Outcomes for Vertebrectomy for Malignancy and Correlation to the Spine Instability Neoplastic Score (SINS): a 10-Year Single-Center Perspective.

OBJECTIVE: The clinical prognostic value of the Spinal Instability Neoplastic Score (SINS), in the context of vertebrectomy for neoplasia, has not yet been established. This retrospective study of 134 patients aims to evaluate the efficacy of the SINS to predict outcomes and survival after vertebrectomy for malignancy. METHODS: The patients were classified into 2 groups: indeterminate stability (SINS 7-12) and unstable (SINS 13-18). Outcomes assessed included survival days after procedure, neurological function (modified Frankel grade), operative time, blood loss, complications, construct failure, and length of inpatient stay. RESULTS: The indeterminate group included 68 patients, whereas the unstable group included 66 patients. No patients were classified as stable (SINS 0-6). The median survival was 225 days (interquartile range, 81-522 days). There was a statistically significant difference (P < 0.001) in survival days after vertebrectomy between the indeterminate group (435 days) and the unstable group (126 days). The majority of patients (119) had a favourable Frankel grade after procedure with no significant difference between SINS groups (P = 0.534). There were no differences in the operative time (234 vs. 210; P = 0.130), inpatient hospital length of stay (10 days vs. 11 days; P = 0.152), complications, or need for intensive care admission (intensive care unit) between the 2 cohorts. There was a statistically significant difference (P = 0.006) for intraoperative blood loss between the indeterminate group (1400 mL) and the unstable group (850 mL). CONCLUSIONS: This study demonstrates a statistically significant increased survival in the indeterminate cohort. These results demonstrate the potential ability of the SINS to act as a clinical prognostic tool with regard to survival time.

Erratum: Spectroscopic Quadrupole Moments in

This corrects the article DOI: 10.1103/PhysRevLett.116.022701.

Spectroscopic Quadrupole Moments in {96,98}Sr: Evidence for Shape Coexistence in Neutron-Rich Strontium Isotopes at N=60.

Neutron-rich {96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60.

(97)(37)Rb(60): The Cornerstone of the Region of Deformation around A ∼ 100 [corrected].

Excited states of the neutron-rich nuclei (97,99)Rb were populated for the first time using the multistep Coulomb excitation of radioactive beams. Comparisons of the results with particle-rotor model calculations provide clear identification for the ground-state rotational band of (97)Rb as being built on the πg(9/2) [431] 3/2(+) Nilsson-model configuration. The ground-state excitation spectra of the Rb isotopes show a marked distinction between single-particle-like structures below N=60 and rotational bands above. The present study defines the limits of the deformed region around A∼100 and indicates that the deformation of (97)Rb is essentially the same as that observed well inside the deformed region. It further highlights the power of the Coulomb-excitation technique for obtaining spectroscopic information far from stability. The (99)Rb case demonstrates the challenges of studies with very short-lived postaccelerated radioactive beams.

Lack of pairing during meiosis triggers multigenerational transgene silencing in Caenorhabditis elegans.

Single-copy transgenes in Caenorhabditis elegans can be subjected to a potent, irreversible silencing process termed small RNA-induced epigenetic silencing (RNAe). RNAe is promoted by the Piwi Argonaute protein PRG-1 and associated Piwi-interacting RNAs (piRNAs), as well as by proteins that promote and respond to secondary small interfering RNA (siRNA) production. Here we define a related siRNA-mediated silencing process, termed "multigenerational RNAe," which can occur for transgenes that are maintained in a hemizygous state for several generations. We found that transgenes that contain either GFP or mCherry epitope tags can be silenced via multigenerational RNAe, whereas a transgene that possesses GFP and a perfect piRNA target site can be rapidly and permanently silenced via RNAe. Although previous studies have shown that PRG-1 is typically dispensable for maintenance of RNAe, we found that both initiation and maintenance of multigenerational RNAe requires PRG-1 and the secondary siRNA biogenesis protein RDE-2. Although silencing via RNAe is irreversible, we found that transgene expression can be restored when hemizygous transgenes that were silenced via multigenerational RNAe become homozygous. Furthermore, multigenerational RNAe was accelerated when meiotic pairing of the chromosome possessing the transgene was abolished. We propose that persistent lack of pairing during meiosis elicits a reversible multigenerational silencing response, which can lead to permanent transgene silencing. Multigenerational RNAe may be broadly relevant to single-copy transgenes used in experimental biology and to shaping the epigenomic landscape of diverse species, where genomic polymorphisms between homologous chromosomes commonly result in unpaired DNA during meiosis.

Shape coexistence in the neutron-deficient even-even (182-188)Hg isotopes studied via coulomb excitation.

Coulomb-excitation experiments to study electromagnetic properties of radioactive even-even Hg isotopes were performed with 2.85 MeV/nucleon mercury beams from REX-ISOLDE. Magnitudes and relative signs of the reduced E2 matrix elements that couple the ground state and low-lying excited states in Hg182-188 were extracted. Information on the deformation of the ground and the first excited 0+ states was deduced using the quadrupole sum rules approach. Results show that the ground state is slightly deformed and of oblate nature, while a larger deformation for the excited 0+ state was noted in Hg182,184. The results are compared to beyond mean field and interacting-boson based models and interpreted within a two-state mixing model. Partial agreement with the model calculations was obtained. The presence of two different structures in the light even-mass mercury isotopes that coexist at low excitation energy is firmly established.

Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans.

Dietary restriction (DR) extends lifespan in a wide variety of species, yet the underlying mechanisms are not well understood. Here we show that the Caenorhabditis elegans HNF4α-related nuclear hormone receptor NHR-62 is required for metabolic and physiologic responses associated with DR-induced longevity. nhr-62 mediates the longevity of eat-2 mutants, a genetic mimetic of dietary restriction, and blunts the longevity response of DR induced by bacterial food dilution at low nutrient levels. Metabolic changes associated with DR, including decreased Oil Red O staining, decreased triglyceride levels, and increased autophagy are partly reversed by mutation of nhr-62. Additionally, the DR fatty acid profile is altered in nhr-62 mutants. Expression profiles reveal that several hundred genes induced by DR depend on the activity of NHR-62, including a putative lipase required for the DR response. This study provides critical evidence of nuclear hormone receptor regulation of the DR longevity response, suggesting hormonal and metabolic control of life span.

Studies of pear-shaped nuclei using accelerated radioactive beams.

There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.

Toxicity, response rates and survival outcomes of induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy for locally advanced esophageal cancer.

OBJECTIVE: Cisplatin-based chemoradiotherapy is standard treatment for locally advanced esophageal and gastroesophageal cancers; however, the optimal chemotherapy regimen remains to be defined. METHODS: Retrospective single institution analysis of toxicities, response rates and survival outcomes in patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated with induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy. Secondary analysis for association of disease control and outcomes with demographic, tumor and treatment factors (including histology). RESULTS: Fifty-three patients were eligible for the present analysis. All patients underwent endoscopic ultrasonography and were either cT3-4 and/or cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4 Gy, range 0-61.2), and 35 patients completed four cycles of chemotherapy as planned (range 1-4). Severe acute toxicities included Grade ≥ 3 neutropenia and esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal) toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7-63), 17 patients were alive (8 without disease) and 36 deceased. Forty patients experienced disease recurrence, with initial loco-regional, distant or both failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival and freedom from failure were 42 and 9%, respectively, without significant difference by histology. CONCLUSIONS: Cisplatin/irinotecan chemoradiotherapy is tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma esophageal cancers.

New type of asymmetric fission in proton-rich nuclei.

A very exotic process of ß-delayed fission of 180Tl is studied in detail by using resonant laser ionization with subsequent mass separation at ISOLDE (CERN). In contrast to common expectations, the fission-fragment mass distribution of the post-ß-decay daughter nucleus 180Hg (N/Z=1.25) is asymmetric. This asymmetry is more surprising since a mass-symmetric split of this extremely neutron-deficient nucleus would lead to two 90Zr fragments, with magic N=50 and semimagic Z=40. This is a new type of asymmetric fission, not caused by large shell effects related to fragment magic proton and neutron numbers, as observed in the actinide region. The newly measured branching ratio for ß-delayed fission of 180Tl is 3.6(7) × 10(-3)%, approximately 2 orders of magnitude larger than in an earlier study.

Discovery of the shape coexisting 0+ state in 32 Mg by a two neutron transfer reaction.

The "island of inversion" nucleus 32 Mg has been studied by a (t, p) two neutron transfer reaction in inverse kinematics at REX-ISOLDE. The shape coexistent excited 0+ state in 32 Mg has been identified by the characteristic angular distribution of the protons of the Δ L=0 transfer. The excitation energy of 1058 keV is much lower than predicted by any theoretical model. The low γ-ray intensity observed for the decay of this 0+ state indicates a lifetime of more than 10 ns. Deduced spectroscopic amplitudes are compared with occupation numbers from shell-model calculations.

Cisplatin/Irinotecan versus carboplatin/paclitaxel as definitive chemoradiotherapy for locoregionally advanced esophageal cancer.

OBJECTIVE: To compare toxicities, disease control, and survival outcomes for patients treated with either cisplatin/irinotecan versus carboplatin/paclitaxel concurrent chemoradiotherapy for locally advanced esophageal cancer. METHODS: Single-institution retrospective comparison between treatment groups: the cisplatin/irinotecan group was treated with 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy, whereas the carboplatin/paclitaxel group began with chemoradiotherapy followed by 2 additional cycles of chemotherapy. Acute toxicities, response rates, disease control, survival outcomes, and patterns of failure were compared between the groups. RESULTS: Between January 2000 and December 2007, 57 patients were identified for inclusion in the present study (38 cisplatin/irinotecan and 19 carboplatin/paclitaxel). Groups were well-balanced by clinical-, pathologic-, staging-, and treatment-related factors. Thirty-five patients (92%) in the cisplatin/irinotecan group and 18 patients (95%) in the carboplatin/paclitaxel group completed the concurrent phase of chemoradiotherapy. There were no significant differences in hematologic or nonhematologic toxicities between the groups. At a median survivor follow-up of 37.6 months (range: 7.3-59.3 months) for the entire population, 22 patients were alive (16 without evidence of disease). The 3-year overall survival estimates was 19.7% for the cisplatin/irinotecan group versus 56.1% for the carboplatin/paclitaxel group (P = 0.022). Estimated 3-year cancer-specific survivals were 24.6% for the cisplatin/irinotecan group versus 59.3% for the carboplatin/paclitaxel group (P = 0.033). CONCLUSION: Concurrent chemoradiotherapy with carboplatin/paclitaxel is well-tolerated and provided superior overall and disease-specific survival compared with cisplatin/irinotecan chemoradiotherapy in the present study population. Further investigation is warranted.

Magnetic dipole moment of (57,59)Cu measured by in-gas-cell laser spectroscopy.

For the first time, in-gas-cell laser spectroscopy study of the (57,59,63,65)Cu isotopes has been performed using the 244.164 nm optical transition from the atomic ground state of copper. The nuclear magnetic dipole moments for (57,59,65)Cu relative to that of (63)Cu have been extracted. The new value for (57)Cu of mu((57)Cu) = +2.582(7)mu(N) is in strong disagreement with the previous literature value but in good agreement with recent theoretical and systematic predictions.

Cortisol interferes with the estradiol-induced surge of luteinizing hormone in the ewe.

Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was approximately 1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

Interplay between single-particle and collective effects in the odd-A Cu isotopes beyond N=40.

Collective properties of the low-lying levels in the odd-A 67-73Cu were investigated by Coulomb excitation with radioactive beams. The beams were produced at ISOLDE and postaccelerated by REX-ISOLDE up to 2.99 MeV/u. In 67,69Cu, low-lying 1/2(-), 5/2(-), and 7/2(-) states were populated. In 71,73Cu, besides the known transitions deexciting the single-particle-like 5/2(-) and core-coupled 7/2(-) levels, gamma rays of 454 and 135 keV, respectively, were observed for the first time. Based on a reanalysis of beta-decay work and comparison with the systematics, a spin 1/2(-) is suggested for these excited states. Three B(E2) values were determined in each of the four isotopes. The results indicate a significant change in the structure of the odd-A Cu isotopes beyond N=40 where single-particle-like and collective levels are suggested to coexist at very low excitation energies.

Film dosimetry for radiotherapy treatment planning verification of a 6 MV tangential breast irradiation.

Film dosimetry has been applied to measure relative dose distributions in an anthropomorphic polystyrene breast phantom having cork lungs, simulating a radiation therapy treatment with 6 MV opposing tangential beams. Measured relative dose distributions showed good reproducibility (about 1.5%, 1 SD) and good agreement (< 2%) with calculations performed with a three-dimensional treatment planning system. These results demonstrate that film dosimetry is a useful tool for treatment planning verification.

Should inhomogeneity corrections be applied during treatment planning of tangential breast irradiation?

Due to the inclusion of lung tissue in the treatment volume, some parts of the breast will get a higher dose during tangential breast irradiation because of the lower lung density. Data on the accuracy of dose calculation algorithms, investigated by phantom measurements, determinations of the geometry and density of the actual lung in the patient and the results of in vivo dose measurements, are presented. From this information it can be concluded that a lung correction varying between about 3% and 7% is needed but its magnitude is slightly overpredicted in a number of commercial treatment planning systems. Because this increase in dose is already in a high dose region, it is recommended that inhomogeneity corrections should be applied during tangential breast irradiation.

Three-dimensional dose distribution of tangential breast treatment: a national dosimetry intercomparison.

From August 1990 to February 1991, a dosimetry intercomparison of breast treatment was performed at all 21 radiotherapy centres in The Netherlands. The absorbed dose was measured in three planes in a breast phantom during tangential breast irradiation, according to a prescribed technique. The beam energy could be chosen by the radiotherapy centre as normally applied for this type of "patient", and varied between 60Co and 8 MV X rays. The dose measured by the visiting team in 22 points inside the phantom was compared with the dose calculated by the institution using their local treatment planning system. In the institutions the mean ratio (the mean value of the ratios of the absolute calculated dose and the measured absolute dose in the 22 points) varied between 0.92 and 1.08 with an overall mean ratio of 1.04. There was no significant difference in this ratio between the three planes in a particular institution. In the isocentre the mean ratio of calculated and measured dose was 1.021 with a SD of 0.028, i.e. the algorithms in the six different commercial treatment planning systems calculate the dose generally somewhat too high. In order to explain the results, a measurement of the output under reference conditions was performed at each treatment unit. The mean ratio of the dose stated by the institution and the dose measured by the visiting team was 1.011 with a SD of 0.015 with a maximum deviation of 0.040. This small deviation explains therefore only part of the variation in the ratio of calculated and measured dose for tangential breast irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality assurance of the EORTC trial 22881/10882: "assessment of the role of the booster dose in breast conserving therapy": the Dummy Run. EORTC Radiotherapy Cooperative Group.

The EORTC trial 22881/10882 is a randomised trial with the aim to assess the role of the boost dose in breast conserving therapy in stage I and II breast cancer. In order to detect potential protocol deviations concerning irradiation technique and in the dose specification procedure of participating institutions before actual patient accrual, a Dummy Run was performed. Three transverse sections of a patient were sent to 16 participating institutions with a request to make a three-plane treatment plan according to the protocol prescriptions. A treatment chart and beam data were also requested for recalculation of the dose. Additional information was asked in a questionnaire. On evaluation, the techniques differed considerably with respect to photon beam energy, varying between 60Co gamma-rays and 8 MV X-rays, and the use of wedge filters. Two institutions did not apply wedges, whereas wedge angles in the other institutions varied between 6 degrees and 45 degrees. Twelve institutions used collimator rotation and/or a table wedge to diminish the amount of irradiated lung volume. The dose was specified in a point according to the protocol prescription in 11 institutions and to the 90, 95 or 100% isodose curve in four. Twelve institutions applied lung density corrections during treatment planning, while nine reported problems with their planning system in off-axis dose distribution calculation and/or the simulation of collimator rotation. Recalculation of the dose at the isocentre showed agreement within 2% compared with the stated dose. The dose reported in the tumour excision area varied between 93 and 100%.(ABSTRACT TRUNCATED AT 250 WORDS)