Rapid grain boundary diffusion in foraminifera tests biases paleotemperature records.

The oxygen isotopic compositions of fossil foraminifera tests constitute a continuous proxy record of deep-ocean and sea-surface temperatures spanning the last 120 million years. Here, by incubating foraminifera tests in 18O-enriched artificial seawater analogues, we demonstrate that the oxygen isotopic composition of optically translucent, i.e., glassy, fossil foraminifera calcite tests can be measurably altered at low temperatures through rapid oxygen grain-boundary diffusion without any visible ultrastructural changes. Oxygen grain boundary diffusion occurs sufficiently fast in foraminifera tests that, under normal upper oceanic sediment conditions, their grain boundaries will be in oxygen isotopic equilibrium with the surrounding pore fluids on a time scale of <100 years, resulting in a notable but correctable bias of the paleotemperature record. When applied to paleotemperatures from 38,400 foraminifera tests used in paleoclimate reconstructions, grain boundary diffusion can be shown to bias prior paleotemperature estimates by as much as +0.86 to -0.46 °C. The process is general and grain boundary diffusion corrections can be applied to other polycrystalline biocarbonates composed of small nanocrystallites (<100 nm), such as those produced by corals, brachiopods, belemnites, and molluscs, the fossils of which are all highly susceptible to the effects of grain boundary diffusion.

Fast and pervasive diagenetic isotope exchange in foraminifera tests is species-dependent.

Oxygen isotope compositions of fossil foraminifera tests are commonly used proxies for ocean paleotemperatures, with reconstructions spanning the last 112 million years. However, the isotopic composition of these calcitic tests can be substantially altered during diagenesis without discernible textural changes. Here, we investigate fluid-mediated isotopic exchange in pristine tests of three modern benthic foraminifera species (Ammonia sp., Haynesina germanica, and Amphistegina lessonii) following immersion into an 18O-enriched artificial seawater at 90 °C for hours to days. Reacted tests remain texturally pristine but their bulk oxygen isotope compositions reveal rapid and species-dependent isotopic exchange with the water. NanoSIMS imaging reveals the 3-dimensional intra-test distributions of 18O-enrichment that correlates with test ultra-structure and associated organic matter. Image analysis is used to quantify species level differences in test ultrastructure, which explains the observed species-dependent rates of isotopic exchange. Consequently, even tests considered texturally pristine for paleo-climatic reconstruction purposes may have experienced substantial isotopic exchange; critical paleo-temperature record re-examination is warranted.

Facies and depositional environments of the Upper Muschelkalk (Schinznach Formation, Middle Triassic) in northern Switzerland.

Subsurface sedimentary strata in northern Switzerland, such as the Middle Triassic Upper Muschelkalk, are attracting interest as potential reservoirs for CO2 sequestration and for geothermal energy production. Characterizing facies in such strata aids prediction of reservoir properties in unexplored areas. Although well studied elsewhere, the Swiss Upper Muschelkalk has received little attention despite containing the southern-most deposits of the Central European Basin. The Upper Muschelkalk represents the deposits of a storm-dominated, homoclinal carbonate ramp, developed during a basin-wide 3rd-order transgressive-regressive cycle. Our facies analyses of nine boreholes across northern Switzerland reveal 12 lithofacies, eight lithofacies associations and four types of metre-scale 5th-order cycles corresponding to at least 23 short orbital eccentricity cycles. During the 3rd-order transgression, crinoidal bioherms developed across Switzerland followed by deep-ramp environments. Subsequently, tempestites were deposited up to and after the basin-wide maximum flooding surface. Lateral tempestite correlations indicate that Switzerland lay within an open-marine, mid-ramp environment during almost half of the depositional history. Mid-ramp deposits pass upwards to prograding shelly shoals, which sheltered a back-shoal lagoon containing patchy oolitic shoals. At the top of the Upper Muschelkalk, back-shoal sediments give way to coastal sabkha facies, which were overlain by oolitic shoals during a marine transgression. Shortly thereafter the top of the Upper Muschelkalk was dolomitized by brines from an overlying hypersaline environment that was later removed by a basin-wide erosive event. Overall, the paucity of porous shoal facies, unlike in southern Germany, has resulted in poor primary reservoir properties in the Upper Muschelkalk of Switzerland.

Cardiac Valve Annulus Diameters in Extremely Preterm Infants: A Cross-Sectional Echocardiographic Study.

BACKGROUND: With the increasing incidence of births of very preterm very-low-birth-weight infants, there is a demand for echocardiographic reference values of cardiac dimensions. OBJECTIVES: The aim of this study was to provide reference values of cardiac valve annulus diameters in a cohort of extremely preterm very-low-birth-weight neonates and to correlate these with patient characteristics. METHODS: Valve diameters of 376 infants of < 32 weeks' gestation and with a birth weight of ≤2,000 g were measured using 2-dimensional echocardiography. Correlations between valve diameters and patient characteristics (birth length/weight, body surface area, gestational age, and sex) were assessed. Birth weight was used to establish linear regression models. Inter- and intraobserver agreement was assessed through intraclass correlation coefficient (ICC) analysis. RESULTS: Substantial variability was found (aortic valve mean [standard deviation; range]: 5.0 mm [0.6; 3.7-6.5]; pulmonic valve: 5.8 mm [0.8; 3.4-7.9]; mitral valve: 8.0 mm [1.0; 5.5-10.5]; tricuspid valve: 7.6 mm [1.2; 4.9-10.6]). There was a moderate correlation between birth weight and valve diameter (R2 aortic valve: 0.36; pulmonic valve: 0.20; mitral valve: 0.24; tricuspid valve: 0.24). Adequate intraobserver (ICC range 0.74-0.91) and interobserver agreement (ICC range 0.77-0.89) was found. CONCLUSIONS: Our study provides ready-to-use reference values for cardiac valve annulus diameters for extremely preterm infants.

Tumor-Specific Uptake of Fluorescent Bevacizumab-IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study.

Purpose: To provide proof of principle of safety, breast tumor-specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW targeting VEGF-A in patients with breast cancer.Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.Results: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level.Conclusions: Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. Clin Cancer Res; 23(11); 2730-41. ©2016 AACR.

Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in Human Breast Cancer.

In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and nonmalignant tissues are usually distinguished on fluorescence images by applying empirically determined fluorescence intensity thresholds. Here, we report the development of fSTREAM, a set of analytic methods designed to streamline the analysis of surgically excised breast tissues by collecting and statistically processing hybrid multiscale fluorescence, color, and histology readouts toward precision fluorescence imaging. fSTREAM addresses core questions of how to relate fluorescence intensity to tumor tissue and how to quantitatively assign a normalized threshold that sufficiently differentiates tumor tissue from healthy tissue. Using fSTREAM we assessed human breast tumors stained in vivo with fluorescent bevacizumab at microdose levels. Showing that detection of such levels is achievable, we validated fSTREAM for high-resolution mapping of the spatial pattern of labeled antibody and its relation to the underlying cancer pathophysiology and tumor border on a per patient basis. We demonstrated a 98% sensitivity and 79% specificity when using labeled bevacizumab to outline the tumor mass. Overall, our results illustrate a quantitative approach to relate fluorescence signals to malignant tissues and improve the theranostic application of fluorescence molecular imaging. Cancer Res; 77(3); 623-31. ©2016 AACR.

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer.

PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS). RESULTS: Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3 ± 0.6, compared to a TNR of 1.4 ± 0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8 ± 0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0 ± 1.1 %I.D./g in DCIS + CAIX tumors, 4.6 ± 0.8 %I.D./g in DCIS tumors, while 2.0 ± 0.2 %I.D./g was obtained with R2-IR. CONCLUSIONS: These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

Imaging features of HER2 overexpression in breast cancer: a systematic review and meta-analysis.

Breast cancer imaging phenotype is diverse and may relate to molecular alterations driving cancer behavior. We systematically reviewed and meta-analyzed relations between breast cancer imaging features and human epidermal growth factor receptor type 2 (HER2) overexpression as a marker of breast cancer aggressiveness. MEDLINE and EMBASE were searched for mammography, breast ultrasound, magnetic resonance imaging (MRI), and/or [(18)F]fluorodeoxyglucose positron emission tomography studies through February 2013. Of 68 imaging features that could be pooled (85 articles, 23,255 cancers; random-effects meta-analysis), 11 significantly related to HER2 overexpression. Results based on five or more studies and robustness in subgroup analyses were as follows: the presence of microcalcifications on mammography [pooled odds ratio (pOR), 3.14; 95% confidence interval (CI), 2.46-4.00] or ultrasound (mass-associated pOR, 2.95; 95% CI, 2.34-3.71), branching or fine linear microcalcifications (pOR, 2.11; 95% CI, 1.07-4.14) or extremely dense breasts on mammography (pOR, 1.37; 95% CI, 1.07-1.76), and washout (pOR, 1.57; 95% CI, 1.11-2.21) or fast initial kinetics (pOR, 2.60; 95% CI, 1.43-4.73) on MRI all increased the chance of HER2 overexpression. Maximum [(18)F]fluorodeoxyglucose standardized uptake value (SUVmax) was higher upon HER2 overexpression (pooled mean difference, +0.76; 95% CI, 0.10-1.42). These results show that several imaging features relate to HER2 overexpression, lending credibility to the hypothesis that imaging phenotype reflects cancer behavior. This implies prognostic relevance, which is especially relevant as imaging is readily available during diagnostic work-up.

Cardiac magnetic resonance imaging findings and the risk of cardiovascular events in patients with recent myocardial infarction or suspected or known coronary artery disease: a systematic review of prognostic studies.

The goal of this study was to review the prognostic value of cardiac magnetic resonance (CMR) imaging findings for future cardiovascular events in patients with a recent myocardial infarction (MI) and patients with suspected or known coronary artery disease (CAD). Although the diagnostic value of CMR findings is established, the independent prognostic association with future cardiovascular events remains largely unclear. Studies published by February 2013, identified by systematic MEDLINE and EMBASE searches, were reviewed for associations between CMR findings (left ventricular ejection fraction [LVEF], wall motion abnormalities [WMA], abnormal myocardial perfusion, microvascular obstruction, late gadolinium enhancement, edema, and intramyocardial hemorrhage) and hard events (all-cause mortality, cardiac death, cardiac transplantation, and MI) or major adverse cardiovascular events (MACE) (hard events and other cardiovascular events defined by the authors of the evaluated papers). Fifty-six studies (n = 25,497) were evaluated. For patients with recent MI, too few patients were evaluated to establish associations between CMR findings and hard events. LVEF (range of adjusted hazard ratios [HRs]: 1.03 to 1.05 per % decrease) was independently associated with MACE. In patients with suspected or known CAD, WMA (adjusted HRs: 1.87 to 2.99), inducible perfusion defects (adjusted HRs: 3.02 to 7.77), LVEF (adjusted HRs: 0.72 to 0.82 per 10% increase), and infarction (adjusted HRs: 2.82 to 9.43) were independently associated with hard events, and the presence of inducible perfusion defects was associated with MACE (adjusted HRs: 1.76 to 3.21). The independent predictor of future cardiovascular events for patients with a recent MI was LVEF, and the predictors for patients with suspected or known CAD were WMA, inducible perfusion defects, LVEF, and presence of infarction.

The potential of hypoxia markers as target for breast molecular imaging--a systematic review and meta-analysis of human marker expression.

BACKGROUND: Molecular imaging of breast cancer is a promising emerging technology, potentially able to improve clinical care. Valid imaging targets for molecular imaging tracer development are membrane-bound hypoxia-related proteins, expressed when tumor growth outpaces neo-angiogenesis. We performed a systematic literature review and meta-analysis of such hypoxia marker expression rates in human breast cancer to evaluate their potential as clinically relevant molecular imaging targets. METHODS: We searched MEDLINE and EMBASE for articles describing membrane-bound proteins that are related to hypoxia inducible factor 1α (HIF-1α), the key regulator of the hypoxia response. We extracted expression rates of carbonic anhydrase-IX (CAIX), glucose transporter-1 (GLUT1), C-X-C chemokine receptor type-4 (CXCR4), or insulin-like growth factor-1 receptor (IGF1R) in human breast disease, evaluated by immunohistochemistry. We pooled study results using random-effects models and applied meta-regression to identify associations with clinicopathological variables. RESULTS: Of 1,705 identified articles, 117 matched our selection criteria, totaling 30,216 immunohistochemistry results. We found substantial between-study variability in expression rates. Invasive cancer showed pooled expression rates of 35% for CAIX (95% confidence interval (CI): 26-46%), 51% for GLUT1 (CI: 40-61%), 46% for CXCR4 (CI: 33-59%), and 46% for IGF1R (CI: 35-70%). Expression rates increased with tumor grade for GLUT1, CAIX, and CXCR4 (all p < 0.001), but decreased for IGF1R (p < 0.001). GLUT1 showed the highest expression rate in grade III cancers with 58% (45-69%). CXCR4 showed the highest expression rate in small T1 tumors with 48% (CI: 28-69%), but associations with size were only significant for CAIX (p < 0.001; positive association) and IGF1R (p = 0.047; negative association). Although based on few studies, CAIX, GLUT1, and CXCR4 showed profound lower expression rates in normal breast tissue and benign breast disease (p < 0.001), and high rates in carcinoma in situ. Invasive lobular carcinoma consistently showed lower expression rates (p < 0.001). CONCLUSIONS: Our results support the potential of hypoxia-related markers as breast cancer molecular imaging targets. Although specificity is promising, combining targets would be necessary for optimal sensitivity. These data could help guide the choice of imaging targets for tracer development depending on the envisioned clinical application.

Molecular imaging with a fluorescent antibody targeting carbonic anhydrase IX can successfully detect hypoxic ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is difficult to remove completely during surgery as it is not palpable and can therefore require re-excision. Real-time visualization of DCIS using near-infrared fluorescent probes could help the surgeon during surgery as well as the pathologist post-operatively to distinguish the tumor from healthy tissue. As hypoxia-induced necrosis is a common phenomenon in DCIS, we investigated the molecular imaging of DCIS using a fluorescent antibody targeting a hypoxia marker, carbonic anhydrase IX (CAIX), in a preclinical mouse model. A monoclonal antibody against human CAIX was fluorescently labeled with the near-infrared dye IRDye800CW and characterized in vitro. An in vivo study was performed in SCID/Beige mice that were orthotopically transplanted with human breast cancer cells mimicking human DCIS (MCF10DCIS) and MCF10DCIS stably expressing CAIX. A clinically approved fluorescence imaging system was used to monitor probe uptake and to determine tumor-to-normal tissue ratios (TNR). Mean in vivo TNR of CAIX-transduced (CAIX+) tumors was 7.5 ± 0.5. Mean in vivo TNR of DCIS tumors with hypoxic areas reached a plateau level at 48 h after injection of 2.1 ± 0.1 (mean ± SEM) compared to 1.7 ± 0.1 in DCIS without hypoxic areas. Mean intra-operative TNR of DCIS tumors with necrotic regions was higher than that of DCIS tumors without necrotic regions 96 h after injection-2.9 ± 0.1 and 1.5 ± 0.1, respectively-while the TNR of CAIX+ tumors was 11.2 ± 1.0. Specific tumor uptake of MabCAIX-IRDye800CW was confirmed by a biodistribution assay, and immunofluorescence imaging on tumor sections showed specific uptake in hypoxic tumor regions, with higher contrast than conventional chromagen-based immunohistochemistry. Molecular fluorescence imaging with MabCAIX-IRDye800CW can be successfully used to detect hypoxic DCIS before and during surgery to facilitate radical resection. Furthermore, it allows for sensitive CAIX-specific immunofluorescence microscopy of tumor sections, thereby introducing the concept of molecular fluorescence pathology.

Changes in the athletic profile of elite college American football players.

The purpose of this study was to compare positional anthropometric and National Football League (NFL) Combine performance levels in elite college American football players over the 3-year period from 1999 to 2001 to the 3-year period from 2008 to 2010. The sample included 15 offensive and defensive positions, and only those players invited to the combine and subsequently drafted in the same year (n = 1,712) were included in the study. Data from 10 combine physical tests were examined, including weight; height; the 9.1-, 18.3-, and 36.6-m sprints; the vertical and horizontal jumps; the 18.3-m shuttle run; the 3-cone drill; and the 102.1-kg bench press for maximum repetitions. Independent samples t-tests detected differences for each of the 15 positions (p < 0.05). There were no discernible trends in height and weight over the period in question, whereas players in the more recent group significantly improved performance in straight sprinting, the 3-cone drill, and the horizontal jump. Findings suggest that these tests better reflect characteristics such as explosiveness and first-step quickness as compared with the 18.3-m shuttle and the vertical jump, and that such characteristics have become more highly sought after by NFL coaches and scouts. The results of the present research suggest that the position-specific profiles changed over a relatively short period of time. Coaches and practitioners will be able to use the findings of this research to better prepare athletes for entry into the NFL.

Near-infrared fluorescence molecular imaging of ductal carcinoma in situ with CD44v6-specific antibodies in mice: a preclinical study.

PURPOSE: The purpose of this study was to develop a molecular imaging technique using tracers specific for ductal carcinoma in situ (DCIS) to improve visualization and localization of DCIS during surgery. As CD44v6 is frequently expressed in DCIS, we used near-infrared fluorescently labeled CD44v6-targeting antibodies for detection of DCIS. PROCEDURE: Mice bearing orthotopically transplanted CD44v6-positive MCF10DCIS DCIS-like tumors and CD44v6-negative MDA-MB-231 control tumors were intravenously injected with IRDye800CW conjugated to CD44v6-specific antibodies or control IgGs. Noninvasive imaging was performed for 8 days postinjection, followed by intraoperative imaging. Antibody accumulation and intratumor distribution were examined. RESULTS: Maximum accumulation of CD44v6-specific antibodies was obtained 24 h postinjection. Maximum tumor-to-background ratio for MCF10DCIS tumors was 4.5 ± 0.2, compared to 1.4 ± 0.1 (control tumors, p = 0.006), and 1.7 ± 0.1 (control IgG, p = 0.014), for 8 days postinjection. Ex vivo, tumor-to-background ratios were comparable to those obtained by intraoperative imaging. CONCLUSIONS: We show the applicability of noninvasive and intraoperative optical imaging of DCIS-like lesions in vivo using CD44v6-specific antibodies.

Mono- and multimodal registration of optical breast images.

Optical breast imaging offers the possibility of noninvasive, low cost, and high sensitivity imaging of breast cancers. Poor spatial resolution and a lack of anatomical landmarks in optical images of the breast make interpretation difficult and motivate registration and fusion of these data with subsequent optical images and other breast imaging modalities. Methods used for registration and fusion of optical breast images are reviewed. Imaging concerns relevant to the registration problem are first highlighted, followed by a focus on both monomodal and multimodal registration of optical breast imaging. Where relevant, methods pertaining to other imaging modalities or imaged anatomies are presented. The multimodal registration discussion concerns digital x-ray mammography, ultrasound, magnetic resonance imaging, and positron emission tomography.

Estimation of detection limits of a clinical fluorescence optical mammography system for the near-infrared fluorophore IRDye800CW: phantom experiments.

To evaluate if clinical fluorescence imaging of IRDye800CW is feasible on our fluorescence optical mammography system by estimating detection limits assessed by breast-cancer-simulating phantom experiments. Phantoms (2.1 cm(3), 0.9 cm(3)) with IRDye800CW concentrations of 0.5 to 120 nM were suspended in a 550 cm(3) measurement cup containing 507 surface-mounted source and detector fibers. The cup was filled with optical matching fluid containing IRDye800CW concentrations of 0, 5, 10, or 20 nM. Tomographic fluorescence images were acquired by exciting IRDye800CW at 730 nm; wavelengths above 750 nm were filtered. Signal intensities were calculated over a volume of interest corresponding to the size and location of the phantom in the reconstructed images. Correlations (R(2)) were calculated, and detection limits with associated upper 95% prediction interval were estimated. Between-day reproducibility was assessed with intraclass correlation coefficients (ICC). Fluorescent intensities were strongly correlated with phantom IRDye800CW concentrations (R(2)0.983 to 0.999). IRDye800CW detection limits ranged from 0.14 to 2.46 nM (upper 95% prediction limit 4.63 to 18.63 nM). ICC ranged from 0.88 to 1.00. The estimated detection limits for IRDye800CW were in the low-nanomolar range. These results support the start of clinical trials to evaluate the fluorescence optical mammography system using IRDye800CW labeled breast cancer targeting ligands.

The NFL combine: does it predict performance in the National Football League?

The authors investigate the correlation between National Football League (NFL) combine test results and NFL success for players drafted at three different offensive positions (quarterback, running back, and wide receiver) during a recent 6-year period, 1999-2004. The combine consists of series of drills, exercises, interviews, aptitude tests, and physical exams designed to assess the skills of promising college football players and to predict their performance in the NFL. Combine measures examined in this study include 10-, 20-, and 40-yard dashes, bench press, vertical jump, broad jump, 20- and 60-yard shuttles, three-cone drill, and the Wonderlic Personnel Test. Performance criteria include 10 variables: draft order; 3 years each of salary received and games played; and position-specific data. Using correlation analysis, we find no consistent statistical relationship between combine tests and professional football performance, with the notable exception of sprint tests for running backs. We put forth possible explanations for the general lack of statistical relations detected, and, consequently, we question the overall usefulness of the combine. We also offer suggestions for improving the prediction of success in the NFL, primarily the use of more rigorous psychological tests and the examination of collegiate performance as a job sample test. Finally, from a practical standpoint, the results of the study should encourage NFL team personnel to reevaluate the usefulness of the combine's physical tests and exercises as predictors of player performance. This study should encourage team personnel to consider the weighting and importance of various combine measures and the potential benefits of overhauling the combine process, with the goal of creating a more valid system for predicting player success.

360-feedback in health care management: a field study.

In recent years, organizations representing all types of industries, including health care, have adopted the 360-feedback approach with the goal of strengthening leader performance. But while 360-feedback enjoys a high level of face validity, current research shows that it is not problem-free and often fails to achieve its goals without proper development and implementation. This research, conducted in a large public hospital, surveyed the top management team of 49 executives who participated in a 360-feedback project beginning in February 2001. The survey, designed to solicit opinions about the effectiveness of the 360-feedback project, resulted in several recommendations to improve the process: One, both mentors and participants (raters and those rated) should be formally trained to improve the feedback process. Two, participants--both raters and those rated--should be significantly involved in 360-feedback planning and development efforts. Three, the 360-feedback process should be linked to hospital objectives. Four, the 360-feedback process should focus not only on interpersonal issues but departmental and organizational goals as well. First and foremost, our findings show that regardless of how popular a management development program may be, no technique for improving management and organizational effectiveness, including 360-feedback, will work unless properly designed and implemented.