Intrinsic thermalization of the honeycomb optical lattice.

Ultracold atoms confined to optical lattices provide a platform for simulation of phenomena not readily accessible in condensed matter and chemical systems. One area of growing interest is the mechanism by which isolated condensed matter systems can thermalize. The mechanism for thermalization of quantum systems has been directly linked to a transition to chaos in their classical counterpart. Here we show that the broken spatial symmetries of the honeycomb optical lattice leads to a transition to chaos in the single-particle dynamics which, in turn, causes mixing of the energy bands of the quantum honeycomb lattice. For systems with single-particle chaos, "soft" interactions between atoms can cause the system to thermalize (achieve a Fermi-Dirac distribution for fermions or a Bose-Einstein distribution for bosons).

Monte Carlo simulations and experimental results on neutron production in the uranium spallation target QUINTA irradiated with 660 MeV protons.

The activation experiment was performed using the accelerated beam of Phasotron accelerator at the Joint Institute for Nuclear Research (JINR). The natural uranium spallation target QUINTA was irradiated with protons with energy 660 MeV. Monte Carlo simulations of neutron production were performed using the Geant4 code. The number of leakage neutrons from the sections of the uranium target surrounded by the lead shielding and the number of leakage neutrons from lead were determined. The total number of fissions in the setup QUINTA was determined. Experimental values of reaction rates for the produced nuclei in the 127I sample were obtained and several values of reaction rates were compared with the results of simulations. Experimentally determined fluence of neutrons in energy interval 10-175 MeV using the (n,xn) reactions in the 127I(NaI) sample was compared with the results of simulations. Possibility of transmutation of the long-lived radionuclide 129I in the QUINTA setup was estimated.

Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors.

PURPOSE: This phase I study endeavored to estimate the maximum tolerated dose and describe the dose-limiting toxicities (DLTs) of oral irinotecan with gefitinib in children with refractory solid tumors. METHODS: Oral irinotecan was administered on days 1-5 and 8-12 with oral gefitinib (fixed dose, 150 mg/m(2)/day) on days 1-12 of a 21-day course. The escalation with overdose control method guided irinotecan dose escalation (7 dose levels, range 5-40 mg/m(2)/day). RESULTS: Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in ten patients. Diagnoses included osteosarcoma (N = 5), neuroblastoma (N = 3), sarcoma (N = 3), and others (N = 5). Patients received a median of two courses (range 1-20), with at least two patients treated on dose levels 2-7. Three patients had five DLTs; the most common being metabolic (hypokalemia, N = 2 and hypophosphatemia, N = 1) at dose levels two (10 mg/m(2)) and four (20 mg/m(2)). One patient experienced grade 3 diarrhea (40 mg/m(2)). Irinotecan bioavailability was 2.5-fold higher when co-administered with gefitinib, while the conversion rate of irinotecan to SN-38 lactone was unaffected. The study closed due to poor accrual before evaluation of the next recommended irinotecan dose level (35 mg/m(2)). Of 11 patients receiving at least two courses of therapy, three had stable disease lasting two to four courses and one patient maintained a complete response through 18 courses. CONCLUSIONS: The combination of oral gefitinib and irinotecan has acceptable toxicity and anti-tumor activity in pediatric patients with refractory solid tumors. Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure.

Neutron cross-sections for next generation reactors: new data from n_TOF.

In 2002, an innovative neutron time-of-flight facility started operation at CERN: n_TOF. The main characteristics that make the new facility unique are the high instantaneous neutron flux, high resolution and wide energy range. Combined with state-of-the-art detectors and data acquisition system, these features have allowed to collect high accuracy neutron cross-section data on a variety of isotopes, many of which radioactive, of interest for Nuclear Astrophysics and for applications to advanced reactor technologies. A review of the most important results on capture and fission reactions obtained so far at n_TOF is presented, together with plans for new measurements related to nuclear industry.

Direct nn-Scattering Measurement With the Pulsed Reactor YAGUAR.

Although crucial for resolving the issue of charge symmetry in the nuclear force, direct measurement of nn-scattering by colliding free neutrons has never been performed. At present the Russian pulsed reactor YAGUAR is the best neutron source for performing such a measurement. It has a through channel where the neutron moderator is installed. The neutrons are counted by a neutron detector located 12 m from the reactor. In preliminary experiments an instantaneous value of 1.1 × 10(18)/cm(2)s was obtained for the thermal neutron flux density. The experiment will be performed by the DIANNA Collaboration as International Science & Technology Center (ISTC) project No. 2286.

Neutron capture cross section measurement of 151Sm at the CERN neutron time of flight facility (n_TOF).

The151Sm(n,gamma)152Sm cross section has been measured at the spallation neutron facility n_TOF at CERN in the energy range from 1 eV to 1 MeV. The new facility combines excellent resolution in neutron time-of-flight, low repetition rates, and an unsurpassed instantaneous luminosity, resulting in rather favorable signal/background ratios. The 151Sm cross section is of importance for characterizing neutron capture nucleosynthesis in asymptotic giant branch stars. At a thermal energy of kT=30 keV the Maxwellian averaged cross section of this unstable isotope (t(1/2)=93 yr) was determined to be 3100+/-160 mb, significantly larger than theoretical predictions.

Sonographic appearance of appendicitis in a neutropenic pediatric patient after inversion appendectomy.

The technique of inversion-ligation appendectomy is used by some surgeons to eliminate the risk of peritoneal contamination as the result of incidental appendectomy during an otherwise clean surgical procedure. In most cases, the intussuscepted appendix necroses and sloughs into the cecum after several days. We present the first report of the ultrasonographic appearance of a retained, inflamed appendix, which occurred in a neutropenic pediatric patient 15 months after inversion appendectomy. Our case illustrates the importance of a complete surgical history for the interpretation of abnormal sonographic findings of the cecum.

End-of-life decision making by adolescents, parents, and healthcare providers in pediatric oncology: research to evidence-based practice guidelines.

Participating in end-of-life decisions is life altering for adolescents with incurable cancer, their families, and their healthcare providers. However, no empirically developed and validated guidelines to assist patients, parents, and healthcare providers in making these decisions exist. The purpose of the work reported here was to use three sources (the findings of three studies on decision making in pediatric oncology, published literature, and recommendations from professional associations) to develop guidelines for end-of-life decision making in pediatric oncology. The study designs include a retrospective, descriptive design (Study 1); a prospective, descriptive design (Study 2); and a cross-sectional, descriptive design (Study 3). Settings for the pediatric oncology studies included a pediatric catastrophic illness research hospital located in the Midsouth (Studies 1 and 2); and that setting plus a children's hospital in Australia and one in Hong Kong (Study 3). Study samples included 39 guardians and 21 healthcare providers (Study 1); 52 parents, 10 adolescents, and 22 physicians (Study 2); and 43 parents (Study 3). All participants in the studies responded to six open-ended questions. A semantic content analysis technique was used to analyze all interview data. Four nurses independently coded each interview; interrater reliability per code ranged from 68% to 100% across studies. The most frequently reported influencing factors were "information on the health and disease status of the patient," "all curative options having been attempted," "trusting the healthcare team," and "feeling support from the healthcare provider." The agreement across studies regarding influencing factors provides the basis for the research-based guidelines for end-of-life decision making in pediatric oncology. The guidelines offer assistance with end-of-life decision making in a structured manner that can be formally evaluated and individualized to meet patient and family needs.

Haemopoietic growth factors in paediatric oncology: a review of the literature.

Recombinant haemopoietic growth factors (HGFs) are an attractive adjunct to reduce morbidity from chemotherapy regimens and their use has become widespread in paediatric oncology. Although patients receiving HGFs often have faster haematological recovery after intensive chemotherapy, this does not always translate into meaningful clinical benefits. This article reviews the clinical effectiveness of HGFs in a variety of different contexts. Most published studies have used granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as prophylaxis to ameliorate the subsequent neutropenia following intensive chemotherapy. These 2 agents have also been used to mobilise peripheral blood stem cells for autologous transplantation. HGFs specific for anaemia and thrombocytopenia are currently in paediatric clinical trials and it is hoped that the proper context and administration strategy can be found to make their use clinically effective. This article also reviews data on toxicity, specifically focusing on differences between various formulations of growth factors. HGFs are expensive, and cost-benefit analyses reviewed in this article give an important perspective on the financial aspects of paediatric cancer care. Because HGFs do not benefit every child receiving chemotherapy and overuse increases costs and may result in unnecessary adverse effects, evidence-based guidelines for their rational use in paediatric oncology are proposed.

The role of peers in the emergence of heterosexual romantic relationships in adolescence.

Adolescents' peer structures and the quality of their friendships were explored as antecedents of romantic relationships. Longitudinal data were gathered in a sample of 180 high school students over a 3-year period from grade 9 to grade 11. Consistent with Dunphy (1963), small groups of close friends were predictive of other-sex peer networks which were, in turn predictive of the emergence of future romantic relationships. Indirect effects were found for same-sex groups of close friends and same-sex networks. Consistent with Furman and Wehner (1994), the qualitative features of relationships with both friends and romantic partners were predictive of the qualitative features of subsequent romantic experiences. These linkages suggest ways in which peer relationships may support romantic development at this stage of the life cycle.

An international feasibility study of parental decision making in pediatric oncology.

PURPOSE/OBJECTIVES: To describe parental decision making about treatment options for children with cancer and determine the feasibility of a similar but larger international study. DESIGN: Exploratory. SETTINGS: A pediatric catastrophic illness research hospital in the United States and children's hospitals in Australia and Hong Kong. SAMPLE: A convenience sample of 43 parents (5 fathers and 38 mothers ages 23-59 years). METHODS: Six open-ended interview questions posed to parents during private individual interviews. Content analysis techniques were used. MAIN RESEARCH VARIABLES: Parental perceptions of (a) factors considered in the decision-making process, (b) behaviors of healthcare professionals that affected the process, and (c) satisfaction with the process. Feasibility of a larger study was estimated by considering ease of access to parents, number of refusals to participate, understanding of the interview questions, and level of interest at each setting. FINDINGS: Access to parents was possible at all sites. Refusal to participate was reported only at the U.S. site. Certain factors (e.g., getting information from the healthcare team, trusting staff) were important to all parents considering end-of-life decisions. Site-specific factors included considering alternative therapies (at the Australian site) and strengthening faith (at the U.S. site). CONCLUSIONS: A larger international study of parental decision making is feasible. Sufficient similarities in parental decision making exist across these sites to justify future efforts to identify universal decision-making factors that, in conjunction with site-specific differences, could be helpful in developing guidelines for healthcare professionals who assist parents in making treatment-related decisions for a sick child.

Clinical use of topoisomerase I inhibitors in anticancer treatment.

The camptothecin analogs topotecan and irinotecan have shown to be among the most effective anticancer agents and, as S-phase specific agents, their antitumor effect is maximized when they are administered in protracted schedules. The documented activity as single agents in many adult and pediatric malignancies has been followed by their use in combination with other anticancer agents. These studies have shown promising results, and have placed topotecan and irinotecan in the first line treatment for some malignancies. However, studies to better determine the optimal schedules and sequence of combinations are needed.

Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies.

There is a paucity of radiologic literature addressing neurologic emergencies in children receiving therapy for non-CNS primary malignancies. In the acute setting, many of these children present to local community hospitals. This pictorial is from a single institutional experience describing the spectrum of neurologic emergencies seen in children with non-CNS cancers. We hope to familiarize pediatric radiologists with these entities in order to expedite diagnosis, facilitate treatment, and minimize morbidity and mortality that may be associated with these complications.

CNS involvement in children with newly diagnosed non-Hodgkin's lymphoma.

PURPOSE: To determine the frequency of CNS involvement at diagnosis of non-Hodgkin's lymphoma (NHL), to characterize its pattern of presentation, and to determine its prognostic significance. PATIENTS AND METHODS: We reviewed the records of 445 children (1975 through 1995) diagnosed with NHL (small noncleaved cell NHL/B-cell acute lymphoblastic leukemia [SNCC NHL/B-ALL], 201 patients; lymphoblastic, 113; large cell, 119; other, 12). Tumor burden was estimated by serum lactate dehydrogenase (LDH) measurement and reclassification of disease stage irrespective of CNS involvement (modified stage). RESULTS: Thirty-six of 445 children with newly diagnosed NHL had CNS involvement (lymphoma cells in the CSF [n = 23], cranial nerve palsy [n = 9], both features [n = 4]), representing 13%, 7%, and 1% of small noncleaved cell lymphoma, lymphoblastic lymphoma, and large-cell cases, respectively. By univariate analysis, CNS disease at diagnosis did not significantly impact event-free survival (P =. 095), whereas stage and LDH did; however, children with CNS disease at diagnosis were at 2.0 times greater risk of death than those without CNS disease at diagnosis. In a multivariate analysis, CNS disease was not significantly associated with either overall or event-free survival, whereas both serum LDH and stage influenced both overall and event-free survival. Among cases of SNCC NHL/B-ALL, CNS disease was significantly associated with event-free and overall survival (univariate analysis); however, in multivariate analysis, only LDH had independent prognostic significance. Elevated serum LDH or higher modified stage were associated with a trend toward poorer overall survival among children with CNS disease. CONCLUSION: A greater tumor burden at diagnosis adversely influences the treatment outcome of children with NHL and CNS disease at diagnosis, suggesting a need for ongoing improvement in both systemic and CNS-directed therapy.

Pharmacokinetics of irinotecan and its metabolites SN-38 and APC in children with recurrent solid tumors after protracted low-dose irinotecan.

Irinotecan (IRN), a topoisomerase I interactive agent, has significant antitumor activity in early Phase I studies in children with recurrent solid tumors. However, the disposition of IRN and its metabolites, SN-38 and APC, in children has not been reported. Children with solid tumors refractory to conventional therapy received IRN by a 1-h i.v. infusion at either 20, 24, or 29 mg/m2 daily for 5 consecutive days for 2 weeks. Serial blood samples were collected after doses 1 and 10 of the first course. IRN, SN-38, and APC lactone concentrations were determined by an isocratic high-performance liquid chromatography assay. A linear four-compartment model was fit simultaneously to the IRN, SN-38, and APC plasma concentration versus time data. Systemic clearance rate for IRN was 58.7 +/- 18.8 liters/h/m2 (mean +/- SD). The mean +/- SD ng/ml x h single-day lactone SN-38 area under the concentration-time curve (AUC(0-->6) was 90.9 +/- 96.4, 103.7 +/- 62.4, and 95.3 +/- 63.9 at IRN doses of 20, 24, and 29 mg/m2, respectively. The relative extent of IRN conversion to SN-38 and metabolism to APC measured after dose 1 were 0.49 +/- 0.33 and 0.29 +/- 0.17 (mean +/- SD). No statistically significant intrapatient difference was noted for SN-38 area under the concentration-time curve. Large interpatient variability in IRN and metabolite disposition was observed. The relative extent of conversion and the SN-38 systemic exposure achieved with this protracted schedule of administration were much greater than reported in adults or children receiving larger intermittent doses.

3D gadolinium-enhanced MRA: evaluation of hepatic vasculature in children with hepatoblastoma.

We used contrast-enhanced three-dimensional magnetic resonance angiography (3D MRA) modified for pediatric use to evaluate the hepatic vasculature prior to partial hepatectomy in five consecutive children with hepatoblastoma. Modifications included non-breath-hold technique in four of the five children who were sedated. The single breath-hold technique was performed in only one awake child. Scan delay times were based on contrast infusion time rather than total infusion time. The hepatic artery, portal vein, and inferior vena cava were identified in all patients. MRA findings were confirmed by conventional angiography in one patient and by surgery in all. Contrast-enhanced 3D MRA is a useful and rapid technique prior to partial hepatectomy in patients with hepatoblastoma.

Sexual victimization and perceptions of close relationships in adolescence.

An attachment perspective is proposed as a framework for conceptualizing the impact of sexual victimization on close relationships. Two studies were conducted to empirically examine the links between sexual victimization and perceptions of romantic, parental, and peer relationships. Study One included 154 undergraduate women, and Study Two included 48 high school seniors. In both studies, approximately half the women reported having experienced some form of coerced sexual experience. The majority were victimized by an acquaintance, and most victims had experienced multiple incidents. The first study found that victimized women had significantly more preoccupied romantic views than nonvictimized women. Retrospective reports indicated that women victimized in college were significantly more dismissing with their fathers in high school. In Study Two, victims reported more negative interactions with romantic partners, but no differences were found for romantic styles. Victims also reported more dismissing parental styles and more negative interactions with their fathers than nonvictims.

Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children.

PURPOSE: In a preclinical model of neuroblastoma, administration of irinotecan daily 5 days per week for 2 consecutive weeks ([qd x 5] x 2) resulted in greater antitumor activity than did a single 5-day course with the same total dose. We evaluated this protracted schedule in children. PATIENTS AND METHODS: Twenty-three children with refractory solid tumors were enrolled onto a phase I study. Cohorts received irinotecan by 1-hour intravenous infusion at 20, 24, or 29 mg/m(2) (qd x 5) x 2 every 21 days. RESULTS: The 23 children (median age, 14.1 years; median prior regimens, two) received 84 courses. Predominant diagnoses were neuroblastoma (n = 5), osteosarcoma (n = 5), and rhabdomyosarcoma (n = 4). The dose-limiting toxicity was grade 3/4 diarrhea and/or abdominal cramps in six of 12 patients treated at 24 mg/m(2), despite aggressive use of loperamide. The maximum-tolerated dose (MTD) on this schedule was 20 mg/m(2)/d. Five patients had partial responses and 16 had disease stabilization. On day 1, the median systemic exposure to SN-38 (the active metabolite of irinotecan) at the MTD was 106 ng-h/mL (range, 41 to 421 ng-h/mL). CONCLUSION: This protracted schedule is well tolerated in children. The absence of significant myelosuppression and encouraging clinical responses suggest compellingly that irinotecan be further evaluated in children using the (qd x 5) x 2 schedule, beginning at a dose of 20 mg/m(2). These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials.