Simultaneous memory effects in the stress and in the dielectric susceptibility of a stretched polymer glass.

We report experimental evidence that a polymer stretched at constant strain rate λ[over ̇] presents complex memory effects after λ[over ̇] is set to zero at a specific strain λ_{w} for a duration t_{w}, ranging from 100s to 2.2×10^{5}s. When the strain rate is resumed, both the stress and the dielectric constant relax to the unperturbed state nonmonotonically. The relaxations depend on the observable, on λ_{w} and on t_{w}. Relaxation master curves are obtained by scaling the time and the amplitudes by ln(t_{w}). The dielectric evolution also captures the distribution of the relaxation times, so the results impose strong constraints on the relaxation models of polymers under stress and they can be useful for a better understanding of memory effects in other disorder materials.

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

BACKGROUND: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.

The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation.

We thought that the rate of postoperative pulmonary complications might be higher after pressure-controlled ventilation than after volume-controlled ventilation. We analysed peri-operative data recorded for 109,360 adults, whose lungs were mechanically ventilated during surgery at three hospitals in Massachusetts, USA. We used multivariable regression and propensity score matching. Postoperative pulmonary complications were more common after pressure-controlled ventilation, odds ratio (95%CI) 1.29 (1.21-1.37), p < 0.001. Tidal volumes and driving pressures were more varied with pressure-controlled ventilation compared with volume-controlled ventilation: mean (SD) variance from the median 1.61 (1.36) ml.kg-1 vs. 1.23 (1.11) ml.kg-1 , p < 0.001; and 3.91 (3.47) cmH2 O vs. 3.40 (2.69) cmH2 O, p < 0.001. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at positive end-expiratory pressures < 5 cmH2 O was 1.40 (1.26-1.55) and 1.20 (1.11-1.31) when ≥ 5 cmH2 O, both p < 0.001, a relative risk ratio of 1.17 (1.03-1.33), p = 0.023. The odds ratio (95%CI) of pulmonary complications after pressure-controlled ventilation compared with volume-controlled ventilation at driving pressures of < 19 cmH2 O was 1.37 (1.27-1.48), p < 0.001, and 1.16 (1.04-1.30) when ≥ 19 cmH2 O, p = 0.011, a relative risk ratio of 1.18 (1.07-1.30), p = 0.016. Our data support volume-controlled ventilation during surgery, particularly for patients more likely to suffer postoperative pulmonary complications.

Role of Dynamical Heterogeneities on the Mechanical Response of Confined Polymer.

Confinement induces various modifications in the dynamics of polymers as compared to bulk. We focus here on the role of dynamical heterogeneities on the mechanics of confined polymers. Using a simple model that allows computation of the mechanical response over 10 decades in frequency, we show that the local mechanical coupling controlling the macroscopic response in the bulk disappears in a confined geometry. The slowest domains significantly contribute to the mechanical response for increasing confinement. As a consequence, the apparent glass transition is broadened and shifted towards lower frequencies as confinement increases. We compare our numerical predictions with experiments performed on poly(ethylacrylate) chains in model filled elastomers. We suggest that the change of elastic coupling between domains induced by confinement should contribute significantly to the polymer mobility shift observed on filled systems.

Long-time damage under creep experiments in disordered materials: transition from exponential to logarithmic fracture dynamics.

Some materials, and in particular some polymer materials, can display an important range of stress levels for which slow and progressive damage can be observed before they finally break. In creep or fatigue experiments, final rupture can happen after very long times, during which the mechanical properties have progressively decayed. We model here some generic features of the long-time damage evolution of disordered elastic materials under constant load, characterized by a progressive decrease of the elastic modulus. We do it by studying a two-dimensional electric random fuse network with quenched disorder and thermal noise. The time evolution of global quantities (conductivity or, equivalently, elastic modulus) is characterized by different regimes ranging from faster than exponential to slower than logarithmic, which are governed by the stress level and the relative magnitude of disorder with respect to temperature. A region of widely distributed rupture times exists where the modulus decays (more slowly than) logarithmically for not too small values of the disorder and for not too large values of the load. A detailed analysis of the dynamical regimes is performed and presented through a phase diagram.

Mechanical properties of thin confined polymer films close to the glass transition in the linear regime of deformation: theory and simulations.

Over the past twenty years experiments performed on thin polymer films deposited on substrates have shown that the glass transition temperature T(g) can either decrease or increase depending on the strength of the interactions. Over the same period, experiments have also demonstrated that the dynamics in liquids close to the glass transition temperature is strongly heterogeneous, on the scale of a few nanometers. A model for the dynamics of non-polar polymers, based on percolation of slow subunits, has been proposed and developed over the past ten years. It proposes a unified mechanism regarding these two features. By extending this model, we have developed a 3D model, solved by numerical simulations, in order to describe and calculate the mechanical properties of polymers close to the glass transition in the linear regime of deformation, with a spatial resolution corresponding to the subunit size. We focus on the case of polymers confined between two substrates with non-negligible interactions between the polymer and the substrates, a situation which may be compared to filled elastomers. We calculate the evolution of the elastic modulus as a function of temperature, for different film thicknesses and polymer-substrate interactions. In particular, this allows to calculate the corresponding increase of glass transition temperature, up to 20 K in the considered situations. Moreover, between the bulk T(g) and T(g) + 50 K the modulus of the confined layers is found to decrease very slowly in some cases, with moduli more than ten times larger than that of the pure matrix at temperatures up to T(g) + 50 K. This is consistent with what is observed in reinforced elastomers. This slow decrease of the modulus is accompanied by huge fluctuations of the stress at the scale of a few tens of nanometers that may even be negative as compared to the solicitation, in a way that may be analogous to mechanical heterogeneities observed recently in molecular dynamics simulations. As a consequence, confinement may result not only in an increase of the glass transition temperature, but in a huge broadening of the glass transition.

Thiamine, riboflavin, folate, and vitamin B12 status of infants with low birth Weights receiving enteral nutrition.

The purpose of the present study was to monitor the vitamin status of 14 low-birth-weight (LBW) infants (< 1,750 g birth weight) at 2 weeks and an additional four infants at 3 weeks who were receiving an enteral formula providing 247 micrograms/100 kcal thiamine, 617 micrograms/100 kcal riboflavin, 37 micrograms/100 kcal folate, and 0.55 micrograms/100 kcal vitamin B12. The mean birth weight of the 18 infants was 1,100 +/- 259 g, and mean gestational age was 29 +/- 2 weeks. Weekly blood, 24-h urine collections, and dietary intake data were obtained. For thiamine, red blood cell (RBC) transketolase activity was within the normal range for all infants. For riboflavin, RBC glutathione reductase activity was normal for all infants except one. We calculated from intake and urinary excretion data that these infants require 225 micrograms/100 kcal thiamine and 370 micrograms/100 kcal riboflavin, respectively. Mean plasma folate levels were 21 +/- 11 ng/ml at 2 weeks and 18 +/- 5 ng/ml at 3 weeks. RBC folate levels were 455 +/- 280 ng/ml at 2 weeks and 391 +/- 168 ng/ml at 3 weeks. All folate blood values were normal, except for one subject with an elevated level (59 ng/ml). Vitamin B12 plasma values were 737 +/- 394 pg/ml at 2 weeks and 768 +/- 350 pg/ml at 3 weeks, and all values were normal except for three infants with elevated values. In conclusion, appropriate vitamin status was maintained during this short observational period, during administration of this enteral formula; however, riboflavin concentrations in the enteral feed may be excessive.

Intravenous iron administration to very-low-birth-weight newborns receiving total and partial parenteral nutrition.

BACKGROUND: Intravenous iron supplements are not routinely administered to very-low-birth-weight newborns receiving total parenteral nutrition because of the possible increased risk of infection and because iron needs may be met with blood transfusions. METHODS: To assess the benefits of a prudent IV iron supplement (200 to 250 micrograms/kg/d), 26 very-low-birth-weight newborns (birth weight, 1005 +/- 302 g; gestational age, 28 +/- 2.3 weeks; mean +/- SD) were randomly allocated to receive total parenteral nutrition without iron (No-Iron) or with iron supplied as iron dextran (Iron). These newborns were followed at baseline (2 to 3 days after birth) and at weeks 1 to 4 thereafter. At each sampling time, urine samples, fecal samples (rarely), unused total parenteral nutrition solutions, blood products, and a blood sample (1 mL) were collected. RESULTS: There were no differences between the two groups in anthropometric measurements, hematologic or biochemical parameters, number or amount of blood transfusions (2.3 +/- 1.9), amount of blood removed for diagnostic purposes (44 +/- 16 mL), or number of septic events (n = 16). There was no difference between the groups for the total iron excreted; however, the Iron group retained more iron. Iron balance was negative for all but 10 newborns (No-Iron, 3; Iron, 7) throughout the study. CONCLUSIONS: A total iron intake of 400 micrograms/kg/d, half of which was provided by IV iron, is not sufficient to maintain iron balance or to meet fetal accretion rates (1000 micrograms/kg/d) in very-low-birth-weight newborns receiving total parenteral nutrition. Furthermore, endogenous iron from blood transfusions does not provide an adequate supply of iron.

Selenium status of very low birth weight infants.

The selenium (Se) intake and status of 82 very low birth weight infants (birth weight 1110 +/- 286 g, gestational age 29.2 +/- 3 wk, mean +/- SD) was assessed at 36.3 +/- 3 postconceptional wk, at 40.1 +/- 4 wk (hospital discharge), and at 3, 6, 9, and 12 +/- 0.75 mo corrected for gestational age. Infants were fed formula containing 0.13 mumol/L (10 micrograms/L) Se. Se-dependent glutathione peroxidase activity in red blood cells declined corresponding to low Se intakes (micrograms/kd/d) for the first 6 mo. With increased consumption of solid foods, intakes of dietary Se and Se-dependent glutathione peroxidase activity increased at 9 mo, suggesting that the earlier supply of Se was suboptimal. Se-dependent glutathione peroxidase activity and intakes of Se were lower in males than in females (p < 0.05). We suggest that infant formulas should probably contain 0.26-0.33 mumol/L (20-25 micrograms/L) Se, particularly those formulas consumed by very low birth weight infants.

Zinc supplementation in very-low-birth-weight infants.

Inadequate zinc intake may lead to poor growth and developmental outcome in very-low-birth-weight (VLBW; < 1,500 g) infants. Fifty-two infants (mean birth weight, 1,117 +/- 287 g; mean gestational age, 29 +/- 2.9 weeks) were randomly allocated to two groups. SUPP infants received a regular term formula plus zinc supplements (4.4 mg/L; final content, 11 mg/L); PLAC infants received the same formula plus placebo (final content, 6.7 mg/L). Infants started their formula at 1,853 +/- 109 g and consumed the formula for 6 months. All subjects were evaluated at 3, 6, 9, and 12 +/- 0.75 months corrected-for-gestational-age. At each evaluation, weight, length, and head circumference were measured, a Griffiths developmental assessment was performed, and a blood sample was taken. Higher plasma zinc levels (p < 0.05) were found in the SUPP group at 1 and 3 months, and improved linear growth velocity was found in the SUPP group over the study period for the whole group as well as for girls alone. Maximum motor development scores were higher (p = 0.018) in the SUPP (98 +/- 10) than the PLAC (90 +/- 8) group, indicating that increased zinc intake in early infancy may be beneficial to VLBW infants.

The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia.

Sequential methotrexate (Mtx) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia (ALL) to determine whether serum drug concentration, clearance and dosage affect event free survival (EFS). Higher serum concentration and area under the plasma concentration curve (AUC) were not associated with an improved EFS. Methotrexate clearance was not found to be of prognostic significance. Patients who tolerated only low 6-mercaptopurine (6-MP) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy. This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL.

Iron status of very-low-birth-weight infants during the first 15 months of infancy.

The adequacy of iron stores in infants of very low birth weight (defined as less than 1500 g) in Canada is unknown. We monitored the iron status of 81 such infants at 3, 6, 9, 12 and 15 months of age. All of the infants were fed formula fortified with iron (13 mg/L) for at least 6 months, starting at 2 months of age. The plasma ferritin level decreased after the formula was no longer used. Although 90% of the infants were given cereal fortified with iron (30 mg of iron per 100 g) by 9 months of age, the plasma ferritin level continued to decrease. The level was less than 10 micrograms/L in 54% of the infants at 12 months of age and in 74% at 15 months; this indicated depleted iron stores. Because of delayed development very-low-birth-weight infants eat small amounts of cereal and therefore require iron-fortified formula throughout infancy.

X-ray sensitivity of fibroblasts from patients with hereditary retinoblastoma and their families.

The in vitro response to X-irradiation of cultured human fibroblasts was studied using a colony forming assay. A comprehensive reference range was established, giving a median D0 value of 98.5 cGy with an interquartile range of 86.5-110.5 cGy. Cells from 3 retinoblastoma family pedigrees were studied and the cell survival after exposure to X-rays was compared between affected (11 samples) and unaffected (26 samples) family members. No significant differences in response to ionising radiation were found between the controls, the affected and the unaffected members of the 3 families. The affected members had a median D0 of 97.5 cGy (interquartile range 87.5-107.5 cGy) and the unaffected members had a median D0 of 102 cGy (interquartile range 93-111 cGy). Thus radiosensitivity is not a useful marker for the detection of the retinoblastoma gene.

A comparison of energy substrates and reproductive patterns of two anurans. Acris crepitans and Bufo woodhousei.

The seasonal pattern of carcass, liver and ovary lipid and liver non-lipid mass was examined in the cricket frog, Acris crepitans, and Woodhouse's toad, Bufo woodhousei. Reproductive patterns were also studied. The over-winter reduction of body lipid and liver non-lipid material was attributed to metabolism in Acris crepitans. Male, but not female, Bufo woodhousei exhibited seasonal variation in lipid stores that was attributable to metabolism. Females, but not males, showed seasonal variation in liver non-lipid mass and quantified liver glycogen. Females of both species mobilized body lipid during the period of ovarian development; however, an inverse relationship between fatbody mass and ovary mass was evident for Acris, only. Female Acris crepitans depleted all ovarian follicles prior to brumation; however, Bufo woodhousei retained enlarged follicles throughout the year. Variation in metabolic substrate use between species was related to the differences in reproductive patterns exhibited by the two anurans. These variations in reproductive strategy represent adaptations that enhance the survivability of different species in dissimilar habitats.

Virus infections in childhood malignant disease.

The viruses isolated during infective episodes over a 5-year period of 93 children with acute lymphoblastic leukemia (ALL) and 107 children with other malignancies have been studied. Viruses were identified by the fluorescent antibody technique (FAT), electron microscopy, and culture. Viruses were isolated on 204 occasions. Rhinovirus and RSV occurred significantly more often in the patients with ALL, and adenovirus more commonly in the solid tumor patients. Viruses were responsible for 4 of the 69 deaths. Multiple different virus isolation during the same infective episode was significantly more common than in a control group. Where paired sera were available, only 10 out of 27 children showed at least a fourfold rise to the isolated virus. A rise in complement-fixing antibody is confirmed as a very unreliable method of detecting virus infection in immunosuppressed children. Viruses are important pathogens in children with cancer and assume greater relevance now that over 60% of malignant disease in childhood can be cured.

Pharmacokinetics of oral and intramuscular methotrexate in children with acute lymphoblastic leukaemia.

Repeated methotrexate absorption studies were performed under standard conditions in 127 children receiving either oral or intramuscular methotrexate for acute lymphoblastic leukaemia. There was marked variability in peak concentration, area under the serum concentration curve and clearance both between patients and in repeated studies on the same patient. Although the intramuscular route produced higher serum concentrations and AUC than the oral route, variability within and between patients was considerable and was most marked at higher concentrations. Neither age or sex could account for variation in methotrexate absorption or clearance. Intramuscular methotrexate, although producing higher serum concentrations and AUC, does not reduce the variability observed with oral administration. Prediction of subsequent methotrexate concentrations from the knowledge of one absorption profile is not possible.

Immunogenetic studies in retinoblastoma.

In three unrelated families with transmitted retinoblastoma 43 members were tested for HLA-A, B, C, and DR antigens. On 18 patients, 16 unaffected relatives, and 16 controls, mixed lymphocyte cultures were carried out and the response to mitogens, phytohaemagglutinin, concanavalin A, and pokeweed mitogen examined. There were no associations of retinoblastoma with any HLA antigen. A reduction in T cell function is suggested by the results of the mitogen tests.

Elevated testosterone level in response to clomiphene in male Anolis carolinensis.

Anolis carolinensis were used as experimental models to study the short-term effects of the fertility drug, clomiphene citrate, on male squamate reproductive function. Daily injections of 10.0 micrograms of clomiphene induced an increase in plasma testosterone over a 5 day period. No change in testis mass or morphology was elicited over this time.