Airborne Lidar Measurements of XCO2 in Synoptically Active Environment and Associated Comparisons With Numerical Simulations.

Frontal boundaries have been shown to cause large changes in CO2 mole-fractions, but clouds and the complex vertical structure of fronts make these gradients difficult to observe. It remains unclear how the column average CO2 dry air mole-fraction (XCO2) changes spatially across fronts, and how well airborne lidar observations, data assimilation systems, and numerical models without assimilation capture XCO2 frontal contrasts (ΔXCO2, i.e., warm minus cold sector average of XCO2). We demonstrated the potential of airborne Multifunctional Fiber Laser Lidar (MFLL) measurements in heterogeneous weather conditions (i.e., frontal environment) to investigate the ΔXCO2 during four seasonal field campaigns of the Atmospheric Carbon and Transport-America (ACT-America) mission. Most frontal cases in summer (winter) reveal higher (lower) XCO2 in the warm (cold) sector than in the cold (warm) sector. During the transitional seasons (spring and fall), no clear signal in ΔXCO2 was observed. Intercomparison among the MFLL, assimilated fields from NASA's Global Modeling and Assimilation Office (GMAO), and simulations from the Weather Research and Forecasting--Chemistry (WRF-Chem) showed that (a) all products had a similar sign of ΔXCO2 though with different levels of agreement in ΔXCO2 magnitudes among seasons; (b) ΔXCO2 in summer decreases with altitude; and (c) significant challenges remain in observing and simulating XCO2 frontal contrasts. A linear regression analyses between ΔXCO2 for MFLL versus GMAO, and MFLL versus WRF-Chem for summer-2016 cases yielded a correlation coefficient of 0.95 and 0.88, respectively. The reported ΔXCO2 variability among four seasons provide guidance to the spatial structures of XCO2 transport errors in models and satellite measurements of XCO2 in synoptically-active weather systems.

Association of distal hyperintense vessel sign and recurrent stroke in patients with symptomatic intracranial stenosis.

OBJECTIVE: The distal hyperintense vessel sign (DHV) on fluid-attenuated inversion recovery magnetic resonance image (MRI) is an imaging biomarker of slow leptomeningeal collateral flow in the presence of large artery stenosis or occlusion reflecting impaired cerebral hemodynamics. In this study, we aim to investigate the significance of the DHV sign in patients with symptomatic ≥ 70% intracranial atherosclerotic stenosis. METHODS: We retrospectively reviewed patients with ischemic stroke or transient ischemic attack admitted to a single center from January 2010 to December 2017. Patients were included if they had symptomatic ≥ 70% atherosclerotic stenosis of the intracranial internal carotid artery or middle cerebral artery. The presence of the DHV sign was evaluated by blinded neuroradiologist and vascular neurologists. Recurrent ischemic stroke in the vascular territory of symptomatic intracranial artery was defined as new neurological deficits with associated neuroimaging findings during the follow up period. RESULTS: A total of 109 patients were included in the study, of which 55 had DHV sign. Average duration of follow up was 297 ± 326 days. Four patients were lost during follow up. Patients with the DHV sign had a higher rate of recurrent ischemic stroke (38%), compared to patients without the DHV sign (17%; p=0.018). In multivariate regression analysis, the presence of DHV sign was an independent predictor of recurrent ischemic stroke. A DHV score of ≥ 2 had a 63% sensitivity and 69% specificity for recurrent ischemic stroke. INTERPRETATION: In patients with severe symptomatic intracranial atherosclerotic stenosis, those with a DHV sign on MRI are at higher risk of recurrent ischemic stroke.

Professional Pitchers Display Differences in UCL Morphology and Elbow Gapping During Moving Valgus Stress Testing After UCL Reconstruction.

BACKGROUND: Ulnar collateral ligament (UCL) reconstruction (UCLR) of the elbow has received much attention given the rise in incidence among baseball pitchers. Stress ultrasonography has been demonstrated to be a critical evaluation tool of the UCL. No study has dynamically evaluated the ability of UCLR to restore normal kinematics. PURPOSE/HYPOTHESIS: The purpose of this study was to compare ulnohumeral gapping during a moving valgus stress test as well as UCL thickness between professional pitchers with and without UCLR. We hypothesized that the ulnohumeral joint will display greater gapping and the UCL graft will be thicker in pitchers after UCLR compared with uninjured pitchers. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Ultrasonography was used to measure the medial ulnohumeral joint distance and the UCL thickness of 70 asymptomatic professional baseball pitchers; 6 of the participants had a history of UCLR. Images were captured of the dominant (D) and nondominant (ND) elbows at the maximal cocking position under 2 loaded conditions within the moving valgus stress test arc: (1) gravity stress and (2) 2.5 kg (5.5 lb) of valgus force using a dynamometer. Intra- and interrater reliability of the measurements was established with intraclass correlation coefficients (ICCs). Separate mixed-model analyses of variance (D side × UCL) were used to compare the D and ND elbow variables between pitchers with and without a history of UCLR. RESULTS: All measurements displayed good reliability according to ICCs. Pitchers with a history of UCLR demonstrated less gapping (5.6 ± 2.9 vs 4.2 ± 1.2 mm; P = .002) and greater UCL graft thickness (0.17 ± 0.07 vs 0.11 ± 0.08 mm; P = .03) compared with the native ligament in pitchers without prior UCL injury. CONCLUSION: Our data demonstrated that the UCLR results in a thicker, stiffer construct with less medial elbow gapping than the anatomical UCL. Using ultrasound to evaluate the UCL was a reliable, efficient, and clinically feasible method to assess UCL thickness and joint gapping in players with a history of UCLR. Future studies may consider this approach to evaluate surgical techniques and graft types for UCLR.

Biomechanical evaluation of an intramedullary clavicle screw in simple oblique and butterfly wedge fractures.

This biomechanical study evaluates the performance of a solid titanium-alloy intra-medullary (IM) clavicular screw in torsion and cantilever bending in cadaveric clavicle specimens with simulated simple oblique and butterfly wedge midshaft fractures. Thirty-two fresh-frozen male clavicles were sorted into six experimental groups: Torsion Control, Torsion Simple Oblique Fracture, Torsion Butterfly Wedge Fracture, Bending Control, Bending Simple Oblique Fracture, and Bending Butterfly Wedge Fracture. The experimental groups were controlled for density, length, diameter, and laterality. All other samples were osteotomy-induced and implanted with a single 90 mm × 3 mm clavicle screw. All groups were tested to physiologically relevant cutoff points in torsion or bending. There were no statistically significant differences in the performance of the oblique and butterfly wedge fracture models for any torsion or bend testing measures, including maximum torsional resistance (p = 0.66), torsional stiffness (p = 0.51), maximum bending moment (p = 0.43), or bending stiffness (p = 0.73). Torsional testing of samples in the direction of thread tightening tended to be stronger than samples tested in loosening, with all groups either approaching or achieving statistical significance. There were no significant differences between the simple oblique or the butterfly-wedge fracture groups for any of the tested parameters, suggesting that there is no difference in the gross biomechanical properties of the bone-implant construct when the IM clavicle screw is used in either a simple midshaft fracture pattern or a more complex butterfly wedge fracture pattern.

Geographic variation in the treatment of proximal humerus fracture: an update on surgery rates and treatment consensus.

BACKGROUND: Using a larger, more comprehensive sample, and inclusion of the reverse shoulder arthroplasty as a primary surgical approach for proximal humerus fracture, we report on geographic variation in the treatment of proximal humerus fracture in 2011 and comment on whether treatment consensus is being reached. METHODS: This was a retrospective cohort study of Medicare patients with an x-ray-confirmed diagnosis of proximal humerus fracture in 2011. Patients receiving reverse shoulder arthroplasty, hemiarthroplasty, or open reduction internal fixation within 60 days of their diagnosis were classified as surgical management patients. Unadjusted observed surgery rates and area treatment ratios adjusted for patient demographic and clinical characteristics were calculated at the hospital referral region level. RESULTS: Among patients with proximal humerus fracture (N = 77,053), 15.4% received surgery and 84.6% received conservative management. Unadjusted surgery rates varied from 1.7 to 33.3% across hospital referral regions. Among patients receiving surgery, 22.3% received hemiarthroplasty, 65.8% received open reduction internal fixation, and 11.8% received reverse shoulder arthroplasty. Patients that were female, were younger, had fewer medical comorbidities, had a lower frailty index, were white, or were not dual-eligible for Medicaid during the month of their index fracture were more likely to receive surgery (p < .0001). Geographic variation in the treatment of proximal humerus fracture persisted after adjustment for patient demographic and clinical differences across local areas. Average surgery rates ranged from 9.9 to 21.2% across area treatment ratio quintiles. CONCLUSIONS: Persistent geographic variation in surgery rates for proximal humerus fracture across the USA suggests no treatment consensus has been reached.

Management of Three- and Four-Part Proximal Humerus Fractures.

The management of three- and four-part proximal humerus fractures remains controversial because the literature has supported all forms of management, including nonsurgical management, open reduction and internal fixation (ORIF), and shoulder arthroplasty. Specific patient factors ultimately influence the decision of which treatment best fits the patient and the fracture. Surgeons should understand the rationale for nonsurgical and surgical management of these fractures, including ORIF and reverse shoulder arthroplasty.

Is There a Preoperative Morphine Equianalgesic Dose that Predicts Ability to Achieve a Clinically Meaningful Improvement Following Spine Surgery?

BACKGROUND: Preoperative opioid use is widespread and associated with worse patient-reported outcomes following spine surgery. OBJECTIVE: To calculate a threshold preoperative morphine equianalgesic (MEA) dose beyond which patients are less likely to achieve the minimum clinically important difference (MCID) following elective surgery for degenerative spine disease. METHODS: The study included 543 cervical and 1293 lumbar patients. Neck Disability Index and Oswestry Disability Index scores were collected at baseline and 12 mo postoperatively. Preoperative MEA doses were calculated retrospectively. Multivariate logistic regression was then performed to determine the relationship between MEA dose and the odds of achieving MCID. As a part of this regression, Bayesian inference and Markov Chain Monte Carlo methods were used to estimate the values of inflection points (or "thresholds") in MEA. RESULTS: Overall, 1020 (55.5%) patients used preoperative opioids. A total of 50.3% of cervical and 61.9% of lumbar patients achieved MCID. The final logistic regression model demonstrated that MCID achievement decreased significantly when mean preoperative MEA dose exceeded 47.8 mg/d, with a 95% credible interval of 29.0 to 60.0 mg/d. CONCLUSION: Minimum and maximum MEA doses exist, between which increasing opioid dose is associated with decreased ability to achieve clinically meaningful improvement following spine surgery. Patients with preoperative MEA dose exceeding 29 mg/d, the lower limit of the 95% credible interval for the mean MEA dose above which patients exhibit significantly decreased achievement of MCID, may be considered for preoperative opioid weaning.

Atmospheric CO(2) column measurements in cloudy conditions using intensity-modulated continuous-wave lidar at 1.57 micron.

This study evaluates the capability of atmospheric CO2 column measurements under cloudy conditions using an airborne intensity-modulated continuous-wave integrated-path-differential-absorption lidar operating in the 1.57-µm CO2 absorption band. The atmospheric CO2 column amounts from the aircraft to the tops of optically thick cumulus clouds and to the surface in the presence of optically thin clouds are retrieved from lidar data obtained during the summer 2011 and spring 2013 flight campaigns, respectively. For the case of intervening thin cirrus clouds with an average cloud optical depth of about 0.16 over an arid/semi-arid area, the CO2 column measurements from 12.2 km altitude were found to be consistent with the cloud free conditions with a lower precision due to the additional optical attenuation of the thin clouds. The clear sky precision for this flight campaign case was about 0.72% for a 0.1-s integration, which was close to previously reported flight campaign results. For a vegetated area and lidar path lengths of 8 to 12 km, the precision of the measured differential absorption optical depths to the surface was 1.3 - 2.2% for 0.1-s integration. The precision of the CO2 column measurements to thick clouds with reflectance about 1/10 of that of the surface was about a factor of 2 to 3 lower than that to the surface owing to weaker lidar returns from clouds and a smaller CO2 differential absorption optical depth compared to that for the entire column.

Super-resolution technique for CW lidar using Fourier transform reordering and Richardson-Lucy deconvolution.

An interpolation method is described for range measurements of high precision altimetry with repeating intensity modulated continuous wave (IM-CW) lidar waveforms using binary phase shift keying (BPSK), where the range profile is determined by means of a cross-correlation between the digital form of the transmitted signal and the digitized return signal collected by the lidar receiver. This method uses reordering of the array elements in the frequency domain to convert a repeating synthetic pulse signal to single highly interpolated pulse. This is then enhanced further using Richardson-Lucy deconvolution to greatly enhance the resolution of the pulse. We show the sampling resolution and pulse width can be enhanced by about two orders of magnitude using the signal processing algorithms presented, thus breaking the fundamental resolution limit for BPSK modulation of a particular bandwidth and bit rate. We demonstrate the usefulness of this technique for determining cloud and tree canopy thicknesses far beyond this fundamental limit in a lidar not designed for this purpose.

High-resolution CW lidar altimetry using repeating intensity-modulated waveforms and Fourier transform reordering.

An interpolation method is described for range measurements of high precision and altimetry using repeating intensity-modulated continuous wave (IM-CW) lidar waveforms, where the range is determined by means of a cross-correlation between the digital form of the transmitted signal and the digitized return signal collected by the lidar receiver. This method uses reordering of the array elements in the frequency domain to convert a repeating synthetic pulse signal to single highly interpolated pulse. The computation of this processing is marginally greater than the correlation itself, as it only involves reordering of the correlation in the frequency domain, which makes it possible to implement this in a real time application. It is shown through theoretical arguments and flight-testing that this is a viable method for high-speed interpolated range measurements. Standard deviation is 0.75 m over water with only 350 mw of transmitted power at 2600 m.

Advanced sine wave modulation of continuous wave laser system for atmospheric CO(2) differential absorption measurements.

In this theoretical study, modulation techniques are developed to support the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. A continuous wave (CW) lidar system using sine waves modulated by maximum length (ML) pseudo-noise (PN) codes is described for making simultaneous online/offline differential absorption measurements. Amplitude and phase-shift keying (PSK) modulated intensity modulation (IM) carriers, in addition to a hybrid-pulse technique are investigated, which exhibit optimal autocorrelation properties. A method is presented to bandwidth limit the ML sequence based on a filter implemented in terms of Jacobi theta functions, which does not significantly degrade the resolution or introduce sidelobes as a means of reducing aliasing and IM carrier bandwidth.

Salvage of contaminated osteochondral allografts: the effects of chlorhexidine on human articular chondrocyte viability.

BACKGROUND: Because chondrocyte viability is imperative for successful osteochondral allograft transplantation, sterilization techniques must provide antimicrobial effects with minimal cartilage toxicity. Chlorhexidine gluconate (CHG) is an effective disinfectant; however, its use with human articular cartilage requires further investigation. PURPOSE: To determine the maximal chlorhexidine concentration that does not affect chondrocyte viability in allografts and to determine whether this concentration effectively sterilizes contaminated osteoarticular grafts. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral plugs were subjected to pulse lavage with 1-L solutions of 0.002%, 0.01%, 0.05%, and 0.25% CHG and cultured for 0, 1, 2, and 7 days in media of 10% fetal bovine serum and antibiotics. Chondrocyte viability was determined via LIVE/DEAD Viability Assay. Plugs were contaminated with Staphylococcus aureus and randomized to 4 treatment groups. One group was not contaminated; the 3 others were contaminated and received no treatment, saline pulse lavage, or saline pulse lavage with 0.002% CHG. Serial dilutions were plated and colony-forming units assessed. RESULTS: The control group and the 0.002% CHG group showed similar cell viability, ranging from 67% ± 4% to 81% ± 22% (mean ± SD) at all time points. In the 0.01% CHG group, cell viability was reduced in comparison with control by 2-fold at day 2 and remained until day 7 (P < .01). The 0.05% and 0.25% CHG groups showed a 2-fold reduction in cell viability at day 1 (P < .01). At day 7, cell viability was reduced to 15% ± 18% (4-fold decrease) for the 0.05% CHG group and 10% ± 19% (6-fold decrease) for the 0.25% CHG group (P < .01). Contaminated grafts treated with 0.002% CHG demonstrated no colony-forming units. CONCLUSION: Pulse lavage with 0.002% CHG does not cause significant cell death within 7 days after exposure, while CHG at concentrations >0.002% significantly decreases chondrocyte viability within 1 to 2 days after exposure and should therefore not be used for disinfection of osteochondral allograft. Pulse lavage does not affect chondrocyte viability but cannot be used in isolation to sterilize contaminated fragments. Overall, 0.002% CHG was shown to effectively decontaminate osteoarticular fragments. CLINICAL RELEVANCE: This study offers a scientific protocol for sterilizing osteochondral fragments that does not adversely affect cartilage viability.

Binary phase shift keying on orthogonal carriers for multi-channel CO2 absorption measurements in the presence of thin clouds.

A new modulation technique for Continuous Wave (CW) Lidar is presented based on Binary Phase Shift Keying (BPSK) using orthogonal carriers closely spaced in frequency, modulated by Maximum Length (ML) sequences, which have a theoretical autocorrelation function with no sidelobes. This makes it possible to conduct multi-channel atmospheric differential absorption measurements in the presence of thin clouds without the need for further processing to remove errors caused by sidelobe interference while sharing the same modulation bandwidth. Flight tests were performed and data were collected using both BPSK and linear swept frequency modulation. This research shows there is minimal or no sidelobe interference in the presence of thin clouds for BPSK compared to linear swept frequency with significant sidelobe levels. Comparisons between of CO(2) optical depth Signal to Noise (SNR) between the BPSK and linear swept frequency cases indicate a 21% drop in SNR for BPSK experimentally using the instrument under consideration.

Nonlinear swept frequency technique for CO2 measurements using a CW laser system.

A system using a nonlinear multiswept sine wave is described, which employs multichannel multiswept orthogonal waves, to separate channels and make multiple, simultaneous online/offline CO(2) measurements. An analytic expression and systematic method for determining the orthogonal frequencies for the unswept, linear swept, and nonlinear swept cases is presented. It is shown that one may reduce sidelobes of the autocorrelation function while preserving cross channel orthogonality, for thin cloud rejection.

Endostatin binds nerve growth factor and thereby inhibits neurite outgrowth and neuronal migration in-vitro.

Endostatin (ES), the C-terminal fragment of collagen XVIII known for its anti-angiogenic properties, is associated with neurological diseases in mammals. In this study, we investigated the effect of ES on nerve growth factor (NGF)-induced neuronal differentiation, migration, neuritogenesis, and neurite extension. ES partially inhibited PC12 cell differentiation and cerebellar granule cell migration. In addition, neurite outgrowth was inhibited in a concentration-dependent manner. This effect was also matrix-dependent, as we observed better inhibition on PC12 cells grown on collagen compared to laminin matrices. Furthermore, we observed partial NGF depletion by collagen and ES, but not by laminin suggesting that NGF-matrix interactions may be important for promoting neuritogenesis, competitive inhibition by ES or low affinity matrix impairs PC12 differentiation and neurite outgrowth. Finally, using a biosensor technique, we demonstrated a direct interaction between NGF and ES suggesting the mechanism of action of ES may involve NGF sequestration. In conclusion, our study demonstrates the inhibitory effect of ES on different steps of neurogenesis including cell differentiation and migration and neuritogenesis by NGF sequestration. Such sequestration may compromise brain repair following injury, but also may play important role in axon finding as well as a potent therapeutical target in diseases involving abnormal elevated neurotrophic growth factor levels. Taken together, this study raises the consideration of ES as a double-edge sword that carries both deleterious and putative therapeutical effects.

Synthetic quadrature phase detector/demodulator for Fourier transform spectrometers.

A method is developed to demodulate (velocity correct) Fourier transform spectrometer data that are taken with an analog to digital converter that digitizes equally spaced in time. This method makes it possible to use simple low-cost, high-resolution audio digitizers to record high-quality data without the need for an event timer or quadrature laser hardware and makes it possible to use a metrology laser of any wavelength. The reduced parts count and simple implementation make it an attractive alternative in space-based applications when compared to previous methods such as the Brault algorithm.

Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans.

CONTEXT: Genetic variation at the transcription factor 7-like 2 locus has been linked to type 2 diabetes in predominantly European-derived populations. The biological basis of these associations remains to be determined. OBJECTIVE: The objective of this study was to evaluate previously associated variants for association with measures of glucose homeostasis in Hispanic-Americans and African-Americans and determine the biological mechanism(s) through which these variants exert their effect. DESIGN: This study was the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). SETTING: The IRAS-FS is a community-based study of Hispanic-Americans (San Antonio, TX, and San Luis Valley, CO) and African-Americans (Los Angeles, CA). PARTICIPANTS: A total of 1040 Hispanic-American and 500 African-American individuals from the IRAS-FS formed the basis of this study. MAIN OUTCOMES MEASURES(S): The primary glucose homeostasis phenotypes of interest in this study were derived from the frequently sampled iv glucose tolerance test and include insulin sensitivity, acute insulin response, and disposition index. RESULTS: In Hispanic-Americans, significant evidence of association was observed between single-nucleotide polymorphisms rs7903146 and rs112255372 with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (P = 0.032 and 0.036, respectively). Other quantitative measures, e.g. insulin sensitivity or disposition index, were not associated with the single nucleotide polymorphisms examined. In African-Americans there was no evidence of association observed. CONCLUSIONS: These results suggest that transcription factor 7-like 2 variants could play a role in the pathogenesis of type 2 diabetes in the Hispanic-American population through a mechanism involving insulin secretion.

The SMM model as a boundary value problem using the discrete diffusion equation.

A generalized single-step stepwise mutation model (SMM) is developed that takes into account an arbitrary initial state to a certain partial difference equation. This is solved in both the approximate continuum limit and the more exact discrete form. A time evolution model is developed for Y DNA or mtDNA that takes into account the reflective boundary modeling minimum microsatellite length and the original difference equation. A comparison is made between the more widely known continuum Gaussian model and a discrete model, which is based on modified Bessel functions of the first kind. A correction is made to the SMM model for the probability that two individuals are related that takes into account a reflecting boundary modeling minimum microsatellite length. This method is generalized to take into account the general n-step model and exact solutions are found. A new model is proposed for the step distribution.

Association of the estrogen receptor-alpha gene with the metabolic syndrome and its component traits in African-American families: the Insulin Resistance Atherosclerosis Family Study.

OBJECTIVE: We previously detected an association between a region of the estrogen receptor-alpha (ESR1) gene and type 2 diabetes in an African-American case-control study; thus, we investigated this region for associations with the metabolic syndrome and its component traits in African-American families from the Insulin Resistance Atherosclerosis Family Study. RESEARCH DESIGN AND METHODS: A total of 17 single nucleotide polymorphisms (SNPs) from a contiguous 41-kb intron 1-intron 2 region of the ESR1 gene were genotyped in 548 individuals from 42 African-American pedigrees. Generalized estimating equations were computed using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation. RESULTS: Significant associations were detected between ESR1 SNPs and the metabolic syndrome (P = 0.005 to P = 0.029), type 2 diabetes (P = 0.001), insulin sensitivity (P = 0.0005 to P = 0.023), fasting insulin (P = 0.022 to P = 0.033), triglycerides (P = 0.021), LDL (P = 0.016 to P = 0.034), cholesterol (P = 0.046), BMI (P = 0.016 to P = 0.035), waist circumference (P = 0.012 to P = 0.023), and subcutaneous adipose tissue area (P = 0.016). CONCLUSIONS: It appears likely that ESR1 contributes to type 2 diabetes and CVD risk via pleiotropic effects, leading to insulin resistance, a poor lipid profile, and obesity.

Genetic mapping of disposition index and acute insulin response loci on chromosome 11q. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study.

Glucose homeostasis, a defining characteristic of physiological glucose metabolism, is the result of complex feedback relationships with both genetic and environmental determinants that influence insulin sensitivity and beta-cell function. Relatively little is known about the genetic basis of glucose homeostasis phenotypes or their relationship to risk of diabetes. Our group previously published a genome scan for glucose homeostasis traits in 284 African-American subjects from 21 pedigrees in the Insulin Resistance Atherosclerosis Study Family Study (IRASFS) and presented evidence for linkage to disposition index (DI) on chromosome 11q with a logarithm of odds (LOD) of 3.21 at 81 cM flanked by markers D11S2371 and D11S2002 (support interval from 71 to 96 cM). In this study, genotyping and analysis of an additional 214 African-American subjects in 21 pedigrees from the IRASFS yielded independent evidence of linkage to DI. When these two datasets were combined, a DI linkage peak was observed with an LOD of 3.89 at 78 cM (support interval from 67 to 89 cM). Fine mapping with 15 additional microsatellite markers in this 11q region for the entire 42 pedigrees resulted in an LOD score of 4.80 at 80 cM near marker D11S937 (support interval from 76 to 84 cM). In these 42 pedigrees, there was also suggestive evidence for linkage to acute insulin response (AIR) at two separate locations flanking the DI peak (64 cM, LOD 2.77, flanked by markers D11S4076 and D11S981; and 85 cM, LOD 2.54, flanked by markers D11S4172 and D11S2002). No evidence of linkage to the insulin sensitivity index (S(i)) was observed. Nine positional candidate genes were evaluated for association to DI and AIR. Among these candidates, single nucleotide polymorphisms (SNPs) in muscle glycogen phosphorylase showed evidence of association with DI (P < 0.011). In addition, SNPs in the pyruvate carboxylase gene showed evidence of association (P < 0.002) with AIR. Further analysis of these candidate genes, however, did not provide evidence that these SNPs accounted for the evidence of linkage to either DI or AIR. These detailed genetic analyses provide strong evidence of a DI locus on 11q in African-American pedigrees, with additional suggestive evidence of independent AIR loci in the same region.