Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation.

Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.

Does Individualization of Cup Position Affect Prosthetic or Bone Impingement Following Total Hip Arthroplasty?

BACKGROUND: Spinopelvic (SP) mobility patterns during postural changes affect three-dimensional acetabular component position, the incidence of prosthetic impingement, and total hip arthroplasty (THA) instability. Surgeons have commonly placed the acetabular component in a similar "safe zone" for most patients. Our purpose was to determine the incidence of bone and prosthetic impingement with various cup orientations and determine if a preoperative SP analysis with individualized cup orientation lessens impingement. METHODS: A preoperative SP evaluation of 78 THA subjects was performed. Data were analyzed using a software program to determine the prevalence of prosthetic and bone impingement with a patient individualized cup orientation versus 6 commonly selected cup orientations. Impingement was correlated with known SP risk factors for dislocation. RESULTS: Prosthetic impingement was least with the individualized choice of cup position (9%) versus preselected cup positions (18%-61%). The presence of bone impingement (33%) was similar in all groups and not affected by cup position. Factors associated with impingement in flexion were age, lumbar flexion, pelvic tilt (stand to flexed seated), and functional femoral stem anteversion. Risk factors in extension included standing pelvic tilt, standing SP tilt, lumbar flexion, pelvic rotation (supine to stand and stand to flexed seated), and functional femoral stem anteversion. CONCLUSION: Prosthetic impingement is reduced with individualized cup positioning based on SP mobility patterns. Bone impingement occurred in one-third of patients and is a noteworthy consideration in preoperative THA planning. Known SP risk factors for THA instability correlated with the presence of prosthetic impingement in both flexion and extension.

What is the Value of a Balanced Total Knee Arthroplasty? Getting It Right the First Time.

BACKGROUND: Instability is a leading cause of early failure following total knee arthroplasty (TKA). Enabling technologies can improve accuracy, but their clinical value remains undetermined. The purpose of this study was to determine the value of achieving a balanced knee joint at the time of TKA. METHODS: A Markov model was developed to determine the value from reduced revisions and improved outcomes associated with TKA joint balance. Patients were modeled for the first 5 years following TKA. The threshold to determine cost-effectiveness was set at an incremental cost effectiveness ratio of $50,000/quality-adjusted life year (QALY). A sensitivity analysis was performed to evaluate the influence of QALY improvement (ΔQALY) and Revision Rate Reduction on additional value generated compared to a conventional TKA cohort. The impact of each variable was evaluated by iterating over a range of ΔQALY (0 to 0.046) and Revision Rate Reduction (0% to 30%) and calculating the value generated while satisfying the incremental cost effectiveness ratio threshold. Finally, the impact of surgeon volume on these outcomes was analyzed. RESULTS: The total value of a balanced knee for the first 5 years was $8,750, $6,575, and $4,417 per case, for low, medium, and high-volume surgeons, respectively. Change in QALY accounted for greater than 90% of the value gain with a reduction in revisions making up the rest in all scenarios. The economic contribution of revision reduction was relatively constant regardless of surgeon volume ($500/case). CONCLUSION: Achieving a balanced knee had the greatest impact on ΔQALY over early revision rate. These results can help assign value to enabling technologies with joint balancing capabilities.

A prospective natural history study of coronary atherosclerosis following liver transplantation.

BACKGROUND & AIMS: Cardiovascular disease remains a leading cause of mortality following liver transplantation (LT). Whether it may be partially attributable to accelerated development of subclinical coronary artery disease is unclear. We sought to assess the longitudinal effect of LT on coronary plaque burden. METHODS: A prospective observational study was conducted in 30 asymptomatic patients who underwent computed tomographic coronary angiography (CTCA) pre- and a median 4-years following LT. Serial changes were quantified using coronary artery calcium score (CACS) and semi-quantitative CTCA scores, in a blinded fashion. High-risk plaque (HRP) characteristics were also assessed. Plaque progression was defined using prognostically significant cut-offs. RESULTS: In the study population (age 59.8 ± 8 years, 80% male), 93 of 459 coronary segments had plaque at baseline. On follow-up CTCA, 68 (+73.1%) new lesions appeared in segments without plaque initially. Nineteen (63.3%) patients demonstrated a clinically significant rise in plaque burden on CACS and semi-quantitative indices on CTCA (all p<0.001). CAD-RADS score rose to ≥4 (≥70% stenosis) in 9 (30%) patients, necessitating ischemia-guided revascularization in 3 (10%) patients. While the absence of coronary calcification or plaque pre-LT was protective, presence of HRP and development of post-transplant metabolic syndrome were both strong independent predictors of atherosclerosis progression. CONCLUSIONS: Our findings suggest that LT is associated with early progression of coronary atherosclerosis. Accelerated progression was noted particularly in those with HRP and post-transplant metabolic syndrome. Understanding the mechanisms of this novel observation and the potential role of preventive cardiovascular therapies in this population merit further study.

Causes and consequences of variation in heterospecific pollen receipt in Oenothera fruticosa.

PREMISE: Heterospecific pollen transfer, the transfer of pollen between species, is common among co-flowering plants, yet the amount of pollen received is extremely variable among species. Intraspecific variation in heterospecific pollen receipt can be even greater, but we lack an understanding of its causes and fitness consequences in wild populations. METHODS: We examined potential drivers of variation in heterospecific pollen receipt in Oenothera fruticosa. We evaluated the relationship between heterospecific and conspecific pollen receipt and considered how visitation by different pollinator groups, local floral neighborhood composition, and flowering phenology affect the total amount and proportion of heterospecific pollen received. Finally, we tested whether variation in heterospecific pollen receipt translated into lower seed production. RESULTS: Heterospecific pollen was ubiquitous on O. fruticosa stigmas, but the amount received was highly variable and unrelated to conspecific pollen receipt. Heterospecific pollen receipt depended on pollinator type, the proportion of nearby conspecific flowers, and flowering date. Significant interactions revealed that the effects of pollinator type and neighborhood were not independent, further contributing to variation in heterospecific pollen. Naturally occurring levels of heterospecific pollen were sufficient to negatively impact seed set, but large amounts of conspecific pollen counteracted this detrimental effect. CONCLUSIONS: Although selection could act on floral traits that attract quality pollinators and promote synchronous flowering in O. fruticosa, the risk of heterospecific pollen is equally dependent on local floral context. This work highlights how extrinsic and intrinsic factors contribute to intraspecific variation in heterospecific pollen receipt in wild plants, with significant fitness consequences.

The Reconstruction of a 12-Lead Electrocardiogram from a Reduced Lead Set Using a Focus Time-Delay Neural Network.

BACKGROUND: The 12-lead electrocardiogram (ECG) is the gold-standard ECG method used by cardiologists. However, accurate electrode placement is difficult and time consuming, and can lead to incorrect interpretation. OBJECTIVES: The objective of this study was to accurately reconstruct a full 12-lead ECG from a reduced lead set. METHODS: Five-electrode placement was used to generate leads I, II, III, aVL, aVR, aVF and V2. These seven leads served as inputs to the focus time-delay neural network (FTDNN) which derived the remaining five precordial leads (V1, V3-V6). An online archived medical database containing 549 cases of ECG recordings was used to train, validate and test the FTDNN. RESULTS: After removing outliers, the reconstructed leads exhibited correlation values of between 0.8609 and 0.9678 as well as low root mean square error values of between 123 µV and 245 µV across all cases, for both healthy controls and cardiovascular disease subgroups except the bundle branch block disease subgroup. The results of the FTDNN method compared favourably to those of prior lead reconstruction methods. CONCLUSIONS: A standard 12-lead ECG was successfully reconstructed with high quantitative correlations from a reduced lead set using only five electrodes, of which four were placed on the limbs. Less reliance on precordial leads will aid in the reduction of electrode placement errors, ultimately improving ECG lead accuracy and reduce the number of cases that are incorrectly diagnosed.

The effects of sublingual nitroglycerin administration in coronary computed tomography angiography.

PURPOSE: The purpose of our study was to compare coronary luminal diameters in patients undergoing coronary computed tomography angiography (CCTA) performed with different sublingual nitroglycerin (NTG) spray regimens. MATERIALS AND METHODS: We retrospectively reviewed CCTA studies performed in two historical groups (Group 1, single dose nitroglycerin 2 min prior to CCTA, and Group 2, single dose 10 min prior), and a current protocol group (Group 3, single dose at 2 and 10 min prior). Thirty patients were evaluated per group. Two blinded readers measured coronary luminal diameters with comparison of diameter measurements. A third blinded reader assessed image quality of coronary artery segments. RESULTS: Significant group-level differences in median luminal diameters were identified. Higher median diameters (95% CI) across all segments of 0.40 mm (0.20, 0.60) for Group 2 versus 1 and 0.50 mm (0.30, 0.70) for Group 3 versus 1 were recorded (both P < 0.001). No significant differences in median luminal diameters were found between Groups 2 and 3. No significant differences in image quality were found among the groups apart from higher image quality for the distal LAD for both Groups 2 and 3 compared to Group 1. CONCLUSION: Sublingual nitroglycerin spray administered as a single dose at 10 minute dilates coronary arteries more than when only administered at 2 min prior to CCTA. Combined two doses at 10 and 2 min prior to CCTA do not yield further dilatation of coronary arteries.

Highly Accelerated Breath-Hold Noncontrast Electrocardiographically- and Pulse-Gated Balanced Steady-State Free Precession Magnetic Resonance Angiography of the Thoracic Aorta: Comparison With Electrocardiographically-Gated Computed Tomographic Angiography.

OBJECTIVE: The aim of this study was to evaluate agreement of measured thoracic aortic caliber in patients with aortic disease, using electrocardiographically-(ECG) and pulse-gated breath-hold noncontrast balanced steady-state free precession MRA (ECG-MRA, P-MRA) at 1.5 T, compared with ECG-gated computed tomographic angiography (CTA). METHODS: Thirty-one patients underwent ECG-MRA, P-MRA, and CTA. Two readers independently measured aortic caliber in 7 segments, with agreement between techniques and readers evaluated. Image quality was qualitatively assessed. RESULTS: There was overall excellent agreement among ECG-MRA, P-MRA, and CTA for measured aortic caliber (Lin's concordance correlation coefficient ≥0.94, all comparisons); however, lower concordance was noted at the annulus (Lin's concordance correlation coefficient <0.6) at segmental assessment. There was excellent interreader agreement for aortic caliber for all 3 techniques (intraclass correlation coefficient >0.94). Image quality was poorer for both MRA techniques compared with CTA, particularly at the aortic root. CONCLUSIONS: Electrocardiographically-gated MRA and P-MRA at 1.5 T achieve comparable thoracic aortic measurements to gated CTA in clinical patients, despite inferior image quality.

Evaluation of Modified Look-Locker Inversion Recovery and Arrhythmia-Insensitive Rapid Cardiac T1 Mapping Pulse Sequences in Cardiomyopathy Patients.

OBJECTIVE: The aim of this study was to compare the performance of arrhythmia-insensitive rapid (AIR) and modified Look-Locker inversion recovery (MOLLI) T1 mapping in patients with cardiomyopathies. METHODS: In 58 patients referred for clinical cardiac magnetic resonance imaging at 1.5 T, we compared MOLLI and AIR native and postcontrast T1 measurements. Two readers independently analyzed myocardial and blood T1 values. Agreement between techniques, interreader agreement per technique, and intrascan agreement per technique were evaluated. RESULTS: The MOLLI and AIR T1 values were strongly correlated (r = 0.98); however, statistically significantly different T1 values were derived (bias 80 milliseconds, pooled data, P < 0.01). Both techniques demonstrated high repeatability (MOLLI, r = 1.00 and coefficient of repeatability [CR] = 72 milliseconds; AIR, r = 0.99 and CR = 184.2 milliseconds) and produced high interreader agreement (MOLLI, r = 1.00 and CR = 51.7 milliseconds; AIR, r = 0.99 and CR = 183.5 milliseconds). CONCLUSIONS: Arrhythmia-insensitive rapid and MOLLI sequences produced significantly different T1 values in a diverse patient cohort.

Anthony Sclafani: Consummate scientist.

In this article we review the scientific contributions of Anthony Sclafani, with specific emphasis on his early work on the neural substrate of the ventromedial hypothalamic (VMH) hyperphagia-obesity syndrome, and on the development of diet-induced obesity (DIO). Over a period of 20 years Sclafani systematically investigated the neuroanatomical basis of the VMH hyperphagia-obesity syndrome, and ultimately identified a longitudinal oxytocin-containing neural tract contributing to its expression. This tract has since been implicated in mediating the effects of at least two gastrointestinal satiety factors. Sclafani was one of the first investigators to demonstrate DIO in rats as a result of exposure to multiple palatable food items (the "supermarket diet"), and concluded that diet palatability was the primary factor responsible for DIO. Sclafani went on to investigate the potency of specific carbohydrate and fat stimuli for inducing hyperphagia, and in so doing discovered that post-ingestive nutrient effects contribute to the elevated intake of palatable food items. To further investigate this effect, he devised an intragastric infusion system which allowed the introduction of nutrients into the gut paired with the oral intake of flavored solutions, an apparatus her termed the "electronic esophagus". Sclafani coined the term "appetition" to describe the effect of intestinal nutrient sensing on post-ingestive appetite stimulation. Sclafani's productivity in the research areas he chose to investigate has been nothing short of extraordinary, and his studies are characterized by inventive hypothesizing and meticulous experimental design. His results and conclusions, to our knowledge, have never been contradicted.

Randall Sakai, chronic social stress, and the research tradition of Curt Richter.

This paper describes Randall Sakai's professional career from graduate school at the University of Pennsylvania, through postdoctoral work at Rockefeller University, and to being an independent investigator at the University of Cincinnati. He was fortunate in having Alan Epstein, Bruce McEwen, and Eliot Stellar as mentors. Early in Sakai's graduate work, Epstein and Stellar introduced him to Curt Richter, the legendary investigator at Johns Hopkins. This early introduction to Richter and his tradition of research was crucial for Sakai's scientific development. We review Sakai's research with the Visible Burrowing System (VBS) at Cincinnati. This was the most original of Sakai's research interests. His experimental proficiency in the investigation of salt appetite, food intake, and obesity led him to focus on the effect of chronic social stress on food intake, body composition, metabolism, and the distribution of fat. He and his colleagues, many of them his students, were able to demonstrate that chronic social stress produced changes in metabolism and fat distribution that were characteristic of an incipient metabolic syndrome that could lead to obesity. This did not solve the problem, but showed the way to further investigation. This opening up of problems to experimental investigation was a hallmark of Richter's research. Thus, Sakai worked in the mainstream of the research tradition of Richter. He did what he revered.

Adolf Meyer's Influence on Curt Richter: Selection, Support, and Mentoring.

Adolph Meyer influenced Curt Richter from the time Richter became a graduate student in Psychology at Johns Hopkins in 1919 until Meyer retired in 1941. Meyer was on Richter's thesis committee. After Richter received his degree, Meyer selected him to replace J.B. Watson. During the next 20 years, Meyer gave Richter strong support in terms of equipment, laboratory space for animal research, and opportunities to teach medical students, attend clinical rounds, and do clinical research. It is less well known that Meyer also mentored Richter's scientific and professional development. Meyer's mentoring was so successful that Richter adopted the major scientific ideas of Meyer, especially psychobiology, distrust of theory, and respect for experiment. Thus, Meyer's ideas became the framework for Richter's famous research program that produced his major discoveries of behavior exerting homeostatic controls, psychoendocrinology, and biological clocks.

DEVELOPMENT OF REFERENCE RANGES FOR PLASMA TOTAL CHOLINESTERASE AND BRAIN ACETYLCHOLINESTERASE ACTIVITY IN FREE-RANGING CARNABY'S BLACK-COCKATOOS (CALYPTORHYNCHUS LATIROSTRIS).

Published avian reference ranges for plasma cholinesterase (ChE) and brain acetylcholinesterase (AChE) are numerous. However, a consistently reported recommendation is the need for species- and laboratory-specific reference ranges because of variables, including assay methods, sample storage conditions, season, and bird sex, age, and physiologic status. We developed normal reference ranges for brain AChE and plasma total ChE (tChE) activity for Carnaby's Black-Cockatoos (Calyptorhynchus latirostris) using a standardized protocol (substrate acetylthiocholine at 25 C). We report reference ranges for brain AChE (19-41 µmol/min per g, mean 21±6.38) and plasma tChE (0.41-0.53 µmol/min per mL, mean 0.47±0.11) (n=15). This information will be of use in the ongoing field investigation of a paresis-paralysis syndrome in the endangered Carnaby's Black-Cockatoos, suspected to be associated with exposure to anticholinesterase compounds and add to the paucity of reference ranges for plasma tChE and brain AChE in Australian psittacine birds.

Right ventricular global longitudinal strain is an independent predictor of right ventricular function: a multimodality study of cardiac magnetic resonance imaging, real time three-dimensional echocardiography and speckle tracking echocardiography.

OBJECTIVES: Accurate assessment of right ventricular (RV) systolic function is important, as it is an established predictor of mortality in cardiac and respiratory diseases. We aimed to compare speckle tracking-derived longitudinal deformation measurements with traditional two-dimensional (2D) echocardiographic parameters, as well as real time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR)-derived RV volumes and ejection fraction (EF). METHOD: Subjects referred for CMR also underwent echocardiography. On both RT3DE and CMR, we measured RV volumes and EF. On 2D echocardiography, we analyzed RV fractional area change, RV internal diastolic diameter, tricuspid annular plane systolic excursion, tricuspid annular tissue Doppler-derived velocity, myocardial performance index, and RV global longitudinal strain (RV GLS). RESULTS: Sixty subjects were recruited (mean age = 45 ± 10 years; 60% male). RV GLS (R = -0.69, P < 0.001) and RT3DE RVEF (R = 0.56, P < 0.001) correlated well with CMR RVEF. RT3DE RV end-diastolic (RVEDV) and end-systolic (RVESV) volumes also correlated with CMR RV volumes: RVEDV, R = 0.74, P < 0.001 and RVESV, R = 0.84, P < 0.001. In addition, RV GLS best predicted the presence of RV dysfunction, defined as RVEF <48% on CMR (hazard ratio = 7.0 [1.5-31.7], P < 0.01). On receiver operator characteristic analysis, a RV GLS of -20% was the most sensitive and specific predictor of RV dysfunction (AUC 0.8 [0.57-1.0], P < 0.02). CONCLUSION: RVEF and volumes estimated on RT3DE were closely correlated with CMR measurements. When compared to more traditional markers of RV systolic function and RT3DE, RVGLS produced the highest correlation with CMR RVEF and was a good predictor of RV dysfunction. RV GLS should be considered a complementary modality to RT3DE and CMR in the assessment of RV systolic function.

Prediction of postoperative pain after Mohs micrographic surgery with 2 validated pain anxiety scales.

BACKGROUND: Anxiety toward pain has been shown in several studies to increase postoperative pain after surgical procedures. This anxiety can be measured by several validated questionnaires, the Pain Catastrophizing Scale (PCS) and the Pain Anxiety Symptoms Scale (PASS). Higher scores on these scales correlate with increased pain after surgery, but this has not yet been demonstrated in dermatologic surgery. OBJECTIVE: To assess whether pain anxiety will predict postoperative pain after Mohs micrographic surgery (MMS). MATERIALS AND METHODS: Patients at 2 private Mohs practices were recruited to fill out 2 pain questionnaires, the PCS and the PASS. Their postoperative pain was assessed after MMS. RESULTS: Three hundred fifty-six patients completed the study. Overall, most patients experienced little postoperative pain after Mohs surgery. However, for people with high anxiety toward pain, they also experienced statistically significant greater postoperative pain. Other factors that contributed to greater postoperative pain included female gender and lower extremity location. Second intention healing had lower pain than other repair types. CONCLUSION: This study shows that postoperative pain is affected by pain anxiety, even in dermatologic surgery. However, most patients still had very little discomfort after surgery, further supporting MMS as an effective and safe procedure with relatively few postoperative problems.

Synergistic relationship between the Columbia University Appetitive Behavior Seminar and the satiating effect of cholecystokinin.

Synergism between the Columbia University Appetitive Behavior Seminar and the research program of Smith and Gibbs on the satiating effect of cholecystokinin during the past 40 years is described. The Seminar was synergistic with the research program in five ways. First, the steady parade of speakers gave us a window on the varied and interesting work going on in the field. Second, the Seminar was the kind of audience for presentations of the work-in-progress on CCK that scientists hope for and rarely find. Criticism by members of the Seminar was relentless and constructive, and ideas for further experiments or new ways to tackle problematic data poured forth. Third, members of the Seminar did experiments that facilitated the experimental success of the research program. Fourth, members of the Seminar tutored us on topics that we wanted to import into the research program on CCK. Fifth, and probably most important, members of the Seminar gave us the encouragement, good humor, and friendship so necessary for coping with the struggles of the scientific life.

Hippocampal neurons inhibit meal onset.

There is extensive research regarding the neural mechanisms involved in satiety and meal termination; in contrast, there is very limited understanding of how meal onset is regulated. On the basis of several converging lines of evidence, we hypothesized that hippocampal neurons form a memory of a meal and inhibit meal onset during the postprandial period. As a first step, we tested whether reversible inactivation of the hippocampus with muscimol infusions after the end of one meal would accelerate the onset of the next meal. To test this, adult male Sprague-Dawley rats (N = 23) were implanted with a cannula aimed at the right or left dorsal hippocampus and then trained to consume a 32% sucrose solution at a scheduled time daily. On the experimental day, hippocampal neuronal activity was temporarily disrupted during the postprandial period by infusing muscimol (0.5 µg/µl; 1 µl) 5 min after the rats stopped consuming the sucrose solution. Compared to vehicle infusions, muscimol infusions significantly decreased the latency to start the postinfusion meal and increased the size of the postinfusion meal. In addition, muscimol disrupted the relationship between the size of a meal and length of the following postprandial period. These effects of muscimol on meal onset were not due to an effect on the speed of consumption. Collectively, these findings are consistent with the hypothesis that hippocampal neurons suppress meal initiation during the postprandial period. Given that overeating can impair hippocampal function, these findings suggest that impaired hippocampal functioning is a cause and consequence of overeating and obesity.

Hervey, Harris, and the parabiotic search for lipostatic signals.

This paper is an introduction to the papers by Hervey and Harris that describe their experimental use of parabiosis in rats and mice to search for circulating lipostatic signals. Beginning in 1959 with Hervey's foundational paper, they detected three parabiotic signals: the Hervey signal decreases food intake and fat mass in rats; the antilipogenic factor (ALF) decreased fat mass, but not food intake in rats; and the leptin-dependent signal in lean partners of ob/ob mice decreased fat mass, but not food intake. The known lipostatic signals, leptin and insulin, have been candidates for the Hervey and ALF signals, but insulin has been excluded and the evidence for leptin is inconclusive. The site of production of the three parabiotic signals and their molecular structure are not known and specific mechanisms of their lipostatic control are incompletely understood. Given their potential importance for understanding the physiology of lipostatic controls and for developing new therapies for obesity, Hervey and Harris make a strong argument for further research on the three parabiotic signals.

Successful application of lead isotopes in source apportionment, legal proceedings, remediation and monitoring.

In late 2006, the seaside community in Esperance Western Australia was alerted to thousands of native bird species dying. The source of the lead (Pb) was determined by Pb isotopes to derive from the handling of Pb carbonate concentrate through the Port, which began in July 2005. Concern was expressed for the impact of this on the community. Our objectives were to employ Pb isotope ratios to evaluate the source of Pb in environmental samples for use in legal proceedings, and for use in remediation and monitoring. Isotope measurements were undertaken of bird livers, plants, drinking water, soil, harbour sediments, air, bulk ceiling dust, gutter sludge, surface swabs and blood. The unique lead isotopic signature of the contaminating Pb carbonate enabled diagnostic apportionment of lead in samples. Apart from some soil and water samples, the proportion of contaminating Pb was >95% in the environmental samples. Lead isotopes were critical in resolving legal proceedings, are being used in the remediation of premises, were used in monitoring of workers involved in the decontamination of the storage facility, and monitoring transport of the concentrate through another port facility. Air samples show the continued presence of contaminant Pb, more than one year after shipping of concentrate ceased, probably arising from dust resuspension. Brief details of the comprehensive testing and cleanup of the Esperance community are provided along with the role of the Community. Lead isotopic analyses can provide significant benefits to regulatory agencies, interested parties, and the community where the signature is able to be characterised with a high degree of certainty.