Growth and population structure of Lodoicea maldivica in natural stands in Seychelles.

We monitored leaf production in seedlings, trunkless juvenile, immature, and mature male and female plants of the dioecious palm, Lodoicea maldivica, and studied how internode length changed with trunk height. The fieldwork was conducted in closed forest on Praslin Island and degraded forest on Curieuse Island. Data on numbers of leaves produced and rates of leaf production were used to estimate plant age. On Praslin, the interval between successive leaves increased from 0.47/0.52 years in male/female plants to 4.2 years in seedlings, and on Curieuse from 0.41/0.49 to 2.3 years. Estimated leaf lifespan was 6.4-6.8 years in mature palms and much longer in seedlings and juveniles. On Praslin, internode length increased from the base of the trunk to a mean of 14 cm at leaf 21, before declining to 2.75 cm above leaf 100. Mean internode length of the smaller palms on Curieuse was 1.9 cm and varied little with height. Plants at the same development stage varied widely in age. On Praslin, median time to maturity was 77 (range: 32-209) and on Curieuse 83 (31-191) years. The tallest palms on Praslin (28.4 m trunk height) and Curieuse (8 m) were estimated at 442 and 232 years old, respectively. The ageing method was used to interpret height data of different populations. All showed a marked decline in regeneration in the 19th or early 20th centuries, probably caused by fires. We conclude that slow growth makes this species very vulnerable to disturbance, especially from fire.

Testing CPT symmetry in ortho-positronium decays with positronium annihilation tomography.

Charged lepton system symmetry under combined charge, parity, and time-reversal transformation (CPT) remains scarcely tested. Despite stringent quantum-electrodynamic limits, discrepancies in predictions for the electron-positron bound state (positronium atom) motivate further investigation, including fundamental symmetry tests. While CPT noninvariance effects could be manifested in non-vanishing angular correlations between final-state photons and spin of annihilating positronium, measurements were previously limited by knowledge of the latter. Here, we demonstrate tomographic reconstruction techniques applied to three-photon annihilations of ortho-positronium atoms to estimate their spin polarisation without magnetic field or polarised positronium source. We use a plastic-scintillator-based positron-emission-tomography scanner to record ortho-positronium (o-Ps) annihilations with single-event estimation of o-Ps spin and determine the complete spectrum of an angular correlation operator sensitive to CPT-violating effects. We find no violation at the precision level of 10-4, with an over threefold improvement on the previous measurement.

Optimisation of the event-based TOF filtered back-projection for online imaging in total-body J-PET.

We perform a parametric study of the newly developed time-of-flight (TOF) image reconstruction algorithm, proposed for the real-time imaging in total-body Jagiellonian PET (J-PET) scanners. The asymmetric 3D filtering kernel is applied at each most likely position of electron-positron annihilation, estimated from the emissions of back-to-back γ-photons. The optimisation of its parameters is studied using Monte Carlo simulations of a 1-mm spherical source, NEMA IEC and XCAT phantoms inside the ideal J-PET scanner. The combination of high-pass filters which included the TOF filtered back-projection (FBP), resulted in spatial resolution, 1.5 times higher in the axial direction than for the conventional 3D FBP. For realistic 10-minute scans of NEMA IEC and XCAT, which require a trade-off between the noise and spatial resolution, the need for Gaussian TOF kernel components, coupled with median post-filtering, is demonstrated. The best sets of 3D filter parameters were obtained by the Nelder-Mead minimisation of the mean squared error between the resulting and reference images. The approach allows training the reconstruction algorithm for custom scans, using the IEC phantom, when the temporal resolution is below 50 ps. The image quality parameters, estimated for the best outcomes, were systematically better than for the non-TOF FBP.

Simulating NEMA characteristics of the modular total-body J-PET scanner-an economic total-body PET from plastic scintillators.

The purpose of the presented research is estimation of the performance characteristics of the economic total-body Jagiellonian-PET system (TB-J-PET) constructed from plastic scintillators. The characteristics are estimated according to the NEMA NU-2-2018 standards utilizing the GATE package. The simulated detector consists of 24 modules, each built out of 32 plastic scintillator strips (each with cross section of 6 mm times 30 mm and length of 140 or 200 cm) arranged in two layers in regular 24-sided polygon circumscribing a circle with the diameter of 78.6 cm. For the TB-J-PET with an axial field-of-view (AFOV) of 200 cm, a spatial resolutions (SRs) of 3.7 mm (transversal) and 4.9 mm (axial) are achieved. The noise equivalent count rate (NECR) peak of 630 kcps is expected at 30 kBq cc-1. Activity concentration and the sensitivity at the center amounts to 38 cps kBq-1. The scatter fraction (SF) is estimated to 36.2 %. The values of SF and SR are comparable to those obtained for the state-of-the-art clinical PET scanners and the first total-body tomographs: uExplorer and PennPET. With respect to the standard PET systems with AFOV in the range from 16 to 26 cm, the TB-J-PET is characterized by an increase in NECR approximately by factor of 4 and by the increase of the whole-body sensitivity by factor of 12.6 to 38. The time-of-flight resolution for the TB-J-PET is expected to be at the level of CRT = 240 ps full width at half maximum. For the TB-J-PET with an AFOV of 140 cm, an image quality of the reconstructed images of a NEMA IEC phantom was presented with a contrast recovery coefficient and a background variability parameters. The increase of the whole-body sensitivity and NECR estimated for the TB-J-PET with respect to current commercial PET systems makes the TB-J-PET a promising cost-effective solution for the broad clinical applications of total-body PET scanners. TB-J-PET may constitute an economic alternative for the crystal TB-PET scanners, since plastic scintillators are much cheaper than BGO or LYSO crystals and axial arrangement of the strips significantly reduces the costs of readout electronics and SiPMs.

3D TOF-PET image reconstruction using total variation regularization.

In this paper we introduce a semi-analytic algorithm for 3-dimensional image reconstruction for positron emission tomography (PET). The method consists of the back-projection of the acquired data into the most likely image voxel according to time-of-flight (TOF) information, followed by the filtering step in the image space using an iterative optimization algorithm with a total variation (TV) regularization. TV regularization in image space is more computationally efficient than usual iterative optimization methods for PET reconstruction with full system matrix that use TV regularization. The efficiency comes from the one-time TOF back-projection step that might also be described as a reformatting of the acquired data. An important aspect of our work concerns the evaluation of the filter operator of the linear transform mapping an original radioactive tracer distribution into the TOF back-projected image. We obtain concise, closed-form analytical formula for the filter operator. The proposed method is validated with the Monte Carlo simulations of the NEMA IEC phantom using a one-layer, 50 cm-long cylindrical device called Jagiellonian PET scanner. The results show a better image quality compared with the reference TOF maximum likelihood expectation maximization algorithm.

Performance assessment of the 2 γpositronium imaging with the total-body PET scanners.

PURPOSE: In living organisms, the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511 keV photons. In this article, we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include the (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2γ annihilations and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. METHODS: Simulations are conducted assuming that radiopharmaceutical is labeled with 44Sc isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution, the four cases were considered assuming that CRT is equal to 500 ps, 140 ps, 50 ps, and 10 ps. RESULTS: The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences (2γ+γprompt) is larger by a factor of 13.5 (for LYSO PET) and by factor of 5.2 (for plastic PET) with respect to the sensitivity for the standard 2γ imaging by LYSO PET scanners with AFOV = 20 cm. The spatial resolution of the ortho-positronium image is comparable with the resolution achievable when using TOF-FBP algorithms already for CRT = 50 ps. For the 20-min scan, the resolution better than 20 ps is expected for the mean ortho-positronium lifetime image determination. CONCLUSIONS: Ortho-positronium mean lifetime imaging based on the annihilations into two photons and prompt gamma is shown to be feasible with the advent of the high sensitivity total-body PET systems and time resolution of the order of tens of picoseconds.

Estimating relationship between the time over threshold and energy loss by photons in plastic scintillators used in the J-PET scanner.

PURPOSE: The time-over-threshold (TOT) technique is being used widely due to itsimplications in developing the multi-channel readouts, mainly when fast signal processing is required. Using the TOT technique, as a measure of energy loss instead of charge integration methods, significantly reduces the signal readout costs by combining the time and energy information. Therefore, this approach can potentially be utilized in J-PET tomograph which is built from plastic scintillators characterized by fast light signals. The drawback in adopting this technique lies in the non-linear correlation between input energy loss and TOT of the signal. The main motivation behind this work is to develop the relationship between TOT and energy loss and validate it by the J-PET tomograph setup. METHODS: The experiment was performed using a 22Na beta emitter source placed in the center of the J-PET tomograph. This isotope produces photons of two different energies: 511 keV photons from the positron annihilation (direct annihilation or through the formation of a para-positronium atom or pick-off process of ortho-positronium atoms) and a 1275 keV prompt photon. This allows the study of the correlation between TOT values and energy loss for energy ranges up to 1000 keV. Since the photon interacts predominantly via Compton scattering inside the plastic scintillator, there is no direct information of the energy deposition. However, using the J-PET geometry, one can measure the scattering angle of the interacting photon. Since the 22Na source emits photons of two different energies, it is necessary to know unambiguously the energy of incident photons and their corresponding scattering angles in order to estimate energy deposition. In summary, this work presents a dedicated algorithm developed to tag photons of different energies and studying their scattering angles to calculate the energy deposition by the interacting photons. RESULTS: A new method was elaborated to measure the energy loss by photons interacting with plastic scintillators used in the J-PET tomograph. We find the relationship between the energy loss and TOT is non-linear and can be described by the functions TOT = A0 + A1 * ln(E dep + A2) + A3 * (ln(E dep + A2))2 and TOT = A0 - A1 * A2[Formula: see text]. In addition, we also introduced a theoretical model to calculate the TOT as a function of energy loss in plastic scintillators. CONCLUSIONS: A relationship between TOT and energy loss by photons interacting inside the plastic scintillators used in J-PET scanner is established for a deposited energy range of 100-1000 keV.

Feasibility study of the positronium imaging with the J-PET tomograph.

A detection system of the conventional PET tomograph is set-up to record data from [Formula: see text] annihilation into two photons with energy of 511 keV, and it gives information on the density distribution of a radiopharmaceutical in the body of the object. In this paper we explore the possibility of performing the three gamma photons imaging based on ortho-positronium annihilation, as well as the possibility of positronium mean lifetime imaging with the J-PET tomograph constructed from plastic scintillators. For this purposes simulations of the ortho-positronium formation and its annihilation into three photons were performed taking into account distributions of photons' momenta as predicted by the theory of quantum electrodynamics and the response of the J-PET tomograph. In order to test the proposed ortho-positronium lifetime image reconstruction method, we concentrate on the decay of the ortho-positronium into three photons and applications of radiopharmaceuticals labeled with isotopes emitting a prompt gamma. The proposed method of imaging is based on the determination of hit-times and hit-positions of registered photons which enables the reconstruction of the time and position of the annihilation point as well as the lifetime of the ortho-positronium on an event-by-event basis. We have simulated the production of the positronium in point-like sources and in a cylindrical phantom composed of a set of different materials in which the ortho-positronium lifetime varied from 2.0 ns to 3.0 ns, as expected for ortho-positronium created in the human body. The presented reconstruction method for total-body J-PET like detector allows to achieve a mean lifetime resolution of ∼40 ps. Recent positron annihilation lifetime spectroscopy measurements of cancerous and healthy uterine tissues show that this sensitivity may allow to study the morphological changes in cell structures.

Estimating the NEMA characteristics of the J-PET tomograph using the GATE package.

A novel whole-body positron emission tomography (PET) system based on plastic scintillators is developed by the J-PET Collaboration. It consists of plastic scintillator strips arranged axially in the form of a cylinder, allowing the cost-effective construction of the total-body PET system. In order to determine the properties of the scanner prototype and optimize its geometry, advanced computer simulations were performed using the GATE (Geant4 application for tomographic emission) software. The spatial resolution, sensitivity, scatter fraction and noise equivalent count rate were estimated according to the National Electrical Manufacturers Association norm, as a function of the length of the tomograph, the number of detection layers, the diameter of the tomographic chamber and for various types of applied readout. For the single-layer geometry with a diameter of 85 cm, a strip length of 100 cm, a cross-section of 4 mm × 20 mm and silicon photomultipliers with an additional layer of wavelength shifter as the readout, the spatial resolution (full width at half maximum) in the centre of the scanner is equal to 3 mm (radial, tangential) and 6 mm (axial). For the analogous double-layer geometry with the same readout, diameter and scintillator length, with a strip cross-section of 7 mm × 20 mm, a noise equivalent count rate peak of 300 kcps was reached at 40 kBq cc-1 activity concentration, the scatter fraction is estimated to be about 35% and the sensitivity at the centre amounts to 14.9 cps kBq-1. Sensitivity profiles were also determined.

Evaluation of Single-Chip, Real-Time Tomographic Data Processing on FPGA SoC Devices.

A novel approach to tomographic data processing has been developed and evaluated using the Jagiellonian positron emission tomography scanner as an example. We propose a system in which there is no need for powerful, local to the scanner processing facility, capable to reconstruct images on the fly. Instead, we introduce a field programmable gate array system-on-chip platform connected directly to data streams coming from the scanner, which can perform event building, filtering, coincidence search, and region-of-response reconstruction by the programmable logic and visualization by the integrated processors. The platform significantly reduces data volume converting raw data to a list-mode representation, while generating visualization on the fly.

Feasibility studies of the polarization of photons beyond the optical wavelength regime with the J-PET detector.

J-PET is a detector optimized for registration of photons from the electron-positron annihilation via plastic scintillators where photons interact predominantly via Compton scattering. Registration of both primary and scattered photons enables to determinate the linear polarization of the primary photon on the event by event basis with a certain probability. Here we present quantitative results on the feasibility of such polarization measurements of photons from the decay of positronium with the J-PET and explore the physical limitations for the resolution of the polarization determination of 511 keV photons via Compton scattering. For scattering angles of about 82 ∘ (where the best contrast for polarization measurement is theoretically predicted) we find that the single event resolution for the determination of the polarization is about 40 ∘ (predominantly due to properties of the Compton effect). However, for samples larger than ten thousand events the J-PET is capable of determining relative average polarization of these photons with the precision of about few degrees. The obtained results open new perspectives for studies of various physics phenomena such as quantum entanglement and tests of discrete symmetries in decays of positronium and extend the energy range of polarization measurements by five orders of magnitude beyond the optical wavelength regime.

Calculation of the time resolution of the J-PET tomograph using kernel density estimation.

In this paper we estimate the time resolution of the J-PET scanner built from plastic scintillators. We incorporate the method of signal processing using the Tikhonov regularization framework and the kernel density estimation method. We obtain simple, closed-form analytical formulae for time resolution. The proposed method is validated using signals registered by means of the single detection unit of the J-PET tomograph built from a 30 cm long plastic scintillator strip. It is shown that the experimental and theoretical results obtained for the J-PET scanner equipped with vacuum tube photomultipliers are consistent.

A feasibility study of ortho-positronium decays measurement with the J-PET scanner based on plastic scintillators.

We present a study of the application of the Jagiellonian positron emission tomograph (J-PET) for the registration of gamma quanta from decays of ortho-positronium (o-Ps). The J-PET is the first positron emission tomography scanner based on organic scintillators in contrast to all current PET scanners based on inorganic crystals. Monte Carlo simulations show that the J-PET as an axially symmetric and high acceptance scanner can be used as a multi-purpose detector well suited to pursue research including e.g. tests of discrete symmetries in decays of ortho-positronium in addition to the medical imaging. The gamma quanta originating from o-Ps decay interact in the plastic scintillators predominantly via the Compton effect, making the direct measurement of their energy impossible. Nevertheless, it is shown in this paper that the J-PET scanner will enable studies of the [Formula: see text] decays with angular and energy resolution equal to [Formula: see text] and [Formula: see text], respectively. An order of magnitude shorter decay time of signals from plastic scintillators with respect to the inorganic crystals results not only in better timing properties crucial for the reduction of physical and instrumental background, but also suppresses significantly the pile-ups, thus enabling compensation of the lower efficiency of the plastic scintillators by performing measurements with higher positron source activities.

Time resolution of the plastic scintillator strips with matrix photomultiplier readout for J-PET tomograph.

Recent tests of a single module of the Jagiellonian Positron Emission Tomography system (J-PET) consisting of 30 cm long plastic scintillator strips have proven its applicability for the detection of annihilation quanta (0.511 MeV) with a coincidence resolving time (CRT) of 0.266 ns. The achieved resolution is almost by a factor of two better with respect to the current TOF-PET detectors and it can still be improved since, as it is shown in this article, the intrinsic limit of time resolution for the determination of time of the interaction of 0.511 MeV gamma quanta in plastic scintillators is much lower. As the major point of the article, a method allowing to record timestamps of several photons, at two ends of the scintillator strip, by means of matrix of silicon photomultipliers (SiPM) is introduced. As a result of simulations, conducted with the number of SiPM varying from 4 to 42, it is shown that the improvement of timing resolution saturates with the growing number of photomultipliers, and that the [Formula: see text] configuration at two ends allowing to read twenty timestamps, constitutes an optimal solution. The conducted simulations accounted for the emission time distribution, photon transport and absorption inside the scintillator, as well as quantum efficiency and transit time spread of photosensors, and were checked based on the experimental results. Application of the [Formula: see text] matrix of SiPM allows for achieving the coincidence resolving time in positron emission tomography of [Formula: see text]0.170 ns for 15 cm axial field-of-view (AFOV) and [Formula: see text]0.365 ns for 100 cm AFOV. The results open perspectives for construction of a cost-effective TOF-PET scanner with significantly better TOF resolution and larger AFOV with respect to the current TOF-PET modalities.

Comparative study of different matrix/solvent systems for the analysis of crude lyophilized microalgal preparations using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

RATIONALE: Due to increases in greenhouse gas emissions, it is necessary to explore renewable sources of energy. Interesting alternatives are biofuels derived from microalgae. One challenge is the development of a detailed microalgae database compiling species identifications and characterizations that would facilitate microalgae selection for biomass production. Mass spectrometric (MS) analysis using a matrix-assisted laser desorption/ionization (MALDI) source is an advanced technique that enables advancement in this biological area. In this work a MALDI time-of-flight (TOF)MS method for the rapid identification of proteins in whole cells of selected microalgae species was studied. Furthermore, the efficiency of different matrix and solvent systems was tested. MS analyses were performed using an UltrafleXtreme MALDI-TOF mass spectrometer operating in linear positive ion mode. METHODS: Mass spectra were acquired in a mass range from 4000 to 20,000 Da with ions generated from Smartbeam laser irradiation using a frequency of 2000 Hz, a PIE 100 ns and a lens 7 kV. The voltage was 25 kV for the first ion source and 23 kV for the second. Each spectrum was generated by averaging of 10,000 laser shots and the laser irradiance was set at 95-100%. RESULTS: Similar mass spectra were obtained for all matrices (SA, HCCA, DHB and sDHB); however, the use of the sDHB matrix resulted in spectrum profiles with a greater amount number of proteins, a better signal/noise (S/N) ratio and higher intensities for the majority of microalgae analyzed. Trifluoroacetic acid (TFA) content was also studied and the best results in terms of S/N ratio, number of proteins and signal intensities were obtained with 0.1% TFA in the matrix solvent. The addition of isopropanol did not produce improvement in the quality of spectrum profiles. CONCLUSIONS: Therefore, the optimal matrix for the analysis of protein from intact microalgae cells is sDHB with TA50 as the matrix solvent and without isopropanol. These conditions allow the acquisition of high quality spectrum profiles.

Reliability of the cervical vertebrae maturation (CVM) method.

OBJECTIVE: To assess the reliability of the cervical vertebrae maturation method (CVM). BACKGROUND: Skeletal maturity estimation can influence the manner and time of orthodontic treatment. The CVM method evaluates skeletal growth on the basis of the changes in the morphology of cervical vertebrae C2, C3, C4 during growth. These vertebrae are visible on a lateral cephalogram, so the method does not require an additional radiograph. METHODS: In this website based study, 10 orthodontists with a long clinical practice (3 routinely using the method - "Routine user - RU" and 7 with less experience in the CVM method - "Non-Routine user - nonRU") rated twice cervical vertebrae maturation with the CVM method on 50 cropped scans of lateral cephalograms of children in circumpubertal age (for boys: 11.5 to 15.5 years; for girls: 10 to 14 years). Kappa statistics (with lower limits of 95% confidence intervals (CI)) and proportion of complete agreement on staging was used to evaluate intra- and inter-assessor agreement. RESULTS: The mean weighted kappa for intra-assessor agreement was 0.44 (range: 0.30-0.64; range of lower limits of 95% CI: 0.12-0.48) and for inter-assessor agreement was 0.28 (range: -0.01-0.58; range of lower limits of 95% CI: -0.14-0.42). The mean proportion of identical scores assigned by the same assessor was 55.2 %(range: 44-74 %) and for different pairs of assessors was 42 % (range: 16-68 %). CONCLUSIONS: The reliability of the CVM method is questionable and if orthodontic treatment should be initiated relative to the maximum growth, the use of additional biologic indicators should be considered (Tab. 4, Fig. 1, Ref. 24).

Sex determination based on the analysis of a contemporary Polish population's palatine bones: a computed tomography study of 1,200 patients.

BACKGROUND: The aims of the present study were to assess whether the hard palate reveals any measurable sex-related differences, and to create a mathematical model which would differentiate between males and females using hard palate measurements alone. MATERIALS AND METHODS: The present study was conducted on 1,200 archived sinus computed tomography (CT) scans. Each cranial measurement was taken twice by the same observer, and in cases of any discrepancies, the mean of the two values was recorded. Twenty per cent of randomly chosen samples were re-measured by an observer who did not partake in assessing the samples the first time. Logistic regression was used to derivate two mathematical formulas which would calculate the probability of a skull being male. RESULTS: The studied group comprised 1,200 head CT's (627 female; 52.3%). The mean age of the group was 43.5 ± 17.4 years - no age difference between sexes was noted (p = 0.37). All of the performed measurements were significantly (p < 0.0001) larger in males than in females. The mathematical formula based on the "orale-spina nasalis posterior" (O-SNP) distance alone had a reliability rate of 68.35%. The equation based on the depth of the right greater palatine canal (GPC), the O-SNP distance and the anterior width of the palatal arch (AWPA) had a reliability rate of 78.37%. CONCLUSIONS: The most prominent sexually dimorphic parameters were the O-SNP, the GPC depth and the AWPA. The mathematical models presented in the current study can be used to successfully distinguish between sexes during forensic examination.

Inflammatory myofibroblastic tumour: a rare entity with wide differential diagnosis.

Inflammatory myofibroblastic tumour (IMT) is a rare, distinctive mesenchymal neoplasm. Grossly, it appears as a circumscribed mass with a rubbery to firm cut surface. Microscopically, it is characterized by a spindle cell proliferation within a myxoid stroma with admixed plasma cells, lymphocytes and eosinophils. Immunohistochemical staining is usually positive for vimentin, smooth muscle actin (SMA) and anaplastic lymphoma kinase (ALK). ALK gene rearrangement is present in approximately 50-70% IMTs. The standard treatment is surgical resection, and it is essential to differentiate IMT from benign and malignant mimickers so that appropriate therapy may be provided. Clinical and radiological follow-up is required to detect recurrence.

Histological evaluation of papillary lesions of the breast from needle biopsy to the excised specimen: a single institutional experience.

BACKGROUND: The assessment and categorization of papillary lesions remains one of the most challenging areas in breast pathology. We evaluated the histological follow-up of papillary lesions of the breast from needle core biopsy to final excision to determine whether these lesions warrant excision, irrespective of histologic subtype. STUDY DESIGN: A total of 91 needle core biopsies from the breast diagnosed as "papillary lesions" at our institution from January 2001 to June 2011 were included in the study. Twenty-nine of these (mean patient age 54.93 +/- 12.5 SD) were reported as benign papillary lesions, and the remaining 62 (mean patient age 61.98 +/- 15.20 SD) were diagnosed as either atypical papillary lesions (17 cases) or malignant papillary lesions (45 cases). RESULTS. Of the 29 needle core biopsies reported as benign, 19 cases (65.5%) were diagnosed as benign and three (10.3%) were diagnosed as malignant on follow-up. The remaining seven cases did not proceed to excision. Sixty-two of the 91 cases were given a diagnosis of either atypical papillary lesion or malignant papillary lesion on needle core biopsy. Of the 45 cases initially diagnosed as malignant, 44 (97.7%) were eventually deemed malignant and one atypical ductal hyperplasia (ADH) was found upon excision. The initial diagnosis of atypical papillary lesion was rendered in 17 cases, of which 10 turned out to be malignant, five ADH, and two benign on excision. CONCLUSION: We conclude that if a benign papillary lesion is present on initial needle core biopsy, then the probability of malignancy is high (10.3%) on the final excision. Similarly, all malignant papillary lesions diagnosed on needle core biopsy should be excised due to the very high likelihood (97.7%) of a diagnosis of malignancy on final excision. Based on our results, we suggest surgical excision of any papillary lesion diagnosed on needle core biopsy.

Regulation of transcription of hypoxia-inducible factor-1α (HIF-1α) by heat shock factors HSF2 and HSF4.

Hypoxia-inducible factor-1α (HIF-1α) is a principal regulator of angiogenesis and other cellular responses to hypoxic stress in both normal and tumor cells. To identify novel mechanisms that regulate expression of HIF-1α, we designed a genome-wide screen for expressed sequence tags (ESTs) that when transcribed in the antisense direction increase production of the HIF-1α target, vascular endothelial growth factor (VEGF), in human breast cancer cells. We discovered that heat shock factor (HSF) proteins 2 and 4-which previously have been implicated in the control of multiple genes that modulate cell growth and differentiation and protect against effects of environmental and cellular stresses-function together to maintain a steady state level of HIF-1α transcription and VEGF production in these cells. We show both HSFs bind to discontinuous heat shock element (HSE) sequences we identified in the HIF-1α promoter region and that downregulation of either HSF activates transcription of HIF-1α. We further demonstrate that HSF2 and HSF4 displace each other from HSF/HSE complexes in the HIF-1α promoter so that HIF-1α transcription is also activated by overexpression of either HSFs. These results argue that HSF2 and HSF4 regulate transcription of HIF-1α and that a critical balance between these HSF is required to maintain HIF-α expression in a repressed state. Our findings reveal a previously unsuspected role for HSFs in control of VEGF and other genes activated by canonical HIF-1α-mediated signaling.