Multimodel Evidence for an Atmospheric Circulation Response to Arctic Sea Ice Loss in the CMIP5 Future Projections.

Previous single-model experiments have found that Arctic sea ice loss can influence the atmospheric circulation. To evaluate this process in a multimodel ensemble, a novel methodology is here presented and applied to infer the influence of Arctic sea ice loss in the CMIP5 future projections. Sea ice influence is estimated by comparing the circulation response in the RCP8.5 scenario against the circulation response to sea surface warming and CO2 increase inferred from the AMIPFuture and AMIP4xCO2 experiments, where sea ice is unperturbed. Multimodel evidence of the impact of sea ice loss on midlatitude atmospheric circulation is identified in late winter (January-March), when the sea ice-related surface heat flux perturbation is largest. Sea ice loss acts to suppress the projected poleward shift of the North Atlantic jet, to increase surface pressure in northern Siberia, and to lower it in North America. These features are consistent with previous single-model studies, and the present results indicate that they are robust to model formulation.

Husk to caryopsis adhesion in barley is influenced by pre- and post-anthesis temperatures through changes in a cuticular cementing layer on the caryopsis.

BACKGROUND: At ripeness, the outer husk of "covered" barley grains firmly adheres to the underlying caryopsis. A cuticular cementing layer on the caryopsis is required for husk adhesion, however the quality of adhesion varies significantly among cultivars which produce the cementing layer, resulting in the economically important malting defect, grain skinning. The composition of the cementing layer, and grain organ development have been hypothesised to influence the quality of husk adhesion. Plants of Hordeum vulgare 'Concerto' were grown at different temperatures pre- and post-anthesis to effect changes in the development of the husk, caryopsis and cuticular cementing layer, to determine how these variables influence the quality of husk-to-caryopsis adhesion. RESULTS: Warm conditions pre-anthesis decreased the quality of husk adhesion, and consequently increased the incidence of grain skinning. Cool post-anthesis conditions further decreased the quality of husk adhesion. The composition of the cementing layer, rather than its structure, differed with respect to husk adhesion quality. This cementing layer was produced at the late milk stage, occurring between nine and 29 days post-anthesis, conditional on the temperature-dependent growth rate. The compounds octadecanol, tritriacontane, campesterol and ß-sitosterol were most abundant in caryopses with high-quality husk adhesion. The differences in adhesion quality were not due to incompatible husk and caryopsis dimensions affecting organ contact. CONCLUSIONS: This study shows that husk-to-caryopsis adhesion is dependent on cementing layer composition, and implies that this composition is regulated by temperature before, and during grain development. Understanding this regulation will be key to improving husk-to-caryopsis adhesion.

Environmental assessment of three egg production systems--Part I: Monitoring system and indoor air quality.

To comprehensively assess conventional vs. some alternative laying-hen housing systems under U.S. production conditions, a multi-institute and multi-disciplinary project, known as the Coalition for Sustainable Egg Supply (CSES) study, was carried out at a commercial egg production farm in the Midwestern United States over two single-cycle production flocks. The housing systems studied include a conventional cage house (200,000 hen capacity), an aviary house (50,000 hen capacity), and an enriched colony house (50,000 hen capacity). As an integral part of the CSES project, continual environmental monitoring over a 27-month period described in this paper quantifies indoor gaseous and particulate matter concentrations, thermal environment, and building ventilation rate of each house. Results showed that similar indoor thermal environments in all three houses were maintained through ventilation management and environmental control. Gaseous and particulate matter concentrations of the enriched colony house were comparable with those of the conventional cage house. In comparison, the aviary house had poorer indoor air quality, especially in wintertime, resulting from the presence of floor litter (higher ammonia levels) and hens' activities (higher particulate matter levels) in it. Specifically, daily mean indoor ammonia concentrations had the 95% confidence interval values of 3.8 to 4.2 (overall mean of 4.0) ppm for the conventional cage house; 6.2 to 7.2 (overall mean of 6.7) ppm for the aviary house; and 2.7 to 3.0 (overall mean of 2.8) ppm for the enriched colony house. The 95% confidence interval (overall mean) values of daily mean indoor carbon dioxide concentrations were 1997 to 2170 (2083) ppm for the conventional cage house, 2367 to 2582 (2475) ppm for the aviary house, and 2124 to 2309 (2216) ppm for the enriched colony house. Daily mean indoor methane concentrations were similar for all three houses, with 95% confidence interval values of 11.1 to 11.9 (overall mean of 11.5) ppm. The 95% confidence interval values (overall mean) of daily mean PM10 and PM2.5 concentrations, in mg/m3, were, respectively, 0.57 to 0.61 (0.59) and 0.033 to 0.037 (0.035) for the conventional cage house, 3.61 to 4.29 (3.95) and 0.374 to 0.446 (0.410) for the aviary house, and 0.42 to 0.46 (0.44) and 0.054 to 0.059 (0.056) for the enriched colony house. Investigation of mitigation practices to improve indoor air quality of the litter-floor aviary housing system is warranted.

Comparative evaluation of three egg production systems: Housing characteristics and management practices.

This paper is an integral part of the special publication series that arose from the multidisciplinary and multi-institutional project of the Coalition for Sustainable Egg Supply (CSES). The CSES project involves 3 housing systems for egg production at the same research farm site in the Midwest, USA, namely, a conventional cage (CC) house, an aviary (AV) house, and an enriched colony (EC) house. The CC house (141.4 m L×26.6 m W×6.1 m H) had a nominal capacity of 200,000 hens (6 hens in a cage at a stocking density of 516 cm2/hen), and the cages were arranged in 10 rows, 8 tiers per cage row, with a perforated aisle walkway at 4-tier height. The AV house (154.2 m L×21.3 m W×3.0 m H) and the EC house (154.2 m L×13.7 m W×4.0 m H) each had a nominal capacity of 50,000 hens. The AV house had 6 rows of aviary colonies, and the EC house had 5 rows of 4-tier enriched colonies containing perches, nestbox, and scratch pads (60 hens per colony at a stocking density of 752 cm2/hen). The overarching goal of the CSES project, as stated in the opening article of this series, was to comprehensively evaluate the 3 egg production systems from the standpoints of animal behavior and well-being, environmental impact, egg safety and quality, food affordability, and worker health. So that all the area-specific papers would not have to repeat a detailed description of the production systems and the management practices, this paper is written to provide such a description and to be used as a common reference for the companion papers.

Environmental assessment of three egg production systems--Part II. Ammonia, greenhouse gas, and particulate matter emissions.

As an integral part of the Coalition for Sustainable Egg Supply (CSES) Project, this study simultaneously monitored air emissions of 3 commercially operated egg production systems at the house level and associated manure storage over 2 single-cycle flocks (18 to 78 wk of age). The 3 housing systems were 1) a conventional cage house (CC) with a 200,000-hen capacity (6 hens in a cage at a stocking density of 516 cm2/hen), 2) an enriched colony house (EC) with a 50,000-hen capacity (60 hens per colony at a stocking density of 752 cm2/hen), and 3) an aviary house (AV) with a 50,000-hen capacity (at a stocking density of 1253 to 1257 cm2/hen). The 3 hen houses were located on the same farm and were populated with Lohmann white hens of the same age. Indoor environment and house-level gaseous (ammonia [NH3] and greenhouse gasses [GHG], including carbon dioxide [CO2], methane [CH4], and nitrous oxide [N2O]) and particulate matter (PM10, PM2.5) emissions were monitored continually. Gaseous emissions from the respective manure storage of each housing system were also monitored. Emission rates (ERs) are expressed as emission quantities per hen, per animal unit (AU, 500 kg live BW), and per kilogram of egg output. House-level NH3 ER (g/hen/d) of EC (0.054) was significantly lower than that of CC (0.082) or AV (0.112) (P<0.05). The house-level CO2 ER (g/hen/d) was lower for CC (68.3) than for EC and AV (74.4 and 74.0, respectively), and the CH4 ER (g/hen/d) was similar for all 3 houses (0.07 to 0.08). The house-level PM ER (mg/hen/d), essentially representing the farm-level PM ER, was significantly higher for AV (PM10 100.3 and PM2.5 8.8) than for CC (PM10 15.7 and PM2.5 0.9) or EC (PM10 15.6 and PM2.5 1.7) (P<0.05). The farm-level (house plus manure storage) NH3 ER (g/hen/d) was significantly lower for EC (0.16) than for CC (0.29) or AV (0.30) (P<0.05). As expected, the magnitudes of GHG emissions were rather small for all 3 production systems. Data from this study enable comparative assessment of conventional vs. alternative hen housing systems regarding air emissions and enhance the U.S. national air emissions inventory for farm animal operations.

Impact of commercial housing systems and nutrient and energy intake on laying hen performance and egg quality parameters.

The US egg industry is exploring alternative housing systems for laying hens. However, limited published research related to cage-free aviary systems and enriched colony cages exists related to production, egg quality, and hen nutrition. The laying hen's nutritional requirements and resulting productivity are well established with the conventional cage system, but diminutive research is available in regards to alternative housing systems. The restrictions exist with limited availability of alternative housing systems in research settings and the considerable expense for increased bird numbers in a replicate due to alternative housing system design. Therefore, the objective of the current study was to evaluate the impact of nutrient and energy intake on production and egg quality parameters from laying hens housed at a commercial facility. Lohmann LSL laying hens were housed in three systems: enriched colony cage, cage-free aviary, and conventional cage at a single commercial facility. Daily production records were collected along with dietary changes during 15 production periods (28-d each). Eggs were analyzed for shell strength, shell thickness, Haugh unit, vitelline membrane properties, and egg solids each period. An analysis of covariance (ANCOVA) coupled with a principal components analysis (PCA) approach was utilized to assess the impact of nutritional changes on production parameters and monitored egg quality factors. The traits of hen-day production and mortality had a response only in the PCA 2 direction. This finds that as house temperature and Met intake increases, there is an inflection point at which hen-day egg production is negatively effected. Dietary changes more directly influenced shell parameters, vitelline membrane parameters, and egg total solids as opposed to laying hen housing system. Therefore, further research needs to be conducted in controlled research settings on laying hen nutrient and energy intake in the alternative housing systems and resulting impact on egg quality measures.

Use of zinc deposited in deciduous teeth as a retrospective measurement of dietary zinc exposure during early development.

Purpose: We proposed that zinc (Zn) deposition in deciduous teeth would be a timed record of exposure to this essential micronutrient over very early life. We tested this hypothesis by gathering information on the maternal and child's diet during pregnancy and early infancy and measuring mineral deposition in the dentine at points during deciduous tooth development. Methods: We developed a short food frequency questionnaire (S-FFQ) to record consumption of food containing Zn during pregnancy and over the first year of life of the child in an Indonesian population. Zn, Sr and Ca were measured by laser ablation ICP-MS in a series of points across the developmental timeline in deciduous teeth extracted from 18 children undergoing the process as part of dental treatment whose mothers completed the SFFQ. Mothers and children were classified into either high Zn or low Zn groups according to calculated daily Zn intake. Results: The Zn/Sr ratio in dentine deposited over late pregnancy and 0-3 months post-partum was higher (p < 0.001, 2-way ANOVA; p < 0.05 by Holm-Sidak post hoc test) in the teeth of children of mothers classified as high Zn consumers (n = 10) than in children of mothers classified as low Zn consumers (n = 8). Conclusion: The S-FFQ was validated internally as adequately accurate to measure zinc intake retrospectively during pregnancy and post-partum (∼7 years prior) by virtue of the correlation with measurements of zinc in deciduous teeth. The ratio of Zn/Sr in deciduous teeth appears to be a biomarker of exposure to zinc nutrition during early development and offers promise for use as a record of prior exposure along a timeline for research studies and, potentially, to identify individuals at heightened risk of detrimental impacts of poor early life zinc nutrition on health in later life and to implement preventative interventions.

Improved limits on spin-dependent WIMP-proton interactions from a two liter CF3I bubble chamber.

Data from the operation of a bubble chamber filled with 3.5 kg of CF3I in a shallow underground site are reported. An analysis of ultrasound signals accompanying bubble nucleations confirms that alpha decays generate a significantly louder acoustic emission than single nuclear recoils, leading to an efficient background discrimination. Three dark matter candidate events were observed during an effective exposure of 28.1 kg day, consistent with a neutron background. This observation provides strong direct detection constraints on weakly interacting massive particle (WIMP)-proton spin-dependent scattering for WIMP masses >20 GeV/c2.

Simultaneous Multislice for Accelerating Diffusion MRI in Clinical Neuroradiology Protocols.

BACKGROUND AND PURPOSE: Diffusion MR imaging sequences essential for clinical neuroradiology imaging protocols may be accelerated with simultaneous multislice acquisitions. We tested whether simultaneous multislice-accelerated diffusion data were clinically equivalent to standard acquisitions. MATERIALS AND METHODS: In this retrospective study, clinical diffusion sequences obtained before and after implementation of 2-slice simultaneous multislice acceleration and an altered diffusion gradient sampling scheme using the same 3T MRI scanner and 20-channel coil (n = 25 per group) were independently and blindly evaluated by 2 neuroradiologists for perceived quality, artifacts, and overall diagnostic utility. Diffusion tractography was performed in 13 patients both with and without 2-slice simultaneous multislice acceleration (b = 0, 1000, 2000 s/mm2; 60 directions). The corticospinal tract and arcuate fasciculus ipsilateral to the lesion were generated using the same ROIs and then blindly assessed by a neurosurgeon for anatomic fidelity, perceived quality, and impact on surgical management. Tract volumes were compared for spatial overlap. RESULTS: Two-slice simultaneous multislice diffusion reduced acquisition times from 141 to 45 seconds for routine diffusion and from 7.5 to 5.9 minutes for diffusion tractography using 3T MR imaging. The simultaneous multislice-accelerated diffusion sequence was rated equivalent for diagnostic utility despite reductions to perceived image quality. Simultaneous multislice-accelerated diffusion tractography was rated clinically equivalent. Dice similarity coefficients between routine and simultaneous multislice-generated corticospinal tract and arcuate fasciculus tract volumes were 0.78 (SD, 0.03) and 0.71 (SD, 0.05), respectively. CONCLUSIONS: Two-slice simultaneous multislice diffusion appeared clinically equivalent for standard acquisitions and diffusion tractography. Simultaneous multislice makes it feasible to acquire higher angular and q-space-resolution diffusion acquisitions required for translating advanced diffusion models into clinical practice.

20% of US electricity from wind will have limited impacts on system efficiency and regional climate.

Impacts from current and future wind turbine (WT) deployments necessary to achieve 20% electricity from wind are analyzed using high resolution numerical simulations over the eastern USA. Theoretical scenarios for future deployments are based on repowering (i.e. replacing with higher capacity WTs) thus avoiding competition for land. Simulations for the contemporary climate and current WT deployments exhibit good agreement with observed electricity generation efficiency (gross capacity factors (CF) from simulations = 45-48%, while net CF for WT installed in 2016 = 42.5%). Under the scenario of quadrupled installed capacity there is a small decrease in system-wide efficiency as indicated by annual mean CF. This difference is approximately equal to that from the two simulation years and may reflect saturation of the wind resource in some areas. WT modify the local near-surface climate in the grid cells where they are deployed. The simulated impact on near-surface climate properties at both the regional and local scales does not increase with increasing WT installed capacity. Climate impacts from WT are modest compared to regional changes induced by historical changes in land cover and to the global temperature perturbation induced by use of coal to generate an equivalent amount of electricity.

MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei.

The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.

Direct In Vivo MRI Discrimination of Brain Stem Nuclei and Pathways.

BACKGROUND AND PURPOSE: The brain stem is a complex configuration of small nuclei and pathways for motor, sensory, and autonomic control that are essential for life, yet internal brain stem anatomy is difficult to characterize in living subjects. We hypothesized that the 3D fast gray matter acquisition T1 inversion recovery sequence, which uses a short inversion time to suppress signal from white matter, could improve contrast resolution of brain stem pathways and nuclei with 3T MR imaging. MATERIALS AND METHODS: After preliminary optimization for contrast resolution, the fast gray matter acquisition T1 inversion recovery sequence was performed in 10 healthy subjects (5 women; mean age, 28.8 ± 4.8 years) with the following parameters: TR/TE/TI = 3000/2.55/410 ms, flip angle = 4°, isotropic resolution = 0.8 mm, with 4 averages (acquired separately and averaged outside k-space to reduce motion; total scan time = 58 minutes). One subject returned for an additional 5-average study that was combined with a previous session to create a highest quality atlas for anatomic assignments. A 1-mm isotropic resolution, 12-minute version, proved successful in a patient with a prior infarct. RESULTS: The fast gray matter acquisition T1 inversion recovery sequence generated excellent contrast resolution of small brain stem pathways in all 3 planes for all 10 subjects. Several nuclei could be resolved directly by image contrast alone or indirectly located due to bordering visualized structures (eg, locus coeruleus and pedunculopontine nucleus). CONCLUSIONS: The fast gray matter acquisition T1 inversion recovery sequence has the potential to provide imaging correlates to clinical conditions that affect the brain stem, improve neurosurgical navigation, validate diffusion tractography of the brain stem, and generate a 3D atlas for automatic parcellation of specific brain stem structures.

3T MRI Whole-Brain Microscopy Discrimination of Subcortical Anatomy, Part 1: Brain Stem.

BACKGROUND AND PURPOSE: The brain stem is compactly organized with life-sustaining sensorimotor and autonomic structures that can be affected by numerous pathologies but can be difficult to resolve on conventional MR imaging. MATERIALS AND METHODS: We applied an optimized TSE T2 sequence to washed postmortem brain samples to reveal exquisite and reproducible brain stem anatomic MR imaging contrast comparable with histologic atlases. This resource-efficient approach can be performed across multiple whole-brain samples with relatively short acquisition times (2 hours per imaging plane) using clinical 3T MR imaging systems. RESULTS: We identified most brain stem structures at 7 canonical axial levels. Multiplanar or oblique planes illustrate the 3D course and spatial relationships of major brain stem white matter pathways. Measurements of the relative position, course, and cross-sectional area of these pathways across multiple samples allow estimation of pathway location in other samples or clinical subjects. Possible structure-function asymmetries in these pathways will require further study-that is, the cross-sectional area of the left corticospinal tract in the midpons appeared 20% larger (n = 13 brains, P < .10). CONCLUSIONS: Compared with traditional atlases, multiplanar MR imaging contrast has advantages for learning and retaining brain stem anatomy for clinicians and trainees. Direct TSE MR imaging sequence discrimination of brain stem anatomy can help validate other MR imaging contrasts, such as diffusion tractography, or serve as a structural template for extracting quantitative MR imaging data in future postmortem investigations.

Risk Factors for Perceptual-versus-Interpretative Errors in Diagnostic Neuroradiology.

BACKGROUND AND PURPOSE: Diagnostic errors in radiology are classified as perception or interpretation errors. This study determined whether specific conditions differed when perception or interpretation errors occurred during neuroradiology image interpretation. MATERIALS AND METHODS: In a sample of 254 clinical error cases in diagnostic neuroradiology, we classified errors as perception or interpretation errors, then characterized imaging technique, interpreting radiologist's experience, anatomic location of the abnormality, disease etiology, time of day, and day of the week. Interpretation and perception errors were compared with hours worked per shift, cases read per shift, average cases read per shift hour, and the order of case during the shift when the error occurred. RESULTS: Perception and interpretation errors were 74.8% (n = 190) and 25.2% (n = 64) of errors, respectively. Logistic regression analyses showed that the odds of an interpretation error were 2 times greater (OR, 2.09; 95% CI, 1.05-4.15; P = .04) for neuroradiology attending physicians with ≤5 years of experience. Interpretation errors were more likely with MR imaging compared with CT (OR, 2.10; 95% CI, 1.09-4.01; P = .03). Infectious/inflammatory/autoimmune diseases were more frequently associated with interpretation errors (P = .04). Perception errors were associated with faster reading rates (6.01 versus 5.03 cases read per hour; P = .004) and occurred later during the shift (24th-versus-18th case; P = .04). CONCLUSIONS: Among diagnostic neuroradiology error cases, interpretation-versus-perception errors are affected by the neuroradiologist's experience, technique, and the volume and rate of cases read. Recognition of these risk factors may help guide programs for error reduction in clinical neuroradiology services.

3T MRI Whole-Brain Microscopy Discrimination of Subcortical Anatomy, Part 2: Basal Forebrain.

BACKGROUND AND PURPOSE: The basal forebrain contains multiple structures of great interest to emerging functional neurosurgery applications, yet many neuroradiologists are unfamiliar with this neuroanatomy because it is not resolved with current clinical MR imaging. MATERIALS AND METHODS: We applied an optimized TSE T2 sequence to washed whole postmortem brain samples (n = 13) to demonstrate and characterize the detailed anatomy of the basal forebrain using a clinical 3T MR imaging scanner. We measured the size of selected internal myelinated pathways and measured subthalamic nucleus size, oblique orientation, and position relative to the intercommissural point. RESULTS: We identified most basal ganglia and diencephalon structures using serial axial, coronal, and sagittal planes relative to the intercommissural plane. Specific oblique image orientations demonstrated the positions and anatomic relationships for selected structures of interest to functional neurosurgery. We observed only 0.2- to 0.3-mm right-left differences in the anteroposterior and superoinferior length of the subthalamic nucleus (P = .084 and .047, respectively). Individual variability for the subthalamic nucleus was greatest for angulation within the sagittal plane (range, 15°-37°), transverse dimension (range, 2-6.7 mm), and most inferior border (range, 4-7 mm below the intercommissural plane). CONCLUSIONS: Direct identification of basal forebrain structures in multiple planes using the TSE T2 sequence makes this challenging neuroanatomy more accessible to practicing neuroradiologists. This protocol can be used to better define individual variations relevant to functional neurosurgical targeting and validate/complement advanced MR imaging methods being developed for direct visualization of these structures in living patients.

Using biochemical and isotope geochemistry to understand the environmental and public health implications of lead pollution in the lower Guadiana River, Iberia: a freshwater bivalve study.

Lead is a natural component of aquatic ecosystems with no known biological role and is highly toxic. Its toxicity stems from its ability to mimic biologically important metals and to produce membrane damage through lipid peroxidation (LPO). Most lead poisoning symptoms are thought to occur by interfering with an essential enzyme, delta-aminolevulinic acid dehydratase (ALAD), the activity of which is markedly inhibited by lead. The purpose of this work was to study the levels and effects of lead pollution (responses of ALAD and oxidative stress biomarker LPO) in the freshwater bivalve Corbicula fluminea along the lower Guadiana River (Portugal and Spain); a major river system impacted by historic mining pollution and more recent anthropogenic inputs. The results show that the enzymatic activity of ALAD is negatively correlated with the total Pb concentration of the whole tissue suggesting that ALAD has considerable potential as a biomarker of lead exposure in C. fluminea. To identify the sources of lead to which bivalves have been exposed, high precision (206)Pb/(204)Pb, (207)Pb/(204)Pb, (208)Pb/(204)/Pb ratios for C. fluminea confirm that historical mining activities in the Iberian Pyrite Belt are the dominant source of lead pollution in the lower Guadiana River. The isotope patterns however exhibit marked seasonal and geographic variation in response to rainfall and river water management. Locally, other anthropogenic sources of lead have been detected in C. fluminea close to population centres, thus adding to its versatility as a freshwater bio-indicator. Overall, the study highlights the value of natural ecosystems as monitors of water quality and their importance for public health assessment and surveillance.

The pea3 subfamily ets genes are required for HER2/Neu-mediated mammary oncogenesis.

BACKGROUND: The PEA3 Ets transcription factor is overexpressed in the vast majority of human breast tumors and in nearly all of those of the HER2/Neu-positive subclass. PEA3 is also overexpressed in various transgenic mouse models of this disease. Whether PEA3 plays an essential role in HER2/Neu-mediated oncogenesis has heretofore not been addressed. RESULTS: Here, we report that each of the three highly related ets genes of the pea3 subfamily (pea3, er81, and erm) were coordinately overexpressed in mammary tumors of MMTV-neu transgenic mice. Other ets genes normally expressed in the mammary gland were not upregulated in these tumors. Expression of a dominant-negative pea3 transgene under the control of the MMTV promoter in mammary epithelial cells of MMTV-neu transgenic mice dramatically delayed the onset of mammary tumors and reduced the number and size of such tumors in individual mice. Those tumors that arose in bitransgenic mice expressed the MMTV-neu transgene, but not the MMTV-dominant-negative pea3 transgene. CONCLUSIONS: These findings imply that one or more of the PEA3 subfamily Ets proteins or other Ets proteins with related DNA binding specificity play an essential role in Neu-mediated mammary oncogenesis. Hence, agents that inhibit the expression or activity of the PEA3 subfamily proteins may prove efficacious in the treatment of breast cancer.

Diffusion tensor microscopy indicates the cytoarchitectural basis for diffusion anisotropy in the human hippocampus.

BACKGROUND AND PURPOSE: Observing changes to water diffusivity and fractional anisotropy (FA) for particular hippocampal regions may improve the sensitivity and specificity of diffusion tensor MR imaging for hippocampal pathologies like Alzheimer disease and mesial temporal sclerosis. As a first step toward this goal, this study characterized the cytoarchitectural features underlying diffusion anisotropy in human hippocampus autopsy specimens at 60-microm in-plane resolution. MATERIALS AND METHODS: Eight-millimeter coronal segments of the hippocampal body were dissected from 5 autopsy specimens (mean = 55.6 +/- 6.2 years of age) with short postmortem intervals to fixation (21.2 +/- 5.7 hours) and no histologic evidence of neuropathology. Diffusion tensor microscopy data were collected from hippocampal specimens by using a 14.1T magnet with a protocol that included 21 unique diffusion gradient orientations (diffusion time = 17 ms, b = 1250 s/mm(2)). The resulting images were used to determine the mean diffusivity, FA, and principal fiber orientation for manually segmented hippocampal regions that included the stratum oriens, stratum radiatum, stratum pyramidale (CA1 and CA3), stratum lacunosum-molecular, hilus, molecular layer, granule cell layer, fimbria, and subiculum. RESULTS: Diffusion-weighted images had high signal-to-noise ratios (31.1 +/- 13.0) and delineated hippocampal anatomy well. Water diffusivity ranged from 1.21 +/- 0.22 x 10(-4) mm(2)/s in the fimbria to 3.48 +/- 0.72 x 10(-4) mm(2)/s in granule cells (analysis of variance, P<.001). Color fiber-orientation maps indicated the underlying microstructures responsible for diffusion anisotropy in the hippocampal lamina. CONCLUSION: Diffusion tensor microscopy provided novel microstructural information about the different lamina of the human hippocampus. These ex vivo data obtained at high-magnetic-field strengths can be used to study injury-specific diffusion changes to susceptible hippocampal regions and may lead to more specific MR imaging surrogate markers for Alzheimer disease or epilepsy.

Palliative CT-Guided Cordotomy for Medically Intractable Pain in Patients with Cancer.

Palliative cervical cordotomy can be performed via percutaneous radiofrequency ablation of the lateral C1-2 spinothalamic tract. This rare procedure can be safe, effective, and advantageous in mitigating medically intractable unilateral extremity pain for selected patients with end-stage cancer. This report reviews the indications, techniques, risks, and potential benefits of cordotomy. We describe our recent experience treating 3 patients with CT-guided C1-2 cordotomy and provide the first characterization of spinal cord diffusion MR imaging changes associated with successful cordotomy.

Site-specific prodrug activation by antibody-beta-lactamase conjugates: regression and long-term growth inhibition of human colon carcinoma xenograft models.

Antibody-directed catalysis (ADC) is a two-step method for the delivery of chemotherapeutic agents in which enzyme-antibody conjugate, prelocalized to antigen-bearing tumor cells, catalyzes the site-specific conversion of prodrug to drug. An ADC system consisting of F(ab')-beta-lactamase conjugates and a cephalosporin derivative of the oncolytic agent 4-desacetylvinblastine-3-carboxhydrazide was investigated. The ability of the system to mediate antitumor activity was compared with that of free drug given alone and with covalent drug-antibody conjugates in LS174T and T380 colon carcinoma xenografts in nude mice. Efficacy increased from moderate tumor growth inhibition by using free 4-desacetylvinblastine-3-carboxhydrazide to tumor regression and long-term stabilization with the ADC system. Labile covalent drug-antibody conjugates prepared from the same antibodies were less effective than ADC and required much higher antibody doses. The antigens KS1/4, carcinoembryonic antigen, and tumor-associated glycoprotein-72, TAG-72, present on the model cell lines, were chosen to investigate the effect of differences in subcellular location and expression heterogeneity on the efficacy of ADC delivery. Response was equivalent with the three tumor antigens. Hence, heterogeneous expression and membrane shedding of carcinoembryonic antigen and TAG-72, did not diminish the suitability of these antigens as targets for ADC therapy. In contrast, drug-antibody conjugate efficacy was more sensitive to subcellular location and heterogeneity. Thus, ADC is a highly effective form of immunochemotherapy in preclinical models, with applicability toward a variety of antigen targets.