Neutron Capture on the s-Process Branching Point

The neutron capture cross sections of several unstable nuclides acting as branching points in the s process are crucial for stellar nucleosynthesis studies. The unstable ^{171}Tm (t_{1/2}=1.92 yr) is part of the branching around mass A∼170 but its neutron capture cross section as a function of the neutron energy is not known to date. In this work, following the production for the first time of more than 5 mg of ^{171}Tm at the high-flux reactor Institut Laue-Langevin in France, a sample was produced at the Paul Scherrer Institute in Switzerland. Two complementary experiments were carried out at the neutron time-of-flight facility (n_TOF) at CERN in Switzerland and at the SARAF liquid lithium target facility at Soreq Nuclear Research Center in Israel by time of flight and activation, respectively. The result of the time-of-flight experiment consists of the first ever set of resonance parameters and the corresponding average resonance parameters, allowing us to make an estimation of the Maxwellian-averaged cross sections (MACS) by extrapolation. The activation measurement provides a direct and more precise measurement of the MACS at 30 keV: 384(40) mb, with which the estimation from the n_TOF data agree at the limit of 1 standard deviation. This value is 2.6 times lower than the JEFF-3.3 and ENDF/B-VIII evaluations, 25% lower than that of the Bao et al. compilation, and 1.6 times larger than the value recommended in the KADoNiS (v1) database, based on the only previous experiment. Our result affects the nucleosynthesis at the A∼170 branching, namely, the ^{171}Yb abundance increases in the material lost by asymptotic giant branch stars, providing a better match to the available pre-solar SiC grain measurements compared to the calculations based on the current JEFF-3.3 model-based evaluation.

Stellar

The ^{36}Ar(n,γ)^{37}Ar (t_{1/2}=35 d) and ^{38}Ar(n,γ)^{39}Ar (269 yr) reactions were studied for the first time with a quasi-Maxwellian (kT∼47 keV) neutron flux for Maxwellian average cross section (MACS) measurements at stellar energies. Gas samples were irradiated at the high-intensity Soreq applied research accelerator facility-liquid-lithium target neutron source and the ^{37}Ar/^{36}Ar and ^{39}Ar/^{38}Ar ratios in the activated samples were determined by accelerator mass spectrometry at the ATLAS facility (Argonne National Laboratory). The ^{37}Ar activity was also measured by low-level counting at the University of Bern. Experimental MACS of ^{36}Ar and ^{38}Ar, corrected to the standard 30 keV thermal energy, are 1.9(3) and 1.3(2) mb, respectively, differing from the theoretical and evaluated values published to date by up to an order of magnitude. The neutron-capture cross sections of ^{36,38}Ar are relevant to the stellar nucleosynthesis of light neutron-rich nuclides; the two experimental values are shown to affect the calculated mass fraction of nuclides in the region A=36-48 during the weak s process. The new production cross sections have implications also for the use of ^{37}Ar and ^{39}Ar as environmental tracers in the atmosphere and hydrosphere.

Evaluating the intensity of the 803-keV γ ray of 210Po using a 4παß(LS)-γ(HPGe) measurement system.

The absolute intensity for the 803-keV γ ray of 210Po was evaluated by α-γ coincidence technique. A liquid sample with a known amount of 210Po embedded in scintillation fluid was measured in a coincidence-based system that comprises a Liquid Scintillator (LS) detector and a High-Purity Germanium (HPGe) detector. A photo-reflector assembly that contains the 210Po sample provides 100% efficiency for detecting the α particles. The combination between the HPGe and the LS detectors allows to reject non-coincident α-γ events while maintaining high resolution γ spectroscopy. Consequently, the faint 803-keV photopeak from 210Po could be observed in a background-free environment, and its intensity could be evaluated with good accuracy. Sample measurements were carried out over nine months to gather statistics and verify the reliability of the experimental procedure. The absolute intensity of the 803-keV line was found to be (1.22 ± 0.03) × 10-5, in excellent agreement with the adopted value in a recent data compilation and consistent with previous experimental works.

High power high voltage bias-T for half wave resonators and radio frequency quadrupole couplers.

High power high voltage bias-T units capable of delivering up to 100 kW CW RF power at 176 MHz and up to 4 kV DC were developed at the Soreq Nuclear Research Center for the Soreq Applied Research Accelerator Facility linac. Two separate bias-T units with different requirements were designed for the radio frequency quadrupole couplers and the half wave resonator couplers. The purpose of this bias-T is to prevent multipacting phenomena by application of a high voltage DC bias to inner conductors of RF couplers. Underlying design principles, indigenous development, and successful off-line and on-line tests results are presented.

Evaluating the intensity of the 'prompt' 140.5 keV γ-ray of 99Mo using a 4παß(LS)-γ(HPGe) measurement system.

The absolute intensity for the 'prompt' 140.5 keV gamma-ray of 99Mo was evaluated using the ß-γ coincidence technique. A liquid sample of 99Mo was prepared from a99Mo/99mTc generator and measured in a 4παß(LS)-γ(HPGe) system that comprises a Liquid Scintillator (LS) detector and a High-Purity Germanium (HPGe) detector. The sample was introduced into scintillation fluid embedded in a photo-reflector assembly that provides almost 100% efficiency for detecting ß particles (in the energy range of intreset). The combination of the HPGe and the LS detectors provided a highly effective rejection mechanism for non-coincident events. Thereby, the distinction between the detected 140.5 keV events originating from decays of 99mTc (IT) and those from transitions bypassing the metastable state could be obtained and the 'prompt' intensity was evaluated directly. The system was calibrated for detecting ß particles and γ-rays using radioactive sources of known activities and having identical geometry as the sample containing 99Mo. The absolute intensity of the 'prompt' 140.5 keV was found to be (5.21 ± 0.02stat±0.16sys)%, in good agreement with results from more recently reported works.

A triplet of differently shaped spin-zero states in the atomic nucleus 186Pb

Understanding the fundamental excitations of many-fermion systems is of significant current interest. In atomic nuclei with even numbers of neutrons and protons, the low-lying excitation spectrum is generally formed by nucleon pair breaking and nuclear vibrations or rotations. However, for certain numbers of protons and neutrons, a subtle rearrangement of only a few nucleons among the orbitals at the Fermi surface can result in a different elementary mode: a macroscopic shape change. The first experimental evidence for this phenomenon came from the observation of shape coexistence in 16O (ref. 4). Other unexpected examples came with the discovery of fission isomers and super-deformed nuclei. Here we find experimentally that the lowest three states in the energy spectrum of the neutron deficient nucleus 186Pb are spherical, oblate and prolate. The states are populated by the alpha-decay of a parent nucleus; to identify them, we combine knowledge of the particular features of this decay with sensitive measurement techniques (a highly efficient velocity filters with strong background reduction, and an extremely selective recoil-alpha-electron coincidence tagging methods). The existence of this apparently unique shape triplet is permitted only by the specific conditions that are met around this particular nucleus.

An expanded Transactional Stress and Coping Model for siblings of children with sickle cell disease: family functioning and sibling coping, self-efficacy and perceived social support.

AIM: To investigate the application of an expanded Transactional Stress and Coping Model for the psychological adjustment of non-chronically ill, African-American siblings of children with sickle cell disease (SCD). METHODS: Ninety-seven siblings (M = 11.24 years) from 65 families who care for a child with SCD participated. Primary caregivers completed the Coping Health Inventory for Parents, the Family Relations Scale and the Child Behaviour Checklist, while siblings completed the Kidcope, the Children's Self-Efficacy for Peer Interaction Scale, and the Social Support Scale for Children. RESULTS: Family processes were predictive of sibling adjustment, revealing that family coping, expressiveness and support improved adjustment, while family conflict predicted poor adjustment. CONCLUSION: Findings suggest that family-centered interventions stressing family expressiveness and support, while minimizing conflict, will contribute to sibling psychological adjustment.

DNA repair, mitochondria, and neurodegeneration.

Accumulation of nuclear and mitochondrial DNA damage is thought to be particularly deleterious in post-mitotic cells, which cannot be replaced through cell division. Recent experimental evidence demonstrates the importance of DNA damage responses for neuronal survival. Here, we summarize current literature on DNA damage responses in the mammalian CNS in aging and neurodegeneration. Base excision repair (BER) is the main pathway for the removal of small DNA base modifications, such as alkylation, deamination and oxidation, which are generated as by-products of normal metabolism and accumulate with age in various experimental models. Using neuronal cell cultures, human brain tissue and animal models, we and others have shown an active BER pathway functioning in the brain, both in the mitochondrial and nuclear compartments. Mitochondrial DNA repair may play a more essential role in neuronal cells because these cells depend largely on intact mitochondrial function for energy metabolism. We have characterized several BER enzymes in mammalian mitochondria and have shown that BER activities change with age in mitochondria from different brain regions. Together, the results reviewed here advocate that mitochondrial DNA damage response plays an important role in aging and in the pathogenesis of neurodegenerative diseases.

Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study.

PURPOSE: Folic acid antagonists are reported to have activity against mesothelioma. The Cancer and Leukemia Group B (CALGB) undertook this phase II study of the new antifolate, trimetrexate (TMTX), to evaluate its response rate and toxicity in chemotherapy-naive patients with malignant mesothelioma. PATIENTS AND METHODS: Fifty-two patients were accrued to this protocol. Because of concerns about TMTX toxicity in patients with malignant effusions and/or hypoalbuminemia, the first 17 patients were treated at a dose of 6 mg/m2 daily for 5 days every 21 days. Because minimal toxicity was observed, the subsequent 35 patients were treated at a dose of 10 mg/m2. RESULTS: Two of 17 patients (12%) in the 6-mg/m2 treatment group had a partial response (PR) and four of 34 eligible patients (12%) in the 10-mg/m2 treatment group had a PR or regression (R) of assessable disease. No patient achieved a complete response (CR). Median survival durations were 5.0 and 8.9 months in the 6- and 10-mg/m2 treatment groups, respectively, while the 2-year survival rates were identical at 18%. At the 10-mg/m2 dose, toxicity was tolerable, with one toxic death from sepsis and a 12% rate of grade 4 thrombocytopenia and granulocytopenia. CONCLUSION: In this large trial, TMTX showed minor activity in the treatment of malignant mesothelioma. Myelosuppression was mild and dose-related. Future studies of higher doses of TMTX should be considered.

A phase I study of high-dose ifosfamide and escalating doses of carboplatin with autologous bone marrow support.

The dose-limiting toxicity in two separate phase I trials of the high-dose single agents ifosfamide and carboplatin was renal insufficiency at 18 g/m2 and hepatic and ototoxicity at 2,400 mg/m2, respectively. In this phase I study, 16 adults were treated with ifosfamide at 75% of the single-agent maximum-tolerated dose (MTD) (12 g/m2) and escalating doses of carboplatin (400 to 1,600 mg/m2) to determine the nonhematologic dose-limiting toxicity and the maximum-tolerated dose of the combination. Both drugs as well as mesna for uroprotection were given by continuous infusion over 4 days with an additional day of mesna (total dose per course, 15 g/m2). Autologous bone marrow support was stipulated for subsequent dose levels once granulocytes remained less than 500/microL for more than 14 days in two of three to five patients entered at a given dose level. Autologous bone marrow support was used at doses above the 400 mg/m2 carboplatin dose level. At the maximum-tolerated dose level of 1,600 mg/m2 of carboplatin, renal toxicity precluded further dose escalation. Of the five patients entered at this dose level, reversible creatinine elevation greater than 2 mg/dL (median peak, 2.6 mg/dL) was observed in three patients, and irreversible renal failure occurred in an additional patient (peak creatinine, 6.9 mg/dL. Transient gross hematuria appeared more common with the combination than with ifosfamide alone. Two patients developed severe somnolence and confusion associated with a rising creatinine. There were two complete (CRs) and four partial responses (PRs) in 14 heavily pretreated assessable patients (including four partial or complete responses in eight assessable patients with advanced refractory sarcoma, and one CR in two patients with germ cell carcinoma). Carboplatin and ifosfamide appear to have overlapping renal toxicity. Nevertheless, carboplatin and ifosfamide can be combined at 80% and 75% of the single-agent maximum-tolerated doses, respectively, with acceptable nonhematologic toxicity. Ifosfamide and carboplatin are an attractive core combination for further studies in the treatment of sarcoma, germ cell, ovarian, and lung carcinomas.

Demonstration of a high-intensity neutron source based on a liquid-lithium target for Accelerator based Boron Neutron Capture Therapy.

A free surface liquid-lithium jet target is operating routinely at Soreq Applied Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA continuous-wave narrow proton beam. The experiments demonstrate the liquid lithium target (LiLiT) capability to constitute an intense source of epithermal neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3)) for long periods of time, while maintaining stable conditions and localized residual activity. LiLiT generates ~3×10(10) n/s, which is more than one order of magnitude larger than conventional (7)Li(p,n)-based near threshold neutron sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT-doses produced in a phantom. According to these simulations it was found that a ~15 mA near threshold proton current will apply the therapeutic doses in ~1h treatment duration. According to our present results, such high current beams can be dissipated in a liquid-lithium target, hence the target design is readily applicable for accelerator-based BNCT.

Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy.

We designed a study to obtain follow-up on behavioral aspects of compliance with home deferoxamine administration, explore social factors that might influence compliance, and evaluate the effectiveness of a pilot intervention program for patients with thalassemia or sickle cell disease who were receiving chronic transfusion therapy. Thirty-one patients between the ages of 6 and 21 years and their primary caregivers were administered a 24-hour recall Interview about home care. Fifteen went on to participate in a Desferal Day Camp, which combined educational strategies with peer support. Behavioral measures of treatment adherence were similar for most patients with sickle cell disease and thalassemia. Patient compliance with days of deferoxamine administration at follow-up was associated with initial compliance, perceived support, and patient and caregiver knowledge. Increased sharing of responsibilities for home care by patients and caregivers and caregiver knowledge were associated with lower ferritin and liver iron levels. A subsample of 3 patients who were extremely noncompliant with days of deferoxamine administration was examined separately; these patients were found to be moderately compliant with the number of hours and amount of deferoxamine administered and to share fewer home care tasks with primary caregivers. Participation in Desferal Day Camp did not result in increases in knowledge or peer support, suggesting that future interventions should focus on family support and on improving self-regulatory skills. The crucial role of collaboration among patients, families, and health care providers in developing interventions to enhance adherence was emphasized.

High-dose thiotepa alone and in combination regimens with bone marrow support.

Curative treatment regimens for leukemias, lymphomas, and testicular cancer have been based on laboratory observations of a clear relationship (generally linear-log) between increasing doses of chemotherapeutic agents and tumor cytotoxicity and on recognition of the need for combination chemotherapy to avoid the emergence of drug resistance. Chemotherapeutic agents have been selected for combinations based on cytotoxic activity, different mechanisms of action (to avoid cross-resistance), and different dose-limiting toxicities (to avoid additive toxicity). The ideal combinations use the highest tolerable doses of active non-cross-resistant agents to minimize the potential for drug resistance and achieve optimum cytotoxicity. Dose escalation is often limited by myelosuppression. Hematologic stem cell support from bone marrow or peripheral blood allows the administration of significantly higher doses of chemotherapy. In 1977, Thomas and colleagues in Seattle reported that 13 of 100 patients who underwent bone marrow transplantation for relapsed acute leukemia were disease-free 1 to 4.5 years later. Today, almost 50% of selected patients with acute myelogenous leukemia who undergo transplantation with human leukocyte antigen-matched sibling donor marrow during first remission are cured. Between 20% and 50% of lymphoma patients who undergo transplantation after failing conventional treatment have survived; those whose disease is responding to standard-dose therapy at the time of transplant have the best prognosis. Conditioning regimens that are sufficiently cytoreductive are not currently available for patients with solid tumors. The diversity of solid tumors makes it likely that a variety of regimens will be required. In a sequence of laboratory and clinical studies, we have constructed and evaluated a regimen comprising 6 g/m2 of cyclophosphamide, 500 mg/m2 of N,N',N''-triethylenethiophosphoramide (thiotepa), and 800 mg/m2 of carboplatin. The response rate in women with measurable breast cancer was 81%. While profound myelosuppression was noted, organ toxicity has been rare. This regimen, designed to exploit the principles of curative cancer chemotherapy, is associated with low morbidity and high cytoreductive efficacy. The regimen is currently being evaluated in a phase II trial in patients with previously untreated metastatic breast cancer who are responsive to conventional-dose chemotherapy. Of 29 patients entered in the study, only one has died of toxicity, confirming the low incidence of treatment-related toxicity associated with the regimen.

Incidence of sudden infant death syndrome in Olmsted County, Minnesota: 1945 through 1992.

OBJECTIVE: To apply uniform diagnostic criteria for sudden infant death syndrome (SIDS) for an extended period for comparison of incidence rates from 1945 to 1992 in Olmsted County, Minnesota, to investigate the influence of a person-time or live birth denominator on the estimate of incidence, to calculate the proportionate mortality rate for SIDS over time, and to evaluate the accuracy of death certificates for case ascertainment and the role of interobserver variation in case classification. DESIGN: We retrospectively reviewed the autopsy results and complete medical records for all infant death from 1945 through 1992 for residents of Olmsted County, Minnesota. MATERIAL AND METHODS: Cases were identified from a computerized list of all Olmsted County deaths of infants occurring at ages 48 hours to 365 days. All resident cases were categorized as non-SIDS, possible SIDS, SIDS, or incomplete, on the basis of findings from autopsy and clinical history. Incidence rates were calculated for two different SIDS groups and with use of denominators of person-time and live births. RESULTS: For the study period, 82 cases of SIDS were identified (97% white and 3% Asian). The mean age at death was 12.5 weeks; male infants constituted 59% of cases. No significant trend in seasonal distribution was noted; 73% of deaths occurred between midnight and noon. The incidence rate, defined as SIDS definite and possible deaths per 1,000 resident live births, increased from 0.55 in 1950 through 1953 to 1.28 in 1990 through 1992. The secular trend was best described by a linear model with constant positive slope. Similar trends were observed with other definitions of incidence. During the study period, SIDS as a percentage of total infant deaths dramatically increased, ranging from 2.5 in 1950 through 1953 to 17.9 in 1990 through 1992. The death certificate diagnosis correctly predicted 72% of SIDS cases before 1970 and 100% of cases after 1970. CONCLUSION: Since 1945, the incidence of SIDS apparently has increased, although diagnostic transfer from other causes of death probably contributes to the observed trend. The comparison of live births versus person-time as denominators showed no significant difference in incidence rates. Interobserver reliability is modest for SIDS cases diagnosed before 1970 and may contribute to the variability in reported SIDS incidence rates.

Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma.

Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach.

Resource utilization associated with initial hospital stays complicated by early onset group B streptococcal disease.

BACKGROUND: The epidemiology of early onset neonatal group B streptococcal (GBS) disease has changed appreciably, but there are no recent assessments of the in-hospital resource utilization it incurs. STUDY DESIGN: We performed a retrospective cohort study of infants delivered from 1987 through 1995 at Massachusetts' largest obstetrics hospital. A matched cohort design was used to assess care occurring after transfer to another acute care hospital. RESULTS: There were 135 cases of early onset neonatal GBS infection complicating 85,062 deliveries (1.6/1,000 births) in 9 years, with a substantial decline beginning in 1994, when maternal intrapartum chemoprophylaxis was widely introduced. Most (73%) infants had birth weights of 2500 g or more; 93% survived. Overall both the median and mean lengths of stay were 8 days longer for infants with GBS disease than for those without this infection (P < 0.001). Total hospital charges for neonates with GBS disease also were higher, with the difference in medians of $5323 and in means of $10,004 (P < 0.001). Differences were greatest among >2500-g birth weight infants; no excess was evident for infants with birth weights of < 1500 g. CONCLUSION: There was a substantial excess length of stay and charges associated with early onset neonatal GBS disease, although this was less than previously reported.

Escalating doses of carboplatin with high-dose ifosfamide using autologous bone marrow as support: a phase I study.

In this phase I study, 16 adult cancer patients were treated with concurrent 4-day continuous infusions of ifosfamide at 12 g/m2 and escalating doses of carboplatin (400-1600 mg/m2) to determine the major non-haematological dose-limiting toxicity of the combination. Mesna was given by continuous infusion over 5 days for uroprotection (total dose per course = 15 g/m2). Autologous bone marrow support, which was mandated for subsequent dose levels once granulocytes remained below 500/microliters for more than 14 days in at least 2 patients entered at a given dose level, was used at dose levels above 400 mg/m2 carboplatin. Renal toxicity became dose-limiting at the maximum tolerated dose level of 1600 mg/m2 carboplatin. Temporary creatinine elevations above 2 mg/dl (median peak 2.6 mg/dl) were observed in 3 and irreversible renal toxicity occurred in 1 (peak creatinine 6.9 mg/dl, chronic creatinine 5-6 mg/dl) of the 5 patients entered at this dose level. Severe confusion and lethargy associated with rising creatinine developed in 2 patients. Two complete and four partial responses were documented in 14 heavily pretreated evaluable patients. The complete responses continue at 14+ and 20+ months in a patient with germ cell carcinoma and Ewing's sarcoma, respectively. Carboplatin appears to contribute to the renal toxicity of ifosfamide. Nevertheless, the combination of carboplatin and ifosfamide at 80% and 75% of the single-agent maximal tolerated doses respectively produced acceptable non-haematological toxicity. Further studies in the treatment of sarcoma, germ cell, ovarian and lung carcinomas with this combination are warranted.

Multiple-dose phase I trials--normal volunteers or patients? One viewpoint.

Traditionally, Phase I tolerance trials have been done with normal volunteers to establish single- and multiple-dose tolerance. We feel that the justification for doing multiple-dose tolerance studies in normals is open to question and that, in fact, more pertinent data can be generated by using the appropriate patient populations for these studies.

Effect of flurazepam on common clinical laboratory tests.

Twenty-two clinical laboratory tests performed on blood samples from 16 normal subjects following one week of either flurazepam or placebo administered in a double-blind method showed no apparent chemical interference by flurazepam on any of the testing procedures.

Keratinizing dermatoses. Combined data from four centers on short-term topical treatment with tretinoin.

In four medical centers, 40 patients with keratinizing dermatoses were treated with topical tretinoin (vitamin A acid) 0.1% cream and salicylic acid 2% cream in a short-term, double-blind study. Tretinoin was the more effective treatment for several of the keratinizing dermatoses with the exception of palmar-plantar hyperkeratosis, for which it was not effective in the concentration and method of application used. The most striking clinical responses occurred in patients with lamellar ichthyosis and ichthyosis vulgaris. Local adverse reactions-chiefly pruritus, erythema, burning, excoriation, and irritation-were not severe and could be controlled by modification of the treatment regimen.