Mutations in nuclear genes encoding mitochondrial ribosome proteins restore pollen fertility in S male-sterile maize.

The interaction of plant mitochondrial and nuclear genetic systems is exemplified by mitochondria-encoded cytoplasmic male sterility (CMS) under the control of nuclear restorer-of-fertility genes. The S type of CMS in maize is characterized by a pollen collapse phenotype and a unique paradigm for fertility restoration in which numerous nuclear restorer-of-fertility lethal mutations rescue pollen function but condition homozygous-lethal seed phenotypes. Two nonallelic restorer mutations recovered from Mutator transposon-active lines were investigated to determine the mechanisms of pollen fertility restoration and seed lethality. Mu Illumina sequencing of transposon-flanking regions identified insertion alleles of nuclear genes encoding mitochondrial ribosomal proteins RPL6 and RPL14 as candidate restorer-of-fertility lethal mutations. Both candidates were associated with lowered abundance of mitochondria-encoded proteins in developing maize pollen, and the rpl14 mutant candidate was confirmed by independent insertion alleles. While the restored pollen functioned despite reduced accumulation of mitochondrial respiratory proteins, normal-cytoplasm plants heterozygous for the mutant alleles showed a significant pollen transmission bias in favor of the nonmutant Rpl6 and Rpl14 alleles. CMS-S fertility restoration affords a unique forward genetic approach to investigate the mitochondrial requirements for, and contributions to, pollen and seed development.

Stability of extemporaneously compounded 5-fluorouracil utilizing high performance liquid chromatography.

The goal of the current study is to determine stability of compounded 5-fluorouracil (5-FU) in Intravia™ bags and CADD™ cassettes stored up to 15 days under refrigeration (2-8°C) and room temperature (25°C with 60% relative humidity), with four different concentrations (20 mg/mL, 30 mg/mL, 40 mg/mL, and 50 mg/mL) and two diluents (0.9% sodium chloride and 5% dextrose). A stability-indicating high-performance liquid chromatography (HPLC) method was developed to analyze the 5-FU concentrations. The stability of compounded 5-FU infusions was investigated using this method. Two samples from each storage condition were assessed for stability on days 0, 4, 7, 10, and 15 as per United States Pharmacopeia (USP) guidelines. The assay of 5-FU was done utilizing a calibrated stability-indicating HPLC method. The stability-indicating HPLC assay showed 5-FU completely degraded within 1 hour in basic conditions. No cloudiness or color change was observed during the stability study. Precipitation was observed in the CADD™ cassettes at day 15 in both storage conditions and at day 10 in a single room-temperature CADD™ cassette for 40 mg/mL in 5% dextrose (D5W). HPLC assay revealed the infusions in CADD™ cassettes retained greater than 90% of the initial concentrations of 5-FU for 15 days stored at room temperature (25°C and 60% relative humidity) and for 10 days at refrigeration (2-8°C). Intravia™ bags retained stability through 15 days for all the compounded 5-FU concentrations and both the storage conditions. 5-FU infusions in both CADD™ cassettes and Intravia™ bags were stable for extendable periods in multiple concentrations compared to recommended guidelines for hospital use.

SPECT/CT image-based dosimetry for Yttrium-90 radionuclide therapy: Application to treatment response.

This work demonstrates the efficacy of voxel-based 90 Y microsphere dosimetry utilizing post-therapy SPECT/CT imaging and applies it to the prediction of treatment response for the management of patients with hepatocellular carcinoma (HCC). A 90 Y microsphere dosimetry navigator (RapidSphere) within a commercial platform (Velocity, Varian Medical Systems) was demonstrated for three microsphere cases that were imaged using optimized bremsstrahlung SPECT/CT. For each case, the 90 Y SPECT/CT was registered to follow-up diagnostic MR/CT using deformable image registration. The voxel-based dose distribution was computed using the local deposition method with known injected activity. The system allowed the visualization of the isodose distributions on any of the registered image datasets and the calculation of dose-volume histograms (DVHs). The dosimetric analysis illustrated high local doses that are characteristic of blood-flow directed brachytherapy. In the first case, the HCC mass demonstrated a complete response to treatment indicated by a necrotic region in follow-up MR imaging. This result was dosimetrically predicted since the gross tumor volume (GTV) was well covered by the prescription isodose volume (V150 Gy = 85%). The second case illustrated a partial response to treatment which was characterized by incomplete necrosis of an HCC mass and a remaining area of solid enhancement in follow-up MR imaging. This result was predicted by dosimetric analysis because the GTV demonstrated incomplete coverage by the prescription isodose volume (V470 Gy = 18%). The third case demonstrated extrahepatic activity. The dosimetry indicated that the prescription (125 Gy) isodose region extended outside of the liver into the duodenum (178 Gy maximum dose). This was predictive of toxicity as the patient later developed a duodenal ulcer. The ability to predict outcomes and complications using deformable image registration, calculated isodose distributions, and DVHs, points to the clinical utility of patient-specific dose calculations for 90 Y radioembolization treatment planning.

RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNEA AND THE PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY.

PURPOSE: To evaluate the relationship between obstructive sleep apnea (OSA) and the presence and severity of diabetic retinopathy (DR). METHODS: Three hundred seventeen patients with International Classification of Diseases diagnoses of both DR and OSA were evaluated retrospectively. Diabetic retinopathy severity and diabetic macular edema status were determined by diagnostic coding and medical records. Obstructive sleep apnea severity and additional sleep measures were obtained from overnight polysomnography. Analysis was performed using multivariable logistic regression. RESULTS: After adjustment, an association was seen between DR and severe OSA (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.14-4.18, P = 0.019). Proliferative DR was associated with severe OSA versus no DR (OR: 2.40, 95% CI: 1.12-5.14, P = 0.024) and mild nonproliferative DR (OR: 2.87, 95% CI: 1.26-6.55, P = 0.012). Comparing all nonproliferative DR with proliferative DR, proliferative DR and severe OSA were associated (OR: 2.20, 95% CI: 1.03-4.70, P = 0.043), as well as diabetic macular edema and severe OSA (OR: 2.89, 95% CI: 1.58-5.27, P = 0.001). No association was seen between DR/diabetic macular edema and secondary sleep measures. CONCLUSION: The findings suggest an increased risk of DR, proliferative DR, and diabetic macular edema in patients with severe OSA. Ophthalmologists following these patients should be aware of this association to better manage ocular sequelae of diabetes.

Association Between Eyelid Laxity and Obstructive Sleep Apnea.

Importance: While much has been reported on the relationship between floppy eyelid syndrome and obstructive sleep apnea (OSA), the diagnostic criteria of floppy eyelid syndrome are often subjective and vague. Objective: To evaluate the association between OSA and quantitative markers of eyelid laxity or secondary ocular surface disease in a sleep clinic population. Design, Setting, and Participants: This investigation was a cross-sectional observational study at the Center for Sleep Medicine at Icahn School of Medicine at Mount Sinai. Participants were individuals referred for overnight polysomnography from March 1 to August 30, 2015. Main Outcomes and Measures: Eyelid laxity and ocular surface disease were assessed on bedside ophthalmologic examination. The presence and severity of OSA were determined from polysomnography results. Initial correlation between OSA and ocular surface and eyelid markers was calculated through bivariate linear regression analysis, and the association between ocular symptoms was obtained through bivariate ordered logistic regression. Analysis was repeated adjusting for known associations between OSA and sex, age, body mass index, and medical comorbidities through multivariable analysis. Results: In total, 201 individuals (402 eyes) were enrolled in the study. Their mean (SD) age was 53.2 (13.5) years, 43.3% (n = 87) were female, 56.7% (n = 114) were of white race/ethnicity, 26.9% (n = 54) were black/African American, 4.0% (n = 8) were Asian, 8.0% (n = 16) were multiracial or other, and 4.5% (n = 9) were of unknown race/ethnicity, with 21.9% (n = 44) of all individuals self-identifying as Hispanic and 75.1% (n = 151) self-identifying as non-Hispanic. After adjustment, no association was observed between OSA severity and an eyelid laxity score (regression coefficient, 0.85; 95% CI, -0.33 to 0.62; P = .40) or an ocular surface score (regression coefficient, 1.09; 95% CI, -0.32 to 0.29; P = .93). Through subset analysis, male sex was associated with a higher ocular surface score, while older age and diabetes were associated with a higher eyelid laxity score. Only one patient (0.5%) exhibited findings of floppy eyelid syndrome. Conclusions and Relevance: Among individuals referred for overnight polysomnography, quantitative markers of eyelid laxity were not associated with the presence or severity of OSA. Subset analysis suggests that prior studies may have been limited by confounding variables or the technique of identifying eyelid laxity.

Modelling moose-forest interactions under different predation scenarios at Isle Royale National Park, USA.

Loss of top predators may contribute to high ungulate population densities and chronic over-browsing of forest ecosystems. However, spatial and temporal variability in the strength of interactions between predators and ungulates occurs over scales that are much shorter than the scales over which forest communities change, making it difficult to characterize trophic cascades in forest ecosystems. We applied the LANDIS-II forest succession model and a recently developed ungulate browsing extension to model how the moose population could interact with the forest ecosystem of Isle Royale National Park, USA, under three different wolf predation scenarios. We contrasted a 100-yr future without wolves (no predation) with two predation scenarios (weak, long-term average predation rates and strong, higher than average rates). Increasing predation rates led to lower peak moose population densities, lower biomass removal rates, and higher estimates of forage availability and landscape carrying capacity, especially during the first 40 yr of simulations. Thereafter, moose population density was similar for all predation scenarios, but available forage biomass and the carrying capacity of the landscape continued to diverge among predation scenarios. Changes in total aboveground live biomass and species composition were most pronounced in the no predation and weak predation scenarios. Consistent with smaller-scale studies, high browsing rates led to reductions in the biomass of heavily browsed Populus tremuloides, Betula papyrifera, and Abies balsamea, and increases in the biomass of unbrowsed Picea glauca and Picea mariana, especially after the simulation year 2050, when existing boreal hardwood stands at Isle Royale are projected to senesce. As a consequence, lower predation rates corresponded with a landscape that progressively shifted toward dominance by Picea glauca and Picea mariana, and lacking available forage biomass. Consistencies with previously documented small-scale successional shifts, and population estimates and trends that approximate those from this and other boreal forests that support moose provide some confidence that these dynamics represent a trophic cascade and therefore provide an important baseline against which to evaluate long-term and large-scale effects of alternative predator management strategies on ungulate populations and forest succession.

A generalizable energetics-based model of avian migration to facilitate continental-scale waterbird conservation.

Conserving migratory birds is made especially difficult because of movement among spatially disparate locations across the annual cycle. In light of challenges presented by the scale and ecology of migratory birds, successful conservation requires integrating objectives, management, and monitoring across scales, from local management units to ecoregional and flyway administrative boundaries. We present an integrated approach using a spatially explicit energetic-based mechanistic bird migration model useful to conservation decision-making across disparate scales and locations. This model moves a Mallard-like bird (Anas platyrhynchos), through spring and fall migration as a function of caloric gains and losses across a continental-scale energy landscape. We predicted with this model that fall migration, where birds moved from breeding to wintering habitat, took a mean of 27.5 d of flight with a mean seasonal survivorship of 90.5% (95% Cl = 89.2%, 91.9%), whereas spring migration took a mean of 23.5 d of flight with mean seasonal survivorship of 93.6% (95% CI = 92.5%, 94.7%). Sensitivity analyses suggested that survival during migration was sensitive to flight speed, flight cost, the amount of energy the animal could carry, and the spatial pattern of energy availability, but generally insensitive to total energy availability per se. Nevertheless, continental patterns in the bird-use days occurred principally in relation to wetland cover and agricultural habitat in the fall. Bird-use days were highest in both spring and fall in the Mississippi Alluvial Valley and along the coast and near-shore environments of South Carolina. Spatial sensitivity analyses suggested that locations nearer to migratory endpoints were less important to survivorship; for instance, removing energy from a 1036 km2 stopover site at a time from the Atlantic Flyway suggested coastal areas between New Jersey and North Carolina, including the Chesapeake Bay and the North Carolina piedmont, are essential locations for efficient migration and increasing survivorship during spring migration but not locations in Ontario and Massachusetts. This sort of spatially explicit information may allow decision-makers to prioritize their conservation actions toward locations most influential to migratory success. Thus, this mechanistic model of avian migration provides a decision-analytic medium integrating the potential consequences of local actions to flyway-scale phenomena.

Dysregulated heme oxygenase-ferritin system in pterygium pathogenesis.

PURPOSE: Cyclooxygenase (COX)-, lipoxygenase (LOX)-, and cytochrome P450 monooxygenase (CYP)-derived eicosanoids have been implicated in ocular surface inflammation and neovascularization. These eicosanoids are subjected to regulation by enzymes, such as heme oxygenases (HOs) and ferritin. METHODS: Quantitative polymerase chain reaction and lipidomics based on liquid chromatography-tandem mass spectrometry were performed on pterygia from patients undergoing surgical pterygium excision. Control tissues consisted of donor corneas. In addition, lipidomics based on liquid chromatography-tandem mass spectrometry was performed on tears collected from patients before the surgery. RESULTS: Messenger RNA (mRNA) expression of HO-2, the constitutive HO isoform, was upregulated by 40% in pterygia compared with control tissue, whereas the mRNA level of the inducible form, HO-1, was downregulated by more than 50%. Levels of CYP4B1 mRNA showed an approximate 2-fold increase in pterygia compared with control. Lipidomic analysis of tissues indicated a moderate elevation in Prostaglandin E2 and thromboxane B2 levels in pterygia compared with control. Among the LOX-derived metabolites, the antiinflammatory-hydroxyeicosatetraenoic acid (15-HETE) levels were significantly reduced in pterygia (79.3 ± 48.11 pg/mg protein) compared with control (586.2 ± 213.5 pg/mg protein), whereas the proinflammatory LOX- and CYP4B1-derived 12-HETE levels were 10-fold higher in pterygia (2768 ± 832.3 pg/mg protein) compared with control (231.4 ± 87.35 pg/mg protein). Prostaglandin E2 and HETEs were also present in tears from patients with pterygium but were not detected in tears from healthy volunteers. The mRNA expression levels of both light and heavy chain ferritin were 60% and 30% lower, respectively, in pterygia compared with control. CONCLUSIONS: We believe that a dysfunctional HO-ferritin system leads to increased levels of proinflammatory mediators, thus contributing to the inflammation characteristic of pterygia.

A performance improvement prescribing guideline reduces opioid prescriptions for emergency department dental pain patients.

STUDY OBJECTIVE: In an effort to reduce prescription opioid abuse originating from our institution, we implement and measure the effect of a prescribing guideline on the rate of emergency department (ED) opioid prescriptions written for patients presenting with dental pain, a complaint previously associated with drug-seeking behavior. METHODS: After implementing a departmental guideline on controlled substance prescriptions, we performed a structured before-and-after chart review of dental pain patients aged 16 and older. RESULTS: Before the guideline, the rate of opioid prescription was 59% (302/515). After implementation, the rate was 42% (65/153). The absolute decrease in rates was 17% (95% confidence interval 7% to 25%). Additionally, in comparing the 12-month period before and after implementation, the dental pain visit rate decreased from 26 to 21 per 1,000 ED visits (95% confidence interval of decrease 2 to 9 visits/1,000). CONCLUSION: A performance improvement program involving a departmental prescribing guideline was associated with a reduction in the rate of opioid prescriptions and visits for ED patients presenting with dental pain.

Treatment efficiency of volumetric modulated arc therapy in comparison with intensity-modulated radiotherapy in the treatment of prostate cancer.

PURPOSE: Treatment with intensity-modulated radiation therapy (IMRT) is increasingly standard for prostate cancer. Volume-modulated arc therapy (VMAT) to deliver IMRT potentially enables shorter treatment time. The aim of this study was to test this hypothesis by measuring the average patient in-room time with VMAT versus dynamic multileaf collimator (DMLC) IMRT. METHODS: Custom institutional software (RTMetrix) was used to mine the treatment times from the record-and-verify database. The in-room time (the time between patient entry and exit) was computed for each patient using RTMetrix. Average room time was compared between VMAT patients (n = 44) and IMRT patients (n = 99). Subgroup comparisons (1-arc or 2-arc VMAT, 5-field or 7-field IMRT, and electromagnetic transponder [Calypso] or gold-marker tracking) were performed. For all comparisons, 2-tailed, 2-sample, equal variance Student's t-tests were used. RESULTS: Average room time was significantly shorter for all VMAT versus DMLC IMRT (P = .0014) procedures, along with VMAT versus 7-field DMLC IMRT (P < .001), but not VMAT versus 5-field DMLC IMRT (P = .81). Room time was longer for Calypso versus gold seed patients (P < .001), but VMAT reduced treatment time in Calypso patients (P = .01). This resulted in Calypso VMAT patients' having similar treatment times to non-Calypso DMLC IMRT patients (P = .220). CONCLUSIONS: These data show that VMAT can shorten room times and improve patient throughput over 7-field DMLC IMRT. Additionally, the data demonstrate that treatment with VMAT permits the use of advanced prostate tracking (Calypso), resulting in similar room times as with standard 7-field DMLC IMRT with conventional tracking.

Quantitative analysis of pre- and post-treatment PET-CT scans using deformable image registration methods.

BACKGROUND AND PURPOSE: To investigate the utility of quantitative PET analysis for early prediction of local control following stereotactic body radiation therapy (SBRT). MATERIAL AND METHODS: An initial test cohort of fourteen cases and a validation cohort of twenty-three cases were analyzed. All patients had metastatic or recurrent cancer and underwent PET-CTs pre- and post- SBRT to a variety of sites. Local failure was defined as biopsy proven persistent/recurrent disease or progressive disease on radiologic imaging. Using deformable registration, radiation dose was transferred to the PET-CTs. Using the prescription isodose as the volume of interest (VOI), response was assessed by generating metabolic volume histograms (MVH). MVH curves examine metabolic heterogeneity in the VOI. Exploratory analyses of the test cohort evaluated the viability of multiple iso-SUV and iso-volumetric points selected from the MVH curves to serve as novel markers of response. Standard PET response markers (maximum/mean SUV and qualitative analysis) were also assessed. RESULTS: In the initial cohort, ten of fourteen patients achieved local control at last follow-up, a median of 225 days following post-SBRT PET. Three out of four local failures had an increase in max SUV, while all patients who achieved local control had a reduction in max SUV (p=0.01). Exploratory analyses using multiple iso-SUV and iso-volumetric points did not yield any factors associated with local control (p>0.05). In the validation cohort, lower post- treatment max SUV (p=.03) and reduction in max SUV (p<0.05) were significantly associated with local control. CONCLUSIONS: Reduction in max SUV following SBRT is associated with local control.

A complement receptor C5a antagonist regulates epithelial to mesenchymal transition and crystallin expression after lens cataract surgery in mice.

PURPOSE: To evaluate the effects of complement employing a mouse model for secondary cataract. METHODS: The role of complement receptor C5a (CD88) was evaluated after cataract surgery in mice. An antagonist specific to C5a receptor was administered intraperitoneally to mice. Epithelial to mesenchymal transition (EMT) was evaluated by alpha-smooth muscle actin (α-SMA) staining and proliferation by bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) incorporation. Gene expression patterns was examined by microarray analysis and quantitative polymerase chain reaction (QPCR). RESULTS: We found that administration of a C5aR antagonist in C57BL/6J mice decreases EMT, as evidenced by α-SMA expression, and cell proliferation. Gene expression by microarray analysis reveals discreet steps of gene regulation in the two major stages that of EMT and lens fiber differentiation in vivo. A hallmark of the microarray analysis is that the antagonist seems to be a novel stage-specific regulator of crystallin genes. At week two, which is marked by lens fiber differentiation genes encoding 12 crystallins and 3 lens-specific structural proteins were severely down-regulated. CONCLUSIONS: These results suggest a possible therapeutic role of an antagonist to C5aR in preventing secondary cataracts after surgery. Also these results suggest that crystallin gene expression can be regulated by pro-inflammatory events in the eye.

In vivo assay of folate receptors in nonfunctional pituitary adenomas with 99mTc-folate SPECT/CT.

UNLABELLED: The objective of this study was to evaluate the in vivo assay of folate receptors in nonfunctional pituitary adenomas using preoperative (99m)Tc-folate SPECT/CT and Western blot analysis (WBA) of surgical specimens as the standard. METHODS: Fifty-six patients (29 men, 27 women; age range, 29-82 y) with clinically nonfunctional pituitary adenomas on MRI underwent preoperative imaging using 666 MBq (18 mCi) of (99m)Tc-folate. SPECT/CT images and whole-body and lateral head planar images were acquired approximately 2 h after injection. Surgical resection took place within a week. WBA on a portion of the excised specimens assessed folate receptor expression in 49 patients. Attenuation-corrected (99m)Tc-folate SPECT/CT images were assessed qualitatively and quantitatively (maximal adenoma counts to background), with WBA as a standard. RESULTS: Integrated CT was useful for uptake localization and assisted region-of-interest placement. Qualitative interpretation of planar imaging yielded a sensitivity of 81% and specificity of 72%. Qualitative SPECT/CT yielded a sensitivity of 94% and specificity of 61%. Receiver-operating-characteristic curve analysis of quantitative uptake yielded a tumor-to-background cutoff ratio of 3.5, with a sensitivity of 81% and specificity of 83%. Scalp uptake yielded consistent results (over the brain, neck, and choroid plexus) for background when SPECT/CT misalignment artifacts were avoided. Detection of pituitary uptake on anterior-posterior and lateral images was hampered by facial uptake, which varied between patients. CONCLUSION: SPECT/CT of (99m)Tc-folate is an accurate method of assaying folate receptors in vivo and may provide a quantitative marker for identifying folate receptor-positive tumors. This method may also prove beneficial in selecting patients for folate-targeted therapy of clinically nonfunctional pituitary adenomas, for which there is currently no medical therapy.

PET lesion segmentation using automated iso-intensity contouring in head and neck cancer.

To improve the objectivity of the integration of positron emission tomography (PET), we used the conformality index (CI) to measure the goodness of fit of a given PET iso-SUV (standardized uptake value) level with the GTV defined on PET (GTV(PET)) and CT (GTV(CT)). Twenty-two datasets involving 20 head and neck cancer patients were identified. GTV(PET) and GTV(CT) were delineated manually.An iso-intensity method was developed to automatically segment GTV(PET-ISO) using (a) SUV and (b) maximum intensity thresholding (% Max), over a range of intensities. For each intensity, GTV(PET-ISO) was compared to GTV(PET) using the conformality index CI(PET) (and, similarly, to GTV(CT) using CICT). Comparing GTV(PET) to GTV(PET-ISO) vs comparing GTV(CT) to GTV(PET-ISO), the average peak CI was 0.68 +/- 0.09 vs 0.49 +/- 0.12 (p < 0.001), the optimum iso-SUV was 2.7 +/- 0.7 vs 2.9 +/- 1.0 (p=0. 253), and the % Max SUV was 21.8% +/- 7.6% vs 23.8% +/- 8.6% (p=0. 310), respectively. The radiation oncologist's volumes corresponded to a lower iso-SUV (3.02 +/- 0.58 vs 4.36 +/- 0.77, p< 0.001) and lower % Max SUV (24.1 +/- 9.1% vs 34.3 +/- 11.2%, p<0.001) than those drawn by the nuclear medicine physician. Though manual editing may still be necessary, PET iso-contouring is one method to improve the objectivity of GTV definition in head and neck cancer patients. Iso-SUV's can also be used to study the differences between PET's role as a nuclear medicine diagnostic test versus a radiation oncology treatment planning tool.

Regeneration according to Spallanzani.

In this report, we elaborate on a letter that Spallanzani wrote to Bonnet reporting his findings on regeneration in worms, snails, tadpoles, and salamanders. The letter (original in French and translated in English; see Supplementary Material, which is available online) was written to discuss whether or not regeneration in these animals supports Bonnet's theory on germs. The letter includes several drawings by Spallanzani, which were not published in the Prodromo, his book on Animal Reproduction. Spallanzani made important observations, which he described with considerable detail, but overall he was unable to confidently support Bonnet's theory. This letter reflects the way of thinking in the 18(th) century that shaped the important scientific fields of regeneration and reproduction.

Pelvic shape and prostate motion: implications for target volume design and analysis of acute toxicity.

OBJECTIVES: To study the impact of pelvic shape on prostate motion and the implications for radiotherapy target design and treatment outcomes. METHODS: A total of 3741 measurements (daily shift moves in the 3 principal directions) on 29 consecutive prostate cancer patients were reviewed. All patients had 3 prostatic fiducials placed and were tracked using kilovoltage on-board imaging. Pelvic shape was categorized into android (n = 21; 2580 measurements) and gynecoid (n = 8; 1161 measurements) (defined geometrically by postoutlet to preoutlet ratio). Multivariate analyses of means/standard deviations in each principal direction were performed using major demographic, disease, anatomic, and treatment factors as covariates. Toxicity rates were compared using Fisher exact test. RESULTS: On simple t test comparisons, no mean/standard deviation reached significance, although there was a nonsignificant (0.38 vs. 0.31 cm, P = 0.083) larger mean antero-posterior (AP) movement in the gynecoid group. On multivariate analyses, gynecoid shape (P = 0.032) significantly predicted for mean AP movement, and gynecoid shape (P = 0.045) significantly predicted for standard deviation of AP movement. Pelvic AP and RL dimensions also correlated with mean and standard movement along the respective axes. There were no differences between rates of acute (GI or GU) toxicity (P = 0.456) between the android and gynecoid groups. CONCLUSIONS: Treatment strategies that do not employ daily motion tracking may require wider planning target volume margins in gynecoid patients. Tracking the prostate daily, as done in our case using fiducials/on-board imaging, can counter differences in pelvic shape to produce similar treatment outcomes.

Case study of anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid (anti-[F-18] FACBC) to guide prostate cancer radiotherapy target design.

PURPOSE OF THE REPORT: Anti-1-amino-3-F-18 fluorocyclobutane-1-carboxylic acid (FACBC) is a novel radiotracer, which has shown some promise for use with positron emission tomography (PET)/computed tomography (CT) for visualizing prostate cancer. Here we describe a case of a prostate cancer patient who underwent radiation treatment and had an FACBC scan obtained as part of a pilot study. METHODS: We explored the potential impact of FACBC on treatment planning. We registered the FACBC acquisition with the PET/CT, which required a simple translation. Then, we did a deformable image registration of the PET/CT with the planning CT-this process allowed the FACBC-defined gross tumor volume (GTVFACBC) to be projected into the planning CT. An intensity-modulated radiotherapy (IMRT) plan (plan A) not including GTVFACBC (with final dose to 81.0 Gy) was generated, as was an IMRT plan including the GTVFACBC to a final dose of 86.4 Gy (plan B). Target coverage and normal tissue dose volume histogram (DVH) endpoints were tabulated. RESULTS: In this particular patient, bladder constraints could not be met on any plan due to anatomic limitations. However, the impact on the rectal DVH could be assessed, and inclusion of the GTVFACBC did permit rectal DVH constraints to be met in plan B while maintaining target coverage and inhomogeneity constraints. CONCLUSION: In our test case, it was feasible to use FACBC to guide IMRT, and highlights the role of deformable image registration of the PET/CT with the planning CT. These findings can guide future studies incorporating FACBC into treatment planning.

A comparative proteomic analysis during urodele lens regeneration.

To examine underlying mechanisms of urodele lens regeneration we have employed a proteomic analysis of 650 proteins involved in several signaling pathways. We compared expression of these proteins between the regeneration-competent dorsal iris and the regeneration-incompetent ventral iris in the newt. After a series of screenings we selected several proteins to evaluate their expression quantitatively on immunoblots. We then used these selected proteins to compare their expression between the dorsal iris of the newt and the iris of the axolotl, another urodele, which does not regenerate the lens. In the newt we find that most proteins are expressed in both dorsal and ventral iris, even though there is differential regulation. Moreover, several of these proteins are expressed in the axolotl iris as well and for some of them their expression is consistent with the regeneration potential.

Automated data mining of a proprietary database system for physician quality improvement.

PURPOSE: Physician practice quality improvement is a subject of intense national debate. This report describes using a software data acquisition program to mine an existing, commonly used proprietary radiation oncology database to assess physician performance. METHODS AND MATERIALS: Between 2003 and 2004, a manual analysis was performed of electronic portal image (EPI) review records. Custom software was recently developed to mine the record-and-verify database and the review process of EPI at our institution. In late 2006, a report was developed that allowed for immediate review of physician completeness and speed of EPI review for any prescribed period. RESULTS: The software extracted >46,000 EPIs between 2003 and 2007, providing EPI review status and time to review by each physician. Between 2003 and 2007, the department EPI review improved from 77% to 97% (range, 85.4-100%), with a decrease in the mean time to review from 4.2 days to 2.4 days. The initial intervention in 2003 to 2004 was moderately successful in changing the EPI review patterns; it was not repeated because of the time required to perform it. However, the implementation in 2006 of the automated review tool yielded a profound change in practice. Using the software, the automated chart review required approximately 1.5 h for mining and extracting the data for the 4-year period. CONCLUSION: This study quantified the EPI review process as it evolved during a 4-year period at our institution and found that automation of data retrieval and review simplified and facilitated physician quality improvement.