Molecular design rules for imparting multiple damping modes in dynamic covalent polymer networks

Imparting multiple, distinct dynamic processes at precise timescales in polymers is a grand challenge in soft materials design with implications for applications including electrolytes, adhesives, tissue engineering, and additive manufacturing. Many competing factors including the polymer architecture, molecular weight, backbone chemistry, and presence of solvent affect the local and global dynamics, and in many cases are interrelated. One approach to imparting distinct dynamic processes is through the incorporation of dynamic bonds with widely varying kinetics of bond exchange. Here, statistically crosslinked polymer networks are synthesized with mixed fast and slow dynamic bonds with four orders of magnitude different exchange kinetics. Oscillatory shear rheology shows that the single component networks (either fast or slow) exhibit a single relaxation peak, while mixing fast and slow crosslinkers in one network produces two peaks in the relaxation spectrum. This is in stark contrast to telechelic networks with the same mixture of dynamic bonds where only one mixed mode is observed, and here we develop the molecular design rules necessary to have each dynamic bond contribute a distinct relaxation mode. By controlling the polymer architecture and difference in the number of dynamic bonds per chain, we have elucidated the role of network architecture on imparting multimodal behavior in dynamic networks. A highly tunable and recyclable material has been developed with control of rubbery plateau modulus (through crosslink density), relaxation peak locations and ratio (through crosslinker selection and molar fractions), and tan δ (through the relationships of the rubbery plateau and relaxation peak locations)

Stress fractures of the upper extremity

INTRODUCTION: The APOSTEL-II trial was a multicenter randomized placebo-controlled trial, assessing the effectiveness of maintenance tocolysis with nifedipine. The trial showed maintenance tocolysis not to have an effect on perinatal outcome. Objective of the current study is to evaluate the effect of a negative trial on the length of hospital admission of women with threatened preterm labor. MATERIALS AND METHODS: We evaluated length of hospital admission of all patients admitted with threatened preterm labor with a gestational age <32 weeks in 8 perinatal centers that participated in the APOSTEL-II trial. We studied only the first admission with threatened preterm labor, readmissions were excluded. We distinguished between the period before, the period during and the period after the trial. In a subgroup analysis, we differentiated for the group of women who delivered and for the group of women who did not deliver during the initial admission. RESULTS: The mean length of hospital admission was 9.3 days before the start of the trial, 8.4 days during the recruitment period and 8.1 days after the trial was completed. The difference in mean length of hospital admission before and during the recruitment period was significantly different (p<001). COMMENTS: The length of hospital admission of women with threatened preterm labor is found to be reduced during the recruitment period of the APOSTEL-II trial. This shows that the conduct of a randomized controlled trial itself has the potential to change daily practice

Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: the MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding)

BACKGROUND: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. METHODS/DESIGN: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women >/= 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. DISCUSSION: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: NTR4197 . Date of registration: October 2(nd) 2013

Amnioinfusion Compared With No Intervention in Women With Second-Trimester Rupture of Membranes A Randomized Controlled Trial

OBJECTIVE: To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes. METHODS: We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a oneto- one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (b error 0.20, two-sided a error 0.05). RESULTS: Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.601.22, P5.39). CONCLUSION: In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion.Research into fetal development and medicin

Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial

BACKGROUND: In women with threatened preterm birth, delay of delivery by 48 h allows antenatal corticosteroids to improve neonatal outcomes. For this reason, tocolytics are often administered for 48 h; however, there is no consensus about which drug results in the best maternal and neonatal outcomes. In the APOSTEL III trial we aimed to compare the effectiveness and safety of the calcium-channel blocker nifedipine and the oxytocin inhibitor atosiban in women with threatened preterm birth. METHODS: We did this multicentre, randomised controlled trial in ten tertiary and nine teaching hospitals in the Netherlands and Belgium. Women with threatened preterm birth (gestational age 25-34 weeks) were randomly assigned (1:1) to either oral nifedipine or intravenous atosiban for 48 h. An independent data manager used a web-based computerised programme to randomly assign women in permuted block sizes of four, with groups stratified by centre. Clinicians, outcome assessors, and women were not masked to treatment group. The primary outcome was a composite of adverse perinatal outcomes, which included perinatal mortality, bronchopulmonary dysplasia, sepsis, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis. Analysis was done in all women and babies with follow-up data. The study is registered at the Dutch Clinical Trial Registry, number NTR2947. FINDINGS: Between July 6, 2011, and July 7, 2014, we randomly assigned 254 women to nifedipine and 256 to atosiban. Primary outcome data were available for 248 women and 297 babies in the nifedipine group and 255 women and 294 babies in the atosiban group. The primary outcome occurred in 42 babies (14%) in the nifedipine group and in 45 (15%) in the atosiban group (relative risk [RR] 0.91, 95% CI 0.61-1.37). 16 (5%) babies died in the nifedipine group and seven (2%) died in the atosiban group (RR 2.20, 95% CI 0.91-5.33); all deaths were deemed unlikely to be related to the study drug. Maternal adverse events did not differ between groups. INTERPRETATION: In women with threatened preterm birth, 48 h of tocolysis with nifedipine or atosiban results in similar perinatal outcomes. Future clinical research should focus on large placebo-controlled trials, powered for perinatal outcomes. FUNDING: ZonMw (the Netherlands Organisation for Health Research and Development)

The impact of fetal gender and ethnicity on the risk of spontaneous preterm delivery in women with symptoms of preterm labor

OBJECTIVE: The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD). METHODS: A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated. RESULTS: Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0)). CONCLUSIONS: The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity

Influence of physical activity on serum IL-6 and IL-10 levels in healthy older men

OBJECTIVE: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor. STUDY DESIGN: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10mm, group 2 CL 10-30mm and positive fFN, group 3 CL 10-30mm and negative fFN, group 4 CL>30mm. RESULTS: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively. CONCLUSION: ACS were prescribed frequently to women with a CL of 10-30mm and a negative fFN test or a CL>30mm. There is room for improvement in the prescription of ACS in these low risk women

Randomized Comparison of Nifedipine and Placebo in Fibronectin-Negative Women with Symptoms of Preterm Labor and a Short Cervix (APOSTEL-I Trial)

Research into fetal development and medicin

[Perinatal policy in cases of extreme prematurity; an investigation into the implementation of the guidelines]

Item does not contain fulltextOBJECTIVE: To determine to what extent the recommendations to actively treat preterm infants with a gestational age of 24 weeks upwards laid down in the guidelines 'Perinatal policy in cases of extreme prematurity' have influenced policy in Dutch perinatal centres in the first year after publication, and what the health outcomes were. DESIGN: Retrospective, descriptive study. METHOD: Our study population included all pregnant women who were admitted to a perinatal centre at 23 5/7 to 26 weeks gestation with a diagnosis of 'threatened preterm labour', and their preterm infants. We collected both obstetric data and data on survival and morbidity of the infants from the medical files. RESULTS: Of a total of 192 preterm infants 185 (96%) were born alive; 92% of these infants were admitted to the neonatal intensive care unit. Survival rates were 43% and 61% at 24 weeks and 25 weeks gestation, respectively. Short-term morbidity (bronchopulmonary dysplasia, retinopathy of the newborn, severe intraventricular haemorrhage, necrotising enterocolitis and persistant ductus arteriosus) occurred in 79% and 71% of the infants born at 24 weeks and 25 weeks gestation, respectively. CONCLUSIONS: The recommendations from these guidelines have been implemented swiftly in Dutch perinatal centres, and survival of extremely preterm infants has increased. This has imposed a considerable burden on the capacity of these centres. Little is yet known about the long-term (up to school-age) health and survival of these infants