Temperature dependence of micelle shape transitions in copolymer solutions: the role of inter-block incompatibility.

The nature of the transition between worm-like and spherical micelles in block copolymer dispersions varies between systems. In some formulations, heating drives a transition from worms to spheres, while in other systems the same transition is induced by cooling. In addition, a sphere-worm interconversion can be accompanied either by an increase or a decrease in the core solvation, even if the direction of the temperature dependence is the same. Here, self-consistent field theory is used to provide a potential explanation of this range of behaviour. Specifically, we show that, within this model, the dependence of the transition on the incompatibility χBS of the solvophobic block B and the solvent S (the parameter most closely related to the temperature) is strongly influenced by the incompatibility χAB between B and the solvophilic block A. When χAB is small (χAB < 0.1), it is found that increasing χBS produces a transition from worm-like micelles to spheres (or, more generally, from less curved to more curved structures). When χAB is above 0.1, increasing χBS drives the system from spheres to worm-like micelles. Whether a transition is observed within a realistic range of χBS is also found to depend on the fraction of solvophilic material in the copolymer. The relevance of our calculations to experiments is discussed, and we suggest that the direction of the temperature dependence may be controlled not only by the solution behaviour of the solvophobic block (upper critical solution temperature-like versus lower critical solution temperature-like) but also by χAB.

Heterotelechelic homopolymers mimicking high χ - ultralow N block copolymers with sub-2 nm domain size.

Three fluorinated, hydrophobic initiators have been utilised for the synthesis of low molecular mass fluoro-poly(acrylic acid) heterotelechelic homopolymers to mimic high chi (χ)-low N diblock copolymers with ultrafine domains of sub-2 nm length scale. Polymers were obtained by a simple photoinduced copper(ii)-mediated reversible-deactivation radical polymerisation (Cu-RDRP) affording low molecular mass (<3 kDa) and low dispersity (D = 1.04-1.21) homopolymers. Heating/cooling ramps were performed on bulk samples (ca. 250 µm thick) to obtain thermodynamically stable nanomorpologies of lamellar (LAM) or hexagonally packed cylinders (HEX), as deduced by small-angle X-ray scattering (SAXS). Construction of the experimental phase diagram alongside a detailed theoretical model demonstrated typical rod-coil block copolymer phase behaviour for these fluoro-poly(acrylic acid) homopolymers, where the fluorinated initiator-derived segment acts as a rod and the poly(acrylic acid) as a coil. This work reveals that these telechelic homopolymers mimic high χ-ultralow N diblock copolymers and enables reproducible targeting of nanomorphologies with incredibly small, tunable domain size.

The Efficacy and Safety of Additional Anti-HER2-Targeting Drugs in the Treatment of HER2-Positive Advanced Breast Cancer: A Meta-Analysis.

BACKGROUND: HER2-positive breast cancer patients account for one-fifth of the total breast cancer population. Besides, more anti-HER2-targeting drugs have appeared clinically. OBJECTIVE: This study aimed to analyze the efficacy and safety of additional anti-HER2 (Human Epidermal growth Factor Receptor 2)-targeting drugs in the treatment of HER2-positive advanced breast cancers. METHODS: The following databases were searched for published articles containing data on the efficacy and safety of additional anti-HER2-targeting drugs in HER2-positive advanced breast cancer from the time of their inception until December 2019: PubMed, Web of Science, EBSCO, and Cochrane library. The primary outcomes were Progression-Free Survival (PFS) and Overall Survival (OS). RESULTS: The additional anti-HER2-targeting drugs significantly improved the PFS (HR: 0.66, p<0.001) and OS (HR: 0.77, p<0.001) of HER2-positive advanced breast cancer patients. Regarding drug types, lapatinib was the most effective (HR: 0.53, 95% Cl: 0.39-0.67, p<0.001), followed by pertuzumab (HR: 0.72, 95% Cl: 0.55-0.89, p=0.001). Trastuzumab was the least beneficial (HR: 0.87, 95% Cl: 0.31-1.44, p=0.594). Concerning treatment regimen, first-line treatment (HR: 0.67, 95% Cl: 0.52-0.82, p<0.001) was more effective than non-first-line treatment (HR: 0.82, 95% Cl: 0.71-0.94, p=0.004). The main Adverse Events (AEs) observed were diarrhea and decreased ejection fraction. CONCLUSION: Additional anti-HER2-targeting drugs can improve long-term prognosis in HER2-positive advanced breast cancers. Besides, they are associated with fewer AEs and are tolerable. Lapatinib is the most effective drug, followed by pertuzumab, whereas trastuzumab is the least effective. Concerning treatment, we recommend the use of anti-HER2-targeting drugs in first-line therapy of HER2-positive advanced breast cancers.

Synthesis and pH-responsive dissociation of framboidal ABC triblock copolymer vesicles in aqueous solution.

A series of pH-responsive all-methacrylic ABC triblock copolymer vesicles were prepared from precursor diblock copolymer vesicles via RAFT seeded emulsion polymerisation. Microphase separation between the two hydrophobic membrane-forming B and C blocks produced a distinctive framboidal morphology, for which the mean globule size can be tuned by adjusting the triblock copolymer composition. These vesicles remain intact at neutral pH, but undergo irreversible dissociation on addition of acid as a result of protonation of the tertiary amine groups located within the third block. Small-angle X-ray scattering (SAXS) was utilised to characterise the morphologies formed at pH 8 and pH 3. According to time-resolved SAXS studies, the acid-induced dissociation of these pH-responsive framboidal vesicles involves appreciable membrane swelling within 50 ms and is complete.

ABC Triblock Copolymer Worms: Synthesis, Characterization, and Evaluation as Pickering Emulsifiers for Millimeter-Sized Droplets.

Polymerization-induced self-assembly (PISA) is used to prepare linear poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate)-poly(benzyl methacrylate) [PGMA-PHPMA-PBzMA] triblock copolymer nano-objects in the form of a concentrated aqueous dispersion via a three-step synthesis based on reversible addition-fragmentation chain transfer (RAFT) polymerization. First, GMA is polymerized via RAFT solution polymerization in ethanol, then HPMA is polymerized via RAFT aqueous solution polymerization, and finally BzMA is polymerized via "seeded" RAFT aqueous emulsion polymerization. For certain block compositions, highly anisotropic worm-like particles are obtained, which are characterized by small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). The design rules for accessing higher order morphologies (i.e., worms or vesicles) are briefly explored. Surprisingly, vesicular morphologies cannot be accessed by targeting longer PBzMA blocks-instead, only spherical nanoparticles are formed. SAXS is used to rationalize these counterintuitive observations, which are best explained by considering subtle changes in the relative enthalpic incompatibilities between the three blocks during the growth of the PBzMA block. Finally, the PGMA-PHPMA-PBzMA worms are evaluated as Pickering emulsifiers for the stabilization of oil-in-water emulsions. Millimeter-sized oil droplets can be obtained using low-shear homogenization (hand-shaking) in the presence of 20 vol % n-dodecane. In contrast, control experiments performed using PGMA-PHPMA diblock copolymer worms indicate that these more delicate nanostructures do not survive even these mild conditions.

Vermicious thermo-responsive Pickering emulsifiers.

Thermo-responsive vermicious (or worm-like) diblock copolymer nanoparticles prepared directly in n-dodecane via polymerisation-induced self-assembly (PISA) were used to stabilise water-in-oil Pickering emulsions. Mean droplet diameters could be tuned from 8 to 117 µm by varying the worm copolymer concentration and the water volume fraction and very high worm adsorption efficiencies (∼100%) could be obtained below a certain critical copolymer concentration (∼0.50%). Heating a worm dispersion up to 150 °C led to a worm-to-sphere transition, which proved to be irreversible if conducted at sufficiently low copolymer concentration. This affords a rare opportunity to directly compare the Pickering emulsifier performance of chemically identical worms and spheres. It is found that the former nanoparticles are markedly more efficient, since worm-stabilised water droplets are always smaller than the equivalent sphere-stabilised droplets prepared under identical conditions. Moreover, the latter emulsions are appreciably flocculated, whereas the former emulsions proved to be stable. SAXS studies indicate that the mean thickness of the adsorbed worm layer surrounding the water droplets is comparable to that of the worm cross-section diameter determined for non-adsorbed worms dispersed in the continuous phase. Thus the adsorbed worms form a monolayer shell around the water droplets, rather than ill-defined multilayers. Under certain conditions, demulsification occurs on heating as a result of a partial worm-to-sphere morphological transition.

Regulation of poly(A)-binding protein through PABP-interacting proteins.

Translation initiation requires the participation of eukaryotic translation initiation factors (eIFs). The poly(A)-binding protein (PABP) is thought to stimulate translation by promoting mRNA circularization through simultaneous interactions with eIF4G and the 3' poly(A) tail. PABP activity is regulated by the PABP-interacting proteins (Paips), a family of proteins consisting of Paip1, a translational stimulator, and Paip2A and Paip2B, two translational inhibitors. Paip2A controls PABP homeostasis via ubiquitination. When the cellular concentration of PABP is reduced, Paip2A becomes ubiquitinated and degraded, resulting in the relief of PABP repression. Paip1 interacts with eIF4A and eIF3, which promotes translation. The regulation of PABP activity by Paips represents the first known mechanism for controlling PABP, adding a new layer to the existing knowledge of PABP function.

Conflicts between young adolescents with type I diabetes and their parents.

ISSUES AND PURPOSE: The purposes were to describe sources of parent-adolescent conflict in families of young adolescents with type I diabetes and to determine if the sources of conflict were similar to those in a comparable nondistressed group from an earlier study. DESIGN AND METHODS: A descriptive study of 161 adolescents with type I diabetes and their parents examined conflict using the Issues Checklist. RESULTS: Adolescents with type I diabetes and their families were similar to a non-distressed population in their ranking of quantity, intensity, and frequency by intensity scores. Issues generating the highest frequency of discussion were comparable to those reported in the nondistressed group, with the exception of topics regarding what time to have meals and to watch television. Intensity of discussion was also comparable, with the exception of topics regarding getting up in the morning and bothering the parents. Adolescent report of conflict with the mother was significantly lower overall for the adolescents with type I diabetes. PRACTICE IMPLICATIONS: Conflict is expected between young adolescents and parents, and having type I diabetes does not heighten conflict with parents with respect to general adolescent issues. Understanding this principle should help healthcare workers recognize usual adolescent-parent conflict and use similar approaches to address these conflicts as are used with nondistressed families.

Stress-point intervention for parents of repeatedly hospitalized children with chronic conditions.

Little is known about how to assist children with chronic conditions and their families cope with repeated hospitalizations. A two-group, pretest-posttest study was done to determine whether a community-based, stress-point nursing intervention for parents could decrease distress and improve child and family functioning. Fifty participants were randomly assigned to intervention or usual care control groups. The intervention focused on specific, parent-verified child and family issues. Three months after hospitalization, intervention parents had better coping and family functioning than those in the usual care group. Intervention parents' anxiety was initially higher and then lower. There were no child behavior differences between the groups after hospitalization. Intervention children had no developmental regression at 2 weeks and better developmental gains 3 months after discharge than the usual care children. Stress-point intervention for families and their children with chronic conditions improved family coping and functioning, and eliminated hospitalization-induced developmental regression.

Intrapartum fetal asphyxia and the occurrence of minor deficits in 4- to 8-year-old children.

Term newborn infants, 48 of whom had mild intrapartum fetal asphyxia, and 43 controls were assessed between 4 and 8 years of age for evidence of selective brain damage and minor deficits. Measures of motor and cognitive development were obtained at 4 and at 6 to 8 years of age. Memory tests, including the Alternation Test and determinations of Extended Digit Span, Spatial Memory, and Paired Associate Learning, were given annually between 4 and 8 years of age. Assessments of the family, child health, and child behaviour were obtained. There were no differences between the asphyxia and control groups for motor or cognitive development or the serial tests of memory. The two groups did not differ in regard to family characteristics, child health, or child behaviour. These findings indicate that term newborn infants exposed to mild intrapartum fetal asphyxia do not have minor motor and cognitive deficits later in childhood.

Incidence of sudden infant death syndrome in infants with sickle cell trait.

The significantly higher incidence of both sickle cell trait (SCT) and sudden infant death syndrome (SIDS) in the black population suggests that SCT and SIDS may be epidemiologically related. To study this possibility, we identified, for the period of February 1990 to February 1992, all infants with SCT born in Los Angeles County whose disease was diagnosed through the California Newborn Screening Program. We matched these infants with all confirmed cases of SIDS in Los Angeles County from February 1990 to March 1993. Three cases of SCT among 589 infants confirmed to have had SIDS were identified. The incidence of SIDS was 1.25/1000 live births for the general population versus 0.58/1000 cases for the SCT group. This finding remained unchanged when rates were adjusted for ethnicity. We conclude that infants born with SCT are not at increased risk of dying of SIDS.

The evaluation and treatment of sleep disturbances in young children.

This study examines the accuracy of parents' reports about their children's sleep behavior and their response to a behavioral treatment. Twenty-eight sleep-disordered and thirty control children aged 12-36 months were filmed during three nights using an infrared camera and their sleep behavior compared with parental reports. There were significant differences among the groups with parents of good sleepers being less accurate in reporting on their children's sleep behavior. Poor sleepers also had more behavior problems, a more difficult temperament and more adverse early medical histories. The good sleepers woke up as frequently as the poor sleepers. However, they managed to soothe themselves back to sleep without disturbing anyone. Virtually all poor sleepers showed significant improvement following treatment.

Association of intrauterine fetal growth retardation and learning deficits at age 9 to 11 years.

OBJECTIVE: We examined the association of fetal and newborn complications, socioeconomic status, and home environment with learning deficits as assessed between 9 and 11 years of age. STUDY DESIGN: A total of 218 high-risk newborns have been assessed at 1, 4, and 9 to 11 years of age. Fetal and newborn complications included 77 newborns with growth retardation. Socioeconomic variables included parental occupation and education. Outcome measures at 9 to 11 years included the Woodcock Reading Mastery Test and the Wide Range Achievement Test. Motor and cognitive development was assessed by a neurologic examination, the Bruininks-Oseretsky Test of Motor Proficiency, and the Wechsler Intelligence Scale for Children. Behavior was assessed with the Achenbach Child Behavior Check List and Connor's Teacher Rating Scale. RESULTS: Learning deficits were identified in 77 of the 218 children (35%). Children with learning deficits had lower full-scale IQ scores and behavioral problems of inattention and anxiety. Both fetal growth retardation and the father's occupation score were independently associated with these learning deficits. CONCLUSION: Fetal growth retardation, socioeconomic status, and behavioral characteristics of inattention and anxiety are associated with less favourable academic achievement at 9 to 11 years of age.

Sudden infant death syndrome in infants of substance-abusing mothers.

A population-based study was performed to determine whether substance abuse during the perinatal period may be a risk factor for sudden infant death syndrome (SIDS). The incidence of SIDS was studied in 2143 infants of substance-abusing mothers (ISAM) born in Los Angeles County during 1986 and 1987 who were reported to the Los Angeles County Department of Health Services because of a history of drug exposure or positive urine test results in the mother, infant, or both. By comparing the ISAM birth reports with records of autopsy-proven SIDS in Los Angeles County, we found 19 SIDS cases in the population of 2143 ISAM, a SIDS rate of 8.87 cases per 1000 ISAM (95% confidence interval 5.3 to 13.8). This was significantly higher than the SIDS rate for the non-ISAM general population: 396 SIDS deaths among 325,372 live births, an incidence rate of 1.22 cases per 1000 births, p less than 0.00001. The age of ISAM at death was 99 +/- 63 (mean +/- SD) days compared with 91 +/- 52 days for the non-ISAM population (not significant). The incidence of SIDS was significantly greater in male infants, during the winter months, in black infants, and in non-Hispanic white infants in the non-ISAM population. Such differences were not observed in the ISAM group. A greater incidence of symptomatic apnea was reported before SIDS for the ISAM than for the non-ISAM population (22% vs 5.4%, p = 0.022). We conclude that ISAM have a higher incidence of SIDS than the non-ISAM general population. However, it was not possible to separate maternal substance abuse from other confounding variables that may also have had an impact on SIDS risk in the ISAM group.

Mainstreaming children with handicaps: implications for pediatricians.

The judicial precedents and legislative mandates passed during the past two decades to ensure full appropriate public education for all children have resulted in a movement toward mainstreaming children with a wide range of physical and developmental disabilities into regular education classroom settings. Although some child development and pediatric literature has addressed the effects of these initiatives on the children with handicaps, less attention has been paid to the effect that mainstreaming has on their nondisabled peers in the classroom. As knowledgeable community advocates, pediatricians should be informed about the specifics of the mainstreaming movement. This paper outlines the movement's historical underpinnings, discusses current definitions of "mainstreaming", and briefly reviews the literature on the effects of this policy on classrooms, teachers, and students with and without disabilities. The impact of mainstreaming children with handicaps in regular classroom settings is equivocal, with many studies lacking methodological sophistication to yield reliable and valid data. Results of the few well-designed studies do show, however, that academic and social outcomes for both the handicapped child and for his/her nondisabled peers are consistently better in mainstreamed classrooms where adequate resources have been made available to the child and teacher than in more segregated settings. Furthermore, the literature consistently points out the key role both regular and special education teachers play in successful mainstreamed classrooms. Pediatricians can help families with children with disabilities negotiate the educational system in order to achieve the appropriate classroom placement.

Maternal stress and repeated hospitalizations of children who are physically disabled.

A quasi-experimental study (N = 60) found that the degree and nature of the parental stress experienced with repeated hospitalizations of physically disabled children was different from that experienced by a comparison group with nondisabled children. There was more community nurse support among those with lower versus higher stress over repeated hospitalizations. Next, using qualitative methods, parent and nurse groups validated and extended the findings to the issues involved in the chronic and complex source of stress. Thus, implications from research on single, brief hospitalizations of essentially healthy children may not apply to repeatedly hospitalized, disabled children and their parents.

Issues in the classification of children who fail in school: categorical versus descriptive approaches.

The classification of children who are failing in school has become a matter of national interest and concern since 1975 when the passage of PL 94-142 created a system of categories for designating the specific disorders which lead to the need for special education. This paper explores two trends in classification: namely, categorization and the descriptive approach. The benefits of categorization include the ability to create a national data base, from which epidemiologic and trend information are available; the ability to study local variation and relate this to intervention systems, and the ability to monitor the resources expended on special education. However, a number of liabilities are built into categorization system. The most serious of these is the fact that individual variation is not recognized by a categorical approach. Clinically, many multidisciplinary teams have preferred to provide parents and schools with descriptive classifications which take into account the variety of influences and symptoms at work in particular situations. Practical suggestions are offered in this paper to help pediatricians use both the categorical and descriptive approaches in helping parents as their children are diagnosed as a result of their school failure. Finally, challenges are raised to the pediatric community to help with resolving the major issues in the field, namely the variation in classification across sites and the exclusion of some children who have multiple etiologies for their school failure.

Intimacy and emotional illness in the general population.

Ninety married couples in the general population received a structured interview to assess their level of intimacy. The couples also completed self-report questionnaires to assess non-psychotic emotional illness and marital adjustment. High levels of intimacy were associated with martial adjustment. Low ratings of marital intimacy were significantly associated with non-psychotic emotional illness and psychiatric help-seeking. These findings are discussed in relationship to recent studies which explore the role of lack of marital intimacy as a vulnerability factor in the development of non-psychotic emotional illness. Implications for treatment of non-psychotic emotional illness in married individuals is briefly discussed.