Achieving accurate estimates of fetal gestational age and personalised predictions of fetal growth based on data from an international prospective cohort study: A population-based machine learning study

Background: Preterm birth is a major global health challenge, the leading cause of death in children under 5 years of age, and a key measure of a population\u27s general health and nutritional status. Current clinical methods of estimating fetal gestational age are often inaccurate. For example, between 20 and 30 weeks of gestation, the width of the 95% prediction interval around the actual gestational age is estimated to be 18-36 days, even when the best ultrasound estimates are used. The aims of this study are to improve estimates of fetal gestational age and provide personalised predictions of future growth.Methods: Using ultrasound-derived, fetal biometric data, we developed a machine learning approach to accurately estimate gestational age. The accuracy of the method is determined by reference to exactly known facts pertaining to each fetus-specifically, intervals between ultrasound visits-rather than the date of the mother\u27s last menstrual period. The data stem from a sample of healthy, well-nourished participants in a large, multicentre, population-based study, the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st). The generalisability of the algorithm is shown with data from a different and more heterogeneous population (INTERBIO-21st Fetal Study).Findings: In the context of two large datasets, we estimated gestational age between 20 and 30 weeks of gestation with 95% confidence to within 3 days, using measurements made in a 10-week window spanning the second and third trimesters. Fetal gestational age can thus be estimated in the 20-30 weeks gestational age window with a prediction interval 3-5 times better than with any previous algorithm. This will enable improved management of individual pregnancies. 6-week forecasts of the growth trajectory for a given fetus are accurate to within 7 days. This will help identify at-risk fetuses more accurately than currently possible. At population level, the higher accuracy is expected to improve fetal growth charts and population health assessments.Interpretation: Machine learning can circumvent long-standing limitations in determining fetal gestational age and future growth trajectory, without recourse to often inaccurately known information, such as the date of the mother\u27s last menstrual period. Using this algorithm in clinical practice could facilitate the management of individual pregnancies and improve population-level health. Upon publication of this study, the algorithm for gestational age estimates will be provided for research purposes free of charge via a web portal.Funding: Bill & Melinda Gates Foundation, Office of Science (US Department of Energy), US National Science Foundation, and National Institute for Health Research Oxford Biomedical Research Centre

A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies

The presence of serum bactericidal antibodies is a proven correlate of protection against systemic infection with the important human pathogen Neisseria meningitidis. We have identified three serogroup C N. meningitidis (MenC) isolates recovered from patients with invasive meningococcal disease that resist killing by bactericidal antibodies induced by the MenC conjugate vaccine. None of the patients had received the vaccine, which has been successfully introduced in countries in North America and Europe. The increased resistance was not caused by changes either in lipopolysaccharide sialylation or acetylation of the α2-9–linked polysialic acid capsule. Instead, the resistance of the isolates resulted from the presence of an insertion sequence, IS1301, in the intergenic region (IGR) between the sia and ctr operons, which are necessary for capsule biosynthesis and export, respectively. The insertion sequence led to an increase in the transcript levels of surrounding genes and the amount of capsule expressed by the strains. The increased amount of capsule was associated with down-regulation of the alternative pathway of complement activation, providing a generic mechanism by which the bacterium protects itself against bactericidal antibodies. The strains with IS1301 in the IGR avoided complement-mediated lysis in the presence of bactericidal antibodies directed at the outer membrane protein, PorA, or raised against whole cells

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

The asymmetric and catalytic Michael reaction between α-nitroesters and nitroalkenes has been studied in the presence of two bifunctional catalysts both containing the same absolute chirality at the carbon backbone. The reaction performed in similar conditions allows us to control the syn or anti selectivity of the Michael adduct obtaining good yields and high enantiocontrol in all cases

Binding of C3 (A and C) and MAC (B and D) to bacteria detected by FACS analysis after incubation in immune human serum pooled from 10 donors

Results are shown as the MFI (calculated as geometric mean multiplied by the percentage of gated cells), and the error bars show the SEM. In B and D, strains were incubated with serum in the presence of magnesium and EGTA to block the CP and LP (-CP/LP). Error bars show the SEM of assays performed in triplicate. There was significantly less binding of complement factors to R3 and S3∷R compared with S3. P < 0.01 in all assays with the Student's test.<p><b>Copyright information:</b></p><p>Taken from "A generic mechanism in for enhanced resistance against bactericidal antibodies"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1423-1434.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413038.</p><p></p

Capsular material was detected around the surface of the sensitive strain S3 (A and B, arrows) but not the corresponding mutant (C and D)

Strains R3 and S3∷R (E and F; and G and H, respectively) expressed larger amounts of capsule, which formed large extracellular aggregates in places. Bars, 400 nm.<p><b>Copyright information:</b></p><p>Taken from "A generic mechanism in for enhanced resistance against bactericidal antibodies"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1423-1434.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413038.</p><p></p

(A) SBA titers using sera from eight vaccinees against the R strains and the control strain, C11

All sera had SBA titers of <p><b>Copyright information:</b></p><p>Taken from "A generic mechanism in for enhanced resistance against bactericidal antibodies"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1423-1434.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413038.</p><p></p

No significant difference was identified between the capsules from strains S3 (A) and R3 (B)

The asterisk denotes the internal standard (acetone), and the prominent and distorted peaks at ∼4.8 parts per million (ppm) in both spectra are caused by partially deuterated water.<p><b>Copyright information:</b></p><p>Taken from "A generic mechanism in for enhanced resistance against bactericidal antibodies"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1423-1434.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413038.</p><p></p

The relative amounts of (A) and (B) transcripts from S3, R3, and S3∷R measured by qrtRT-PCR

Error bars show the SEM of assays performed in triplicate. P < 0.005 for differences in and mRNA levels in R3 and S3∷R versus S3 using the Student's test. (C) Western blot analysis of SiaA and RecA in whole-cell lysates. The strains are indicated above each lane, and the sizes of the proteins (in kD) are shown. (D) Expression of the polysialic capsule detected by FACS. Bacteria were incubated with polyclonal antisera raised against the MCC vaccine (black, capsule-negative strain R3Δ; blue, S3; red, S3∷R; purple, R3). (E) Relative amount of capsule detected by FACS. Results are shown as the MFI (calculated as the geometric mean multiplied by the percentage of positive cells). Error bars show the SEM. P < 0.005 for both strains with increased resistance versus S3 using the Student's test.<p><b>Copyright information:</b></p><p>Taken from "A generic mechanism in for enhanced resistance against bactericidal antibodies"</p><p></p><p>The Journal of Experimental Medicine 2008;205(6):1423-1434.</p><p>Published online 9 Jun 2008</p><p>PMCID:PMC2413038.</p><p></p