Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Inhibition allostérique d'une métallo-beta-lactamase de la famille des VIMs par un nanobody de camélidés.

Metallo-β-lactamase (MβL) enzymes are usually produced by multiresistant Gram-negative bacterial strains and have spread worldwide. An approach based on phage display was employed to select single-domain antibody fragments (VHHs also called Nanobodies) that would inhibit the clinically relevant VIM-4 MβL. Out of more than 50 selected nanobodies, only the NbVIM_38 nanobody inhibited VIM-4. The paratope, inhibition mechanism and epitope of NbVIM_38 nanobody were then characterised. An alanine scan of the NbVIM_38 paratope showed that its binding was driven by hydrophobic amino acids. The inhibitory concentration was in the µM range for all tested β-lactams. In addition, the inhibition was found to follow a mixed hyperbolic profile with a predominantly uncompetitive component. Moreover, substrate inhibition was recorded only after nanobody binding. These kinetic data are indicative of a binding site that is distant from the active site. This finding was confirmed by epitope mapping analysis that was performed using peptides, and which identified two stretches of amino acids in the L6 loop and at the end of the alpha2 helix. Because this binding site is distant from the active site and alters both the substrate binding and catalytic properties of VIM-4, this nanobody can be considered as an allosteric inhibitor.Sélection et caractérisation de Nanobodies inhibiteurs de β-lactamases

Impacts of AKST on development and sustainability goals

The International Assessment of Agricultural Knowledge, Science, and Technology for Development (IAASTD) looks realistically at how we could effectively use agriculture/AKST to help us meet development and sustainability goals. An unprecedented three-year collaborative effort, the IAASTD involved more than 400 authors in 110 countries and cost more than $11 million. It reports on the advances and setbacks of the past fifty years and offers options for the next fifty years. The results of the project are contained in seven reports: a Global Report, five regional Sub-Global Assessments, and a Synthesis Report. The Global Report gives the key findings of the Assessment, and the five Sub-Global Assessments address regional challenges. The volumes present options for action. All of the reports have been extensively peer-reviewed by governments and experts and all have been approved by a panel of participating governments. The Sub-Global Assessments all utilize a similar and consistent framework: examining and reporting on the impacts of AKST on hunger, poverty, nutrition, human health, and environmental/social sustainability. The IAASTD was initiated by the World Bank and the United Nations Food and Agricultural Organization, with support from the World Bank, the World Health Organization, and other sponsors. Its goal is to analyze the potential of agricultural knowledge, science, and technology (AKST) for reducing hunger and poverty, improving rural livelihoods, and working toward environmentally, socially, and economically sustainable development

Impacts of AKST on development and sustainability goals

The International Assessment of Agricultural Knowledge, Science, and Technology for Development (IAASTD) looks realistically at how we could effectively use agriculture/AKST to help us meet development and sustainability goals. An unprecedented three-year collaborative effort, the IAASTD involved more than 400 authors in 110 countries and cost more than $11 million. It reports on the advances and setbacks of the past fifty years and offers options for the next fifty years. The results of the project are contained in seven reports: a Global Report, five regional Sub-Global Assessments, and a Synthesis Report. The Global Report gives the key findings of the Assessment, and the five Sub-Global Assessments address regional challenges. The volumes present options for action. All of the reports have been extensively peer-reviewed by governments and experts and all have been approved by a panel of participating governments. The Sub-Global Assessments all utilize a similar and consistent framework: examining and reporting on the impacts of AKST on hunger, poverty, nutrition, human health, and environmental/social sustainability. The IAASTD was initiated by the World Bank and the United Nations Food and Agricultural Organization, with support from the World Bank, the World Health Organization, and other sponsors. Its goal is to analyze the potential of agricultural knowledge, science, and technology (AKST) for reducing hunger and poverty, improving rural livelihoods, and working toward environmentally, socially, and economically sustainable development

A randomized trial of planned cesarean or vaginal delivery for twin pregnancy

Background: Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy.\ud \ud Methods: We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison.\ud \ud Results: A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the planned-vaginal-delivery group (mean number of days from randomization to delivery, 12.4 vs. 13.3; P = 0.04). There was no significant difference in the composite primary outcome between the planned-cesarean-delivery group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to 1.74; P = 0.49).\ud \ud Conclusion: In twin pregnancy between 32 weeks 0 days and 38 weeks 6 days of gestation, with the first twin in the cephalic presentation, planned cesarean delivery did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery