes, hypertension, coronary heart disease, previous stroke, current smoking, statin, and antithrombotic prescriptions. The aortic size measurements were reported relative to an increase of approximately one standard deviation (aortic diameter 15.8 mm; aortic size index 0.833 cm/m2; aortic height index 0.917 cm/m). HR = hazard ratio; CI = confidence interval; AAA = abdominal aortic aneurysm.
Ability of abdominal aortic size to predict outcome events
Based on the NRI, none of the aortic size measures significantly added to the ability of clinical risk factors alone to classify the risk of MACE (Table 4). In contrast, all three aortic size measures significantly improved the classification of risk of peripheral artery surgery and AAA events (Table 4). Only aortic size index, but not aortic diameter or aortic height index, significantly improved the classification of all cause mortality risk (NRI 0.11, 95% CI 0.02 – 0.21; p = .023).
Table 4Discrimination and reclassification of 1 752 participants with various types of aortic and peripheral occlusive and aneurysmal disease for different major adverse outcomes using aortic diameter, aortic size index, and aortic height index
Models
Net reclassification index (95% CI)
p value
Major adverse cardiovascular events
Clinical risk factors only
–
Clinical risk factors + aortic diameter
–0.02 (–0.12–0.08)
.65
Clinical risk factors + aortic size index
0.02 (–0.08–0.12)
.69
Clinical risk factors + aortic height index
–0.05 (–0.15–0.06)
.81
Requirement for peripheral artery surgery
Clinical risk factors only
–
Clinical risk factors + aortic diameter
0.54 (0.45–0.64)
<.001
Clinical risk factors + aortic size index
0.54 (0.44–0.63)
<.001
Clinical risk factors + aortic height index
0.53 (0.43–0.62)
<.001
Abdominal aortic aneurysm events
Clinical risk factors only
–
Clinical risk factors + aortic diameter
1.46 (1.35–1.56)
<.001
Clinical risk factors + aortic size index
1.37 (1.27–1.47)
<.001
Clinical risk factors + aortic height index
1.47 (1.36–1.57)
<.001
All cause mortality
Clinical risk factors only
–
Clinical risk factors + aortic diameter
0.03 (–0.07–0.13)
.57
Clinical risk factors + aortic size index
0.11 (0.02–0.21)
.023
Clinical risk factors + aortic height index
0.04 (–0.06–0.14)
.40
Clinical risk factors includes age, sex, presentation, diabetes, hypertension, coronary heart disease, previous stroke, current smoking, statin, and antithrombotic prescriptions.
In analyses restricted to participants with non-urgent presentations, larger aortic diameter, size index, and height index were significantly associated with a greater risk of all outcome events in both unadjusted and adjusted analyses with the exception of aortic diameter and the risk of MACE (Supplementary Table 1). Based on NRI, aortic diameter and aortic height index, but not aortic size index, significantly added to the ability of clinical risk factors alone to classify the risk of MACE (Supplementary Table 2). All three aortic size measures significantly improved the classification of risk of peripheral artery surgery and AAA events (Supplementary Table 2). None of the aortic size measures significantly improved the classification of all cause mortality risk (Supplementary Table 2).
In analyses restricted to male participants, larger aortic size index, but not aortic diameter or aortic height index, was significantly associated with a greater risk of MACE in adjusted analyses (Supplementary Table 3). Larger aortic diameter, size index, and height index were significantly associated with a greater risk of all other outcome events in both unadjusted and adjusted analyses (Supplementary Table 3). In female participants, larger aortic diameter, size index and height index were significantly associated with a greater risk of all outcome events in both unadjusted and adjusted analyses (Supplementary Table 4). All three aortic size measures significantly improved the classification of risk of peripheral artery surgery and AAA events in both male and female participants (Supplementary Table 5). Aortic size index and height index significantly improved the classification of risk of all cause mortality over clinical risk factors alone only in female participants (Supplementary Table 5).
Discussion
The current study found that larger abdominal aortic diameter, size index, and height index were associated with increased risks of MACE, peripheral artery surgery, AAA events, and all cause mortality over a median follow up of approximately five years in a large number of participants with a variety of APOAD presentations. These associations were independent of traditional risk factors. All three abdominal aortic size measures significantly improved the classification of risk of peripheral artery surgery and AAA events over use of clinical risk factors alone. Only abdominal aortic size index significantly improved the classification of risk of all cause mortality over clinical risk factors alone. Findings were broadly similar when restricted to participants with non-urgent presentations and men and women. The findings demonstrate the value of measuring abdominal aortic size in patients referred to specialist vascular services.
Previous studies have demonstrated the independent association of large abdominal aortic diameter with increased risk of death in community populations screened for AAA.
Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. The UK Small Aneurysm Trial Participants.
The novel findings of the current study are firstly that the association between large abdominal aortic diameter and increased mortality risk is also present in populations with established vascular disease, including patients with occlusive artery disease. Approximately 40% of the participants in the current study had occlusive rather than aneurysmal disease. Furthermore, abdominal aortic size in these participants was independently associated with the risk of not only death, but also MACE, peripheral artery surgery, and AAA events. The findings highlight that patients with larger abdominal aortic diameter in the non-aneurysmal, as well as aneurysmal range, referred to vascular services might benefit from intensive medical management to prevent cardiovascular events such as MI, stroke, requirement for surgery, and death.
The current study also provides novel information on the ability of abdominal aortic size and height index in reclassifying the risk of adverse events. Abdominal aortic size significantly improved the classification of risk of peripheral artery surgery and AAA events over clinical risk factors alone. Only abdominal aortic size index significantly improved the classification of all cause mortality risk. This suggests that aortic size index, rather than abdominal aortic diameter or abdominal aortic height index, may be most useful for classifying the risk of adverse events. The findings need to be validated in other cohorts.
A number of limitations of the current study should be acknowledged. The study was designed to include a heterogeneous group of patients referred for management of different APOADs. The findings may not be generalisable to other cohorts of more homogenous presentations of peripheral artery disease. The current study is an observational investigation and while the associations presented were adjusted for other key cardiovascular risk factors it is impossible to exclude residual confounding.
In conclusion, this study shows that larger abdominal aortic diameter, size index and height index are all independently associated with an increased risk of MACE, peripheral artery surgery, AAA events and all cause mortality in patients with established vascular disease.
Funding
This study was supported by funding from the National Health and Medical Research Council (1063476 and 1180736) and the Queensland Government (Australia).
Conflicts of interest
None.
Acknowledgements
Jonathan Golledge holds a Practitioner Fellowship from the National Health and Medical Research Council (1117061) and a Senior Clinical Research Fellowship from the Queensland Government. TPS holds a Junior Doctor Research Fellowship from the Queensland Government.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
Editor's Choice - European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms.
Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. The UK Small Aneurysm Trial Participants.
Abdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study.
Increased aortic diameters on multidetector computed tomographic scan are independent predictors of incident adverse cardiovascular events: the Framingham Heart Study.
Association of serum lipoprotein (a) with the requirement for a peripheral artery operation and the incidence of major adverse cardiovascular events in people with peripheral artery disease.
Editor's Choice - Metformin prescription is associated with a reduction in the combined incidence of surgical repair and rupture related mortality in patients with abdominal aortic aneurysm.
Editor's Choice - 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
Association of chronic kidney disease categories defined with different formulae with major adverse events in patients with peripheral vascular disease.
To submit a comment for a journal article, please use the space above and note the following:
We will review submitted comments as soon as possible, striving for within two business days.
This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
We require that commenters identify themselves with names and affiliations.
00750-4&id=gr1.jpg){kind=link}
00750-4&id=gr2.jpg){kind=link}
00750-4&id=gr3.jpg){kind=link}