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10503 Background: The IGF1 system has been implicated in sarcoma development and inhibition of IGF1R function has been shown to induce clinical responses in select sarcomas. Methods: Objectives included response rate (RR) and progression-free survival (PFS) to R1507 in patients with recurrent or refractory Ewing's (ES, 2 cohorts- primary refractory vs. others) osteo (OS), synovial (SS), rhabdomyosarcoma (RMS), and other sarcomas. Eligibility included recurrent/refractory measurable disease, age ≥ 12 yrs, life expectancy ≥ 6 weeks, Karnofsky PS ≥ 70, adequate renal, hepatic and bone marrow function. R1507 was administered i.v. at 9 mg/kg over one hour weekly. Response was assessed by WHO criteria every 6 wks X 4 and every 12 wks thereafter. A two-stage design (Green and Dahlberg) was used. The endpoint for the primary refractory ES cohort was PFS at week 18 (planned n=65). RR was the primary endpoint for the remaining cohorts (planned n=240). Results: From 12/07–12/08, 203 eligible patients from 29 centers across the US, Europe and Australia were enrolled. Age ranged from 12–85 yrs (median=27 yrs) and 126 were male. Verified histologic subtypes were ES (n=71), OS (n=43), RMS (n=28), SS (n=25), and others (n=25). 15 severe adverse events were reported in 9 patients, the most common being fatigue (n=2), thrombocytopenia (n=2), dehydration (n=2), and hyperglycemia (n=2). Clinically significant activity has been observed in ES, RMS and OS with several dramatic responses seen in ES and RMS. Independent radiologic review is currently ongoing and updated data will be presented. Conclusions: The rapid accrual amongst many centers in diverse geographical locations demonstrates the feasibility of collaborative research in sarcomas. R1507 is well tolerated and a promising new agent for the treatment of various sarcomas. SARC and Roche are collaborating in additional clinical trials to better define the role of R1507 in the treatment of selected sarcomas. [Table: see text]

The kinetics of the solvolysis of the ion trans-[Coen2N3Cl]+ have been investigated at several temperatures in mixtures of water with t-butyl alcohol with concentrations of the latter ranging up to 50 vol% or a mol fraction of 0.16. Values for the enthalpy and entropy of activation show sharp changes with changing solvent composition which can be correlated with extrema in the physical properties of the mixture concerned with sharp changes in solvent structure. Plots of log(rate constant) against the reciprocal of the dielectric constant and against the Grunwald-Winstein Y factor are both curved. The application of a free energy cycle shows that the effect of changes in solvent structure on the solvolysis dominates on the cobalt(III) cation in the transition state over that on the cation in the initial state.

Rate constants for the solvolysis of the complex ioncis-[Coen2N3Cl]+ have been determined for a range of temperatures in mixtures of water witht-butanol ranging up to 50% v/v of the latter. Linear plots of log (rate constant) against the reciprocal of the absolute temperature are obtained at all concentrations oft-butanol and the variations of the enthalpy and entropy of activation with solvent composition show extrema at compositions where extrema occur in the physical properties of the mixture which are influenced by solvent structure. The importance of solvent structure is shown by the curved plot found for log (rate constant) against reciprocal of dielectric constant at constant temperature. The application of a free energy cycle to the free energies of activation in water and in the mixture and the free energies of transfer of individual ionic species between water and the mixtures shows that the effect of changes in solvent structure on the reacting cation in the transition state dominates over that in the initial state.

The energy level schemes of192Os and192Pt have been established on the basis ofγ- γ coincidence studies using a dual parameter data collection system. Ge(Li) detectors were employed to study the gamma spectra produced in the E.C. andβ− decays of192Ir to192Os and192Pt, respectively. Thirteen new transitions and three new levels at 1,146.95, 1,237.35 and 1,913.76 keV are suggested. Relative intensities from singles measurements, branching ratios,α(K) and log ft values were calculated and multipolarities, spins and parities deduced. Comparisons are made with predictions of the Interacting Boson Model calculated on the basis of an O(6) to SU(3) transition.

A synopis of the transmutations of matter in a supernova to the final stages of neutron-star matter, r-nuclei, p-nuclei and cosmic rays if given. In particular discussed are (1) the freezing-out of nuclear reactions during cooling, (2) the consequences of an improved β-decay and β-delayed neutron emission systematics for the calculations of the r-process element abundances and of its application to the estimation of the nucleosynthesis-age of the galaxy, (3) the production mechanism of the high-energy light-element cosmic rays, which we propose to originate from the neutron star's surface.

Summary Head circumference was related to weight, chest circumference, supine length, and crown rump length at birth, 6 weeks, 3 months and 6 months in fifty boys and fifty-six girls. 1. The head circumference is highly correlated with body size especially at birth and 6 weeks. 2. The head circumference shows the best correlation with weight and chest circumference, particularly the weight, in both sexes.

ObjectiveEndoscopic vein harvest (EVH) has been demonstrated to improve early morbidity when compared with conventional open vein harvest (OVH) technique for infrainguinal bypass surgery. However, recent literature suggests conflicting results regarding mid- and long-term patency with EVH. The purpose of this study is to compare graft patency between harvest techniques specifically in patients with critical limb ischemia.MethodsThis retrospective study compared two groups of patients (EVH = 39 and OVH = 49) undergoing lower extremity revascularization from January 2009 to December 2011. Outcome measures included patency rates, postoperative complications, and wound infection. Graft patency was assessed using Kaplan-Meier curves.ResultsBoth groups were matched for demographics and indications for bypass (critical limb ischemia). Median follow-up was 22 months. There was a significant reduction in the incidence of wound infection at the vein harvest site in the EVH group (OVH = 20%; EVH = 0%; P < .001), nevertheless, the difference was not significant when only the anastomotic sites were included (OVH = 12.2%; EVH = 15.4%; P = .43). The hospital length of stay was comparable between the two groups (EVH = 8.73 ± 9.69; OVH = 6.35 ± 3.28; P = .26) with no significant difference in the recovery time. Primary graft patency rate was 43.2% in the EVH group and 69.4% in the OVH group (P = .007) at 3 years. The most common reason for loss of primary patency was graft occlusion (61.5%) in the OVH group and vein graft stenosis (54.5%) in the EVH group. The average number of vascular reinterventions per bypass graft was significantly lower in the OVH group compared with the EVH group (OVH = 0.37; EVH = 1.28; P < .001).ConclusionsOur findings demonstrate inferior primary patency when using the technique of EVH. Additionally, we identified a significantly higher rate of reintervention in the EVH cohort as well as a higher rate of vein graft body stenosis. However, EVH was associated with a decreased rate of wound complications with similar limb salvage and secondary patency rates when compared to OVH. EVH should therefore be selectively utilized in patients at high risk for wound complications.

3-Methyl or 3-phenyl-5-chloro-1-phenyl-4-phenylazopyrazole with primary amines, sodium polysulfide and sodium azide yielded amines, disulfides and 2,4-dihydropyrazolo[3,4-d]-1,2,3-triazoles respectively. 4-Amino-5-anilino-1,3-diphenylpyrazole was also prepared and characterized.

This study investigates the relation of malnutrition as indexed by hemoglobin levels and anthropometry and the fertility of Egyptian rural women. 357 married women in 2 villages in Beheira governorate, aged 15-45 were interviewed. 40.9% were in the optimum childbearing age (20-30 years); mean age was 30.5 years. Mean duration of married life was 10.96 years. The frequency distribution curve of hemoglobin of the group was shifted to the left, indicating a high prevalence of anemia. Mean body weight ranged between 62-64 kg, mean height between 158-63 cm, and mean body index between 2.31-2.85. Weight percentiles and degree of anemia shared a bimodal distribution, while the weight for height percentiles and degree of anemia showed a normal distribution with a shift to the left indicating prevalence of underweight for height. The group had an average of 3.6 previous pregnancies; the highest average was 6.7 attained at the age of 40-45 years. Mean pregnancy interval was 2.14 years; number of live births was an average of 3.27; abortion experiences on the average was 0.22; mean stillbirths was 0.07; highest average child losses was for ages 40-45, 0.75; average number of living children 2.8; and mean reproductive activity increased with increase in years of married life. Anemia tends to reduce fertility at all ages with the mean parity higher in the total normal group (3.44) than in the anemic (3.27). Mean family size was also higher in the normal (3.18) than anemic (2.7) groups. In anemic women percentages of live births was 97.7% compared with 94.4% in the normal group, pregnancy wastage was 10.1% compared to 4% in the normal group and total child losses was 11.3% compared to 10.8% in the normal group. The differences are not considered to be statistically significant. The data indicated that interaction between nutritional states, environmental conditions, and fertility performance is the major determinant of human reproduction.

Summary This was a follow-up study of physical growth of children who have had failure to thrive. It comprised 77 children in whom the cause was corrected and 35 children with persistent organic cause together with 10 children in whom the patent ductus arteriosus was ligated after the first year. The treated group consisted of surgical and medical cases. Their pattern of growth was compared with that of a control group composed of 75 children from the fracture clinic and 24 siblings, all from the same age range and nearly the same mean age. Seven parameters of growth were tested. Significant retardation in six parameters was noted in both the treated group (in which the cause of failure to thrive was removed) and the untreated group (in which the treatment of the cause was impossible). In the treated group, the mean skeletal age was less retarded than the mean height, while the mean head circumference of females was significantly more retarded than that of males. There was only slight difference between early and late ligation of patent ductus arteriosus in subsequent physical growth. Neither the very early onset of failure nor its severity caused a severe retardation within the treated group. Prolonged duration of failure to thrive or failure to correct the cause in the first year led to significant subsequent growth retardation within the treated group. Parental height and birth weight played a less well defined role, while socio-economic environment played a minor role in causing growth retardation in the treated group. The first year can only be regarded as a relatively critical period concerning subsequent physical growth due to difficulty in separating the effect of illness from that of genetic endowment. Growth retardation may represent another congenital abnormality independent of the original anomaly which was corrected. The importance of reduced cell number was discussed.

The aim of this study was to determine whether excessive weight gain in the first six weeks, three months, or six months of life was correlated. with overweight and obesity at the age of 6 to 8 years. One hundred and thirty eight infants with excessive weight gain in the first six months of life, 53 children with slow weight gain, and 33 children with an average weight gain were re-examined at the age of 6, 7, or 8 years.The mean height and weight of children who had gained weight rapidly in infancy were significantly higher than those of children who had gained weight slowly; those of infants whose weight gain had been average fell in between. The number of obese children in the rapid-weight-gain group was significantly higher than that of the combined average and slow-weight-gain groups. The rapidity of weight gain in infancy was a better guide to the risk of overweight in later childhood than the weight of the parents.

Abstract 811 Introduction: Vorinostat (VOR), an oral inhibitor of histone deacetylase class I and class II proteins, regulates genes and proteins involved in tumor growth and survival. The synergistic effects of VOR and bortezomib (BTZ) have been shown in preclinical studies and were confirmed in independent phase 1 trials in patients with relapsed/refractory multiple myeloma (MM), producing objective response rates (ORRs) of up to 42% and overall clinical benefit of up to 90%. Materials and methods: Eligible patients were aged ≥ 18 years, had measurable secretory MM, had received 1 to 3 prior systemic anti-myeloma regimens, and had an Eastern Cooperative Oncology Group status ≤ 2. Previous exposure to BTZ and the presence of extracellular plasmacytoma were allowed per protocol, but patients with prior resistance to BTZ were excluded. Patients were randomized 1:1 to receive 21-day cycles of BTZ (1.3 mg/m2 intravenously; days 1, 4, 8, and 11) in combination with oral VOR 400 mg/d, or matching placebo, on days 1 to 14. Additional use of corticosteroids for the treatment of MM was not allowed during the trial. Patients were treated until disease progression, unacceptable toxicities, or withdrawal from the study. The primary endpoint for this trial was progression-free survival (PFS; occurrence of 412 PFS events). Secondary and exploratory endpoints included ORR (≥ partial response), clinical benefit response (ORR + minimal response), overall survival, time to progression, patient-reported outcomes questionnaires (QLQ-C30, QLQ-MY20), and safety/tolerability of this novel drug combination. Responses and progression were determined according to the European Bone and Marrow Transplantation Group criteria and will be confirmed by an Independent Adjudication Committee. Results: Between January 2009 and January 2011, 637 patients were enrolled from 174 centers in 33 countries across the globe making this trial one of the largest studies conducted in patients with relapsed/refractory myeloma. Median age of the study population was 62 years (range, 29–86 years). Of the enrolled patients, 59% were male and 56% were Caucasian. Patients had received a median of 2 prior regimens (range, 1–3). Prior anti-myeloma agents included BTZ (24%), thalidomide (56%), lenalidomide (13%), melphalan (56%), and stem cell transplantation (35%). As of July 2011, 635 patients had received study medication, with a median exposure of 7 cycles (mean: 7.6 cycles; range 1–30 cycles). Reported median exposure to BTZ monotherapy in previous phase 3 trials was approximately 5 cycles. Conclusions: The study passed the protocol-specified futility analyses by the independent data monitoring committee in November 2010. Database lock is anticipated in November 2011, and top-line data on primary and secondary endpoints will be available at the meeting. Disclosures: Dimopoulos: Celgene, Ortho-Biotech: Consultancy, Honoraria. Off Label Use: Vorinostat, an inhibitor of histone deacetylase, is approved in the US for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat is currently under investigation for the treatment of relapsed malignant pleural mesothelioma, relapsed/refractory B cell lymphoma (in combination with other chemotherapy agents), and relapsed/refractory multiple myeloma (in combination with bortezomib and other chemotherapy agents). Jagannath:Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees. Yoon:Celgene: Consultancy; NK Bio: Consultancy. Siegel:Millennium: Honoraria, Research Funding, Speakers Bureau; Merck: Honoraria. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy. Hajek:Celgene: Honoraria; Janssen: Honoraria; Merck: Educational lecture. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees. Rosiñol:Celgene: Honoraria; Janssen-Cilag: Honoraria. Blacklock:New Zealand Bone Marrow Donor Registry: Consultancy, Employment; Mercy Hospital, Auckland New Zealand: Consultancy; Leukaemia and Blood Foundation, New Zealand: Consultancy, Membership on an entity's Board of Directors or advisory committees; Middlemore Hospital: Employment, Research Funding. Goldschmidt:Amgen, Novartis, Chugai: Research Funding; Janssen-Cilag, Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palumbo:Merck: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Reece:Merck: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding. Graef:Merck: Employment. Houp:Merck Research Laboratories: Employment. Sun:Merck & Co., Inc.: Employment. Eid:Merck Research Laboratories: Employment. Anderson:Celgene: Consultancy; Millennium: Consultancy; Novartis: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy; Acetylon: founder.

We report the electrochemical behavior of various layered oxides in Li cells. A series of LiNiyMnyCozO2 materials (with z=1-2y) was synthesized by “chimie douce” and investigated as positive electrodes in rechargeable lithium batteries. Electrochemical performances of LiNiyMnyCozO2 oxides are tested cell using non-aqueous 1M LiPF6 dissolved in EC-DEC. Charge discharge profiles are investigated as a function of the rate capability, the voltage window and the synthesis parameters of the cathode. A relation is found between the gravimetric capacity and the cation disorder of materials as indicated by magnetometry analysis.

The kinetics of the solvolysis of the cation cis-[Co(en)2SCNCl]+ have been investigated in water–t-butyl alcohol mixtures (en = 1,2-diaminoethane). The linear variation of log (rate constant) with the reciprocal of the dielectric constant expected when solvent structure has little influence on the kinetics is not found, and the enthalpy and entropy of activation both show extrema in the same regions of solvent composition where the physical properties of the mixtures influenced by changes in solvent structure also show extrema. By applying a free-energy cycle to the solvolysis in water and in the mixture, it is concluded that the effect of changes in solvent structure have a greater influence on the pentacoordinated cobalt(III) cation in the transition state than on the hexacoordinated cation in the initial state. By using data for the free energy of transfer of [Co(en)2SCNCl]+ between water and the solvent mixtures, free energies of transfer for [Co(en)2SCN]2+ have been calculated from the free-energy cycle. These results are compared with those for the solvolysis of the same ion in water–propan-2-ol mixtures and for the solvolysis of a range of coordinated cobalt(III) ions in mixtures of water with a range of alcohols.

Rates of the first-order solvolysis of 1,2-chlorothiocyanatobis(1,2-diaminoethane)cobalt(III) ions have been measured for a range of temperatures in water and in water + propan-2-ol. A plot of log (rate constant) against the Y factor is linear, but a plot of log (rate constant) against the reciprocal of the dielectric constant is curved. From a comparison of the variation of the enthalpy and entropy of activation with the physical properties of the solvent mixture it is concluded that solvent structure is an important factor determining solvolytic reactivity. The evidence currently available concerning the nature of the transition state in substitution reactions and, in particular, the solvolytic transition states of CoIII complexes is assessed. The influence of values for the free energy of transfer of ions on the assignment of the contributions of solvent structure to the initial and transition states for substitution reactions is discussed. As a result of the application of a free-energy cycle relating the process initial state → transition state in water to that in the mixture, it is concluded that the influence of solvent structure predominates on the pentacoordinated cation in the transition state over its influence on the hexacoordinated cation in the initial state.

Rates of solvolysis of the 1,2-chloroazido-bis(ethylenediamine)cobalt(III) ion have been measured in water and in water + isopropanol in the composition range mole fraction of isopropanol 0–0.2. Although log (rate constant) varies linearly with the reciprocal of the dielectric constant, comparison with other co-solvents shows that the slope of these plots varies with the co-solvent used. The influence of solvent structure on the reaction is shown by comparing the variation with solvent composition of the transition-state parameters for the solvolysis with the physical properties of the solvent mixture. The application of a free-energy cycle to the loss of the Cl– in the transition state shows that changes in solvent structure have a much greater effect on the transition state than on the initial state.