Beam Energy and Centrality Dependence of Direct-Photon Emission from Ultrarelativistic Heavy-Ion Collisions.

The PHENIX collaboration presents first measurements of low-momentum (0.41 GeV/c) direct-photon yield dN_{γ}^{dir}/dη is a smooth function of dN_{ch}/dη and can be well described as proportional to (dN_{ch}/dη)^{α} with α≈1.25. This scaling behavior holds for a wide range of beam energies at the Relativistic Heavy Ion Collider and the Large Hadron Collider, for centrality selected samples, as well as for different A+A collision systems. At a given beam energy, the scaling also holds for high p_{T} (>5 GeV/c), but when results from different collision energies are compared, an additional sqrt[s_{NN}]-dependent multiplicative factor is needed to describe the integrated-direct-photon yield.

Measurements of Elliptic and Triangular Flow in High-Multiplicity 3He+Au Collisions at √(s(NN))=200 GeV.

We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity (3)He+Au collisions at √(s(NN))=200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in (3)He+Au and in p+p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the (3)He+Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d+Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three (3)He nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.

Medium modification of jet fragmentation in Au+Au collisions at √[s(NN)]=200 GeV measured in direct photon-hadron correlations.

The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at √[s(NN)]=200 GeV. The p(T) of the photon is an excellent approximation to the initial p(T) of the jet and the ratio z(T)=p(T)(h)/p(T)(γ) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p. I(AA), the ratio of hadron yield opposite the photon in Au+Au to that in p+p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high z(T). The associated hadron yield at low z(T) is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.

Prognostic role for diffusion-weighted imaging of pediatric optic pathway glioma.

Optic pathway glioma (OPG) has an unpredictable course, with poor correlation between conventional imaging features and tumor progression. We investigated whether diffusion-weighted MRI (DWI) predicts the clinical behavior of these tumors. Twelve children with OPG (median age 2.7 years; range 0.4-6.2 years) were followed for a median 4.4 years with DWI. Progression-free survival (time to requiring therapy) was compared between tumors stratified by apparent diffusion coefficient (ADC) from initial pre-treatment scans. Tumors with baseline ADC greater than 1,400 × 10(-6) mm(2)/s required treatment earlier than those with lower ADC (log-rank p = 0.002). In some cases, ADC increased leading up to treatment, and declined following treatment with surgery, chemotherapy, or radiation. Baseline ADC was higher in tumors that eventually required treatment (1,562 ± 192 × 10(-6) mm(2)/s), compared with those conservatively managed (1,123 ± 114 × 10(-6) mm(2)/s) (Kruskal-Wallis test p = 0.013). Higher ADC predicted earlier tumor progression in this cohort and in some cases declined after therapy. Evaluation of OPG with DWI may therefore be useful for predicting tumor behavior and assessing treatment response.

A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene.

Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.

Measurement of direct photons in Au+Au collisions at √(s(NN))=200 GeV.

We report the measurement of direct photons at midrapidity in Au+Au collisions at √(s(NN))=200 GeV. The direct photon signal was extracted for the transverse momentum range of 4 GeV/c

Cold nuclear matter effects on J/ψ yields as a function of rapidity and nuclear geometry in d+A collisions at sqrt[s(NN)]=200 GeV.

We present measurements of J/ψ yields in d+Au collisions at sqrt[s(NN)]=200 GeV recorded by the PHENIX experiment and compare them with yields in p+p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/ψ rapidity (-2.2

Transition in yield and azimuthal shape modification in dihadron correlations in relativistic heavy ion collisions.

Hard-scattered parton probes produced in collisions of large nuclei indicate large partonic energy loss, possibly with collective produced-medium response to the lost energy. We present measurements of π^{0} trigger particles at transverse momenta p{T}{t}=4-12 GeV/c and associated charged hadrons (p{T}{a}=0.5-7 GeV/c) vs relative azimuthal angle Δϕ in Au+Au and p+p collisions at sqrt[s{NN}]=200 GeV. The Au+Au distribution at low p{T}{a}, whose shape has been interpreted as a medium effect, is modified for p{T}{t}<7 GeV/c. At higher p{T}{t}, the data are consistent with unmodified or very weakly modified shapes, even for the lowest measured p{T}{a}, which quantitatively challenges some medium response models. The associated yield of hadrons opposing the trigger particle in Au+Au relative to p+p (I{AA}) is suppressed at high p{T} (I{AA}≈0.35-0.5), but less than for inclusive suppression (R{AA}≈0.2).

Enhanced production of direct photons in Au + Au collisions at square root(S(NN)) = 200 GeV and implications for the initial temperature.

The production of e+ e- pairs for m(e+ e-)<0.3 GeV/c2 and 1

Charged Kaon interferometric probes of space-time evolution in Au+Au collisions at sqrt[S(NN)]=200 GeV.

Bose-Einstein correlations of charged kaons are used to probe Au+Au collisions at sqrt[S(NN)]=200 GeV and are compared to charged pion probes, which have a larger hadronic scattering cross section. Three-dimensional Gaussian source radii are extracted, along with a one-dimensional kaon emission source function. The centrality dependences of the three Gaussian radii are well described by a single linear function of N(part)1/3 with a zero intercept. Imaging analysis shows a deviation from a Gaussian tail at r greater than or approximately equal to 10 fm, although the bulk emission at lower radius is well described by a Gaussian. The presence of a non-Gaussian tail in the kaon source reaffirms that the particle emission region in a heavy-ion collision is extended, and that similar measurements with pions are not solely due to the decay of long-lived resonances.

Search for muon-neutrino to electron-neutrino transitions in MINOS.

This Letter reports on a search for nu(mu) --> nu(e) transitions by the MINOS experiment based on a 3.14x10(20) protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27+/-5(stat)+/-2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of nu(mu) --> nu(e) oscillations, this 1.5sigma excess of events is consistent with sin2(2theta(13)) comparable to the CHOOZ limit when |Delta m2|=2.43x10(-3) eV2 and sin2(2theta(23))=1.0 are assumed.

Elliptic flow for phi mesons and (anti)deuterons in Au+Au collisions at square root of sNN=200 GeV.

Differential elliptic flow (v(2)) for phi mesons and (anti)deuterons (d)d is measured for Au+Au collisions at square root of sNN=200 GeV. The v(2) for phi mesons follows the trend of lighter pi+/- and K+/- mesons, suggesting that ordinary hadrons interacting with standard hadronic cross sections are not the primary driver for elliptic flow development. The v(2) values for (d)d suggest that elliptic flow is additive for composite particles. This further validation of the universal scaling of v(2) per constituent quark for baryons and mesons suggests that partonic collectivity dominates the transverse expansion dynamics.

Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis.

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods. RESULTS: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.

Sulfonylurea receptor 1 and Kir6.2 expression in the novel human insulin-secreting cell line NES2Y.

NES2Y is a proliferating human insulin-secreting cell line that we have derived from a patient with persistent hyperinsulinemic hypoglycemia of infancy. This disease is characterized by unregulated insulin release despite profound hypoglycemia. NES2Y cells, like beta-cells isolated from the patient of origin, lack functional ATP-sensitive potassium channels (KATP) and also carry a defect in the insulin gene-regulatory transcription factor PDX1. Here, we report that the NES2Y beta-cells that are transfected with the genes encoding the components of KATP channels in beta-cells, sulfonylurea receptor (SUR) 1 and Kir6.2, have operational KATP channels and show normal intracellular Ca2+ and secretory responses to glucose. However, these cells, designated NESK beta-cells, have impaired insulin gene transcription responses to glucose. NES2Y beta-cells that are transfected with either Kir6.2 or SUR1 alone do not express functional KATP channels and have impaired intracellular free Ca2+ concentration-signaling responses to depolarization-dependent beta-cell agonists. These findings document that in NES2Y beta-cells, coexpression of both subunits is critically required for fully operational KATP channels and KATP channel-dependent signaling events. This article further characterizes the properties of the novel human beta-cell line, NES2Y, and documents the usefulness of these cells in diabetes-related research.

Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways.

Hyperinsulinism of infancy (HI) is a congenital defect in the regulated release of insulin from pancreatic beta-cells. Here we describe stimulus-secretion coupling mechanisms in beta-cells and intact islets of Langerhans isolated from three patients with a novel SUR1 gene defect. 2154+3 A to G SUR1 (GenBank accession number L78207) is the first report of familial HI among nonconsanguineous Caucasians identified in the U.K. Using patch-clamp methodologies, we have shown that this mutation is associated with both a decrease in the number of operational ATP-sensitive K+ channels (KATP channels) in beta-cells and impaired ADP-dependent regulation. There were no apparent defects in the regulation of Ca2+- and voltage-gated K+ channels or delayed rectifier K+ channels. Intact HI beta-cells were spontaneously electrically active and generating Ca2+ action currents that were largely insensitive to diazoxide and somatostatin. As a consequence, when intact HI islets were challenged with glucose and tolbutamide, there was no rise in intracellular free calcium ion concentration ([Ca2+]i) over basal values. Capacitance measurements used to monitor exocytosis in control and HI beta-cells revealed that there were no defects in Ca2+-dependent exocytotic events. Finally, insulin release studies documented that whereas tolbutamide failed to cause insulin secretion as a consequence of impaired [Ca2+]i signaling, glucose readily promoted insulin release. Glucose was also found to augment the actions of protein kinase C- and protein kinase A-dependent agonists in the absence of extracellular Ca2+. These findings document the relationship between SUR1 gene defects and insulin secretion in vivo and in vitro and describe for the first time KATP channel-independent pathways of regulated insulin secretion in diseased human beta-cells.

Radiologic determination of the caudal border of the spinal field in cranial spinal irradiation.

PURPOSE: The purpose of this paper is to determine the inferior border of the caudal sac which dictates the placement of the lower border of the spinal field in Cranial Spinal Irradiation. METHODS AND MATERIALS: We have reviewed the pre-treatment craniospinal Magnetic Resonance Imaging studies of 24 evaluable children with seeding central nervous system tumors who were treated at our institution with Cranial Spinal Irradiation since 1988. RESULTS: The Magnetic Resonance Imaging studies demonstrated significant variation in the terminal location of the caudal sac, ranging from S2 to S4. The most frequent termination was at S2 (12/24). In four patients (4/24), termination was at mid S1 and in eight others (8/24), it was found to be at or below S3. In addition, the presence of spinal metastases may displace the distal limit even further inferiorly. CONCLUSION: Rather than arbitrarily placing the inferior field edge at S2, we recommend individualizing the required margin for the spinal field which should be determined using sagittal T1-weighted images of the lumbosacral spine. This is particularly important in patients who present with spinal metastases, since tumor may extend the dural sac termination distally.

Childhood optic chiasm gliomas: radiographic response following radiotherapy and long-term clinical outcome.

PURPOSE: In children with chiasmal gliomas, radiation therapy can arrest progressive visual and neurologic impairment. We examined the radiographic response and clinical outcomes after irradiation. METHODS AND MATERIALS: Forty-two children (median age at diagnosis, 6.6 years) with chiasmal gliomas were managed as follows: 11 asymptomatic patients with neurofibromatosis-1 (NF-1) were observed only; 2 patients, less than 3 years old, underwent surgery and chemotherapy to delay irradiation; and 29 patients with progressive disease received radiation with or without prior surgery or chemotherapy. Time to radiographic response, long-term tumor control and late sequelae were reviewed for the 29 irradiated patients. RESULTS: The probability of at least 50% radiographic response at 24 months after irradiation was 18.1% and increased to 38.2% by 48 months and 45.9% by 60 months. By actuarial analysis, the median time for such radiographic response was 62 months. For the 29 irradiated patients, the 10-year freedom from progression and overall survival rates were 100% and 89%, respectively (median follow-up for surviving patients, 108 months). Stabilization or improvement in vision occurred in 81% of 26 evaluable irradiated patients. CONCLUSIONS: Notable radiographic response may be observed years after irradiation. Radiation therapy provides excellent long-term tumor control and vision preservation or improvement in the majority of patients with progressive chiasmal gliomas.

20-year experience in childhood craniopharyngioma.

PURPOSE: The management of craniopharyngioma is controversial, and surgery alone is frequently advocated. The purpose of this study was to assess the long-term impact of various treatments in childhood craniopharyngioma. METHODS AND MATERIALS: Sixty-one children < or = 21 years of age at diagnosis were treated for craniopharyngioma at Children's Hospital and the Joint Center for Radiation Therapy in Boston from 1970 to 1990. The median age was 7.5 years (range 10 months-21 years). There were 33 females and 28 males. The median follow-up was 10 years (range 2-20.5 years). Neuroimaging was available for detailed review in 53. Nine children were treated with radiotherapy alone, 15 were treated with surgery alone, and 37 were treated with both surgery and radiotherapy. All patients in the radiotherapy and surgery plus radiotherapy groups were treated with megavoltage radiation with a median dose of 5464 cGy. RESULTS: All nine of the children treated with radiation therapy alone are alive; none have recurred. Nine of the 15 children treated with surgery alone have recurred (p = 0.007 Fisher exact test). Two are alive with disease, and seven are alive without disease after treatment at relapse with radiation therapy, surgery, or both. Seven of the 37 patients treated with surgery plus radiotherapy have recurred. Three of the seven patients are dead of disease, three patients are alive with disease, and one patient is alive without disease after further treatment. The 10-year actuarial overall survival was 91% for all patients. The 10-year actuarial freedom from progression for the surgery group was 31% compared with 100% for patients treated with radiation therapy only (log rank p = 0.01), and 86% for patients treated with surgery plus radiotherapy at diagnosis (p = 0.001). There were two treatment related deaths, both in the surgery plus radiotherapy group. A higher incidence of visual loss and diabetes insipidus was associated with the use of aggressive surgery. The size of the tumor at presentation correlated with an increased risk of recurrence; 5 of 6 patients with tumors > or = 5 cm experienced recurrences while only 6 of 30 recurred when the tumor was < 5 cm. CONCLUSIONS: Overall survival in childhood craniopharyngioma is excellent. However, patients treated with surgery alone have a significantly worse freedom from progression when compared to patients treated with surgery and radiation therapy or radiation therapy alone.

Image fusion for stereotactic radiotherapy and radiosurgery treatment planning.

PURPOSE: We describe an image fusion application that addresses two basic problems that previously limited the use of magnetic resonance imaging (MRI) for geometric localization in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). The first limitation is imposed by the use of a relocatable, MRI-incompatible, stereotactic frame for stereotactic radiotherapy. The second limitation is an inherent lack of geometric fidelity in current MRI scanners that invalidates the use of MRI for stereotactic localization. METHODS AND MATERIALS: We recently developed and implemented a novel automated method for fusing computerized tomography (CT) and MRI volumetric image studies. The method is based on a chamfer matching algorithm, and provides a quality assurance procedure to verify the accuracy of the fused image set. The image fusion protocol removes the need for stereotactic fixation of the patient for the MRI study. RESULTS: The image fusion protocol significantly improves on the spatial accuracy of the MRI study. We demonstrate the effect of distortion and the effectiveness of the fusion with a phantom study. We present two case studies, an acoustic neurinoma treated with SRS, and a pilocytic astrocytoma treated with SRT. CONCLUSION: The image fusion protocol significantly improves our logistical management of treating patients with radiosurgery and makes conformal therapy practical for treating patients with SRT. The image fusion protocol demonstrates both the superior diagnostic quality and the poor geometric fidelity of MRI. MRI is a required imaging modality in stereotactic therapy. Image fusion combines the superior MRI diagnostic quality with the superior CT geometric definition, and makes the use of MRI in stereotactic therapy possible and practical.

Stereotactic radiotherapy for pediatric and adult brain tumors: preliminary report.

PURPOSE: Stereotactic radiotherapy is a new modality that combines the accurate focal dose delivery of stereotactic radiosurgery with the biological advantages of conventional radiotherapy (1.8-2.0 Gy/day using 25-30 fractions). The modality requires sophisticated treatment planning, dedicated high-energy linear accelerator, and relocatable immobilization devices. We report here our early experience using stereotactic radiotherapy for intracranial neoplasms. METHODS AND MATERIALS: Between June 1992 and September 1993, we treated 82 patients with central nervous system lesions using stereotactic radiotherapy, delivered from a dedicated 6 MV stereotactic linear accelerator. A head fixation frame provided daily relocatable setup using a dental plate for all patients over 8 years of age. A modified head frame, which does not require a mouthpiece, was used for children requiring anesthesia. The patients ranged in age from 9 months to 76 years. Thirty-three patients were children less than 21 years of age. Selection criteria for the protocol included: (a) focal, small (< 5 cm) radiographically distinct lesions known to be radiocurable (pituitary adenoma, craniopharyngioma, meningioma, acoustic neuroma, pilocytic astrocytoma, retinoblastoma), and (b) lesions located in regions not amenable to surgery or radiosurgery such as the brain stem or chiasm. Standard fractionation and conventional doses were delivered. Patients with low-grade astrocytoma, oligodendroglioma, or ependymoma were treated using a dose escalation regime consisting of conventional doses plus a 10% increase. RESULTS: Although follow-up is 16 months (range 3-16 months), posttreatment radiographic studies in 77 patients have been consistent with changes similar to those found after conventional radiation therapy. To date, reduction of up to 50% of the original volume has been noted in 19 out of 77 patients, and 4 patients had a complete response, 2 with dysgerminoma, and 1 each with astrocytoma and retinoblastoma. In 56 patients disease was either stable or the follow-up was too short for evaluation. While the follow-up is relatively short, there have been no in-field or marginal recurrences. The only unexpected radiographic findings were in three patients with pilocytic astrocytomas, who developed asymptomatic edema in the treatment volume. Accuracy in daily fractionation was excellent. In over 2000 patient setups with 41,000 scalp measurements, reproducibility was found to be within 0.41 mm (median) of baseline readings, allowing for precise immobilization throughout the treatment course. The treatment in all cases was well tolerated with minimal acute effects. Our stereotactic radiotherapy facility can provide fractionated therapy for 10-12 patients a day efficiently and accurately. CONCLUSIONS: The treatment and relocatable stereotactic head frames were well tolerated with minimal acute effects. No long-term sequelae have been noted, although the observation period is short. To fully define the role of stereotactic radiotherapy, we are conducting prospective studies to evaluate neurocognitive and neuroendocrine effects. We expect that this innovative approach will make a significant impact on the treatment of intracranial neoplasms, particularly in children.