Prediction of school outcome after preterm birth:a cohort study

Objective To identify if the educational trajectories of preterm infants differ from those of their term peers. Design This work is based on the Avon Longitudinal Study of Parents and Children (ALSPAC). Educational measures were categorised into 10 deciles to allow comparison of measures across time periods. Gestational age was categorised as preterm (23–36 weeks) or term (37–42 weeks). Multilevel mixed-effects linear regression models were derived to examine the trajectories of decile scores across the study period. Gestational group was added as an interaction term to assess if the trajectory between educational measures varied between preterm and term infants. Adjustment for possible confounders was performed. Subjects The final dataset contained information on 12 586 infants born alive at between 23 weeks and 42 weeks of gestation. Main outcome measures UK mandatory educational assessments (SATs) scores throughout educational journal (including final GCSE results at 16 years of age). Results Preterm infants had on average lower Key Stage (KS) scores than term children (−0.46 (−0.84 to −0.07)). However, on average, they gained on their term peers in each progressive measure (0.10 (0.01 to 0.19)), suggesting ‘catch up’ during the first few years at school. Preterm infants appeared to exhibit the increase in decile scores mostly between KS1 and KS2 (p=0.005) and little between KS2 and KS3 (p=0.182) or KS3 and KS4 (p=0.149). Conclusions This work further emphasises the importance of early schooling and environment in these infants and suggests that support, long after the premature birth, may have additional benefits

Working with multidisciplinary or non-academic collaborators as mentors

Mentoring relationships in academia are traditionally constructed as hierarchies, where a supervisor mentors a trainee, or an advisory committee guides a trainee. We propose that all collaborations are mutual mentorship opportunities, where all people involved learn from each other while working towards a common goal. Moreover, researchers and trainees can be mentored or learn from non-academic mentors in different disciplines or sectors. Herein we outline a tutorial on how to break down a research project into stages, and the logistics and value of engaging mentors or collaborators from different sectors and disciplines at each stage, and how multidisciplinary or non-academic collaborators can provide mentoring to support trainee learning and academic success

TreasureDrop – enzyme engineering for applied biocatalysis using microfluidics

Enzymes have established as a new class of catalysts in the field of modern synthetic chemistry. Engineering is arguable the most promising approach to generate desired catalytic activities and its success directly correlates with the library size that can be screened. One of the most powerful technologies enabling the quick and cost-effective testing of millions of enzyme variants is the recently introduced microfluidic droplet-based screening. Interestingly, even though numerous publications highlight its potential, an unambiguous evidence of its ability to provide synthetically relevant biocatalysts still needs to be furnished. We present the engineering of an alcohol dehydrogenase for the challenging enantioselective reduction of a prochiral ketone targeting an important key building block for biologically active compounds. The final aim is not only to obtain an improved variant which allows to perform the selected biotransformation efficiently, but also a comparison of varying evolution paths. Please click Additional Files below to see the full abstract

Raising suspicion of maltreatment from burns:derivation and validation of the BuRN-Tool

Background 10–25% of childhood burns arise from maltreatment. Aim To derive and validate a clinical prediction tool to assist the recognition of suspected maltreatment. Methods Prospectively collected data from 1327 children with burns were analyzed using logistic regression. Regression coefficients for variables associated with ‘referral for child maltreatment investigation’ (112 cases) in multivariable analyses were converted to integers to derive the BuRN-Tool, scoring each child on a continuous scale. A cut-off score for referral was established from receiver operating curve analysis and optimal sensitivity and specificity values. We validated the BuRN-Tool on 787 prospectively collected novel cases. Results Variables associated with referral were: age <5 years, known to social care, concerning explanation, full thickness burn, uncommon body location, bilateral pattern and supervision concern. We established 3 as cut-off score, resulting in a sensitivity and specificity for scalds of 87.5% (95% CI:61.7–98.4) and 81.5% (95% CI:77.1–85.4) respectively and for non-scalds sensitivity was 82.4% (95%CI:65.5–93.2) and specificity 78.7% (95% CI:73.9–82.9) when applied to validation data. Area under the curve was 0.87 (95% CI:0.83–0.90) for scalds and 0.85 (95% CI:0.81–0.88) for non-scalds. Conclusion The BuRN-Tool is a potential adjunct to clinical decision-making, predicting which children warrant investigation for child maltreatment. The score is simple and easy to complete in an emergency department setting

Embedded Weapons-Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats

Continuing concern regarding the potential health and environmental effects of depleted uranium and lead has resulted in many countries adding tungsten alloy (WA)-based munitions to their battlefield arsenals as replacements for these metals. Because the alloys used in many munitions are relatively recent additions to the list of militarily relevant metals, very little is known about the health effects of these metals after internalization as embedded shrapnel. Previous work in this laboratory developed a rodent model system that mimicked shrapnel loads seen in wounded personnel from the 1991 Persian Gulf War. In the present study, we used that system and male F344 rats, implanted intramuscularly with pellets (1 mm × 2 mm cylinders) of weapons-grade WA, to simulate shrapnel wounds. Rats were implanted with 4 (low dose) or 20 pellets (high dose) of WA. Tantalum (20 pellets) and nickel (20 pellets) served as negative and positive controls, respectively. The high-dose WA-implanted rats (n = 46) developed extremely aggressive tumors surrounding the pellets within 4–5 months after implantation. The low-dose WA-implanted rats (n = 46) and nickel-implanted rats (n = 36) also developed tumors surrounding the pellets but at a slower rate. Rats implanted with tantalum (n = 46), an inert control metal, did not develop tumors. Tumor yield was 100% in both the low- and high-dose WA groups. The tumors, characterized as high-grade pleomorphic rhabdomyosarcomas by histopathology and immunohistochemical examination, rapidly metastasized to the lung and necessitated euthanasia of the animal. Significant hematologic changes, indicative of polycythemia, were also observed in the high-dose WA-implanted rats. These changes were apparent as early as 1 month postimplantation in the high-dose WA rats, well before any overt signs of tumor development. These results point out the need for further studies investigating the health effects of tungsten and tungsten-based alloys

Le Forum, Vol. 40 No. 3

https://digitalcommons.library.umaine.edu/francoamericain_forum/1088/thumbnail.jp

Engineering the protein dynamics of an ancestral luciferase.

Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein AncHLD-RLuc which catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of AncHLD-RLuc challenged the scaffold dynamics. Screening for both activities reveals InDel mutations localized in three distinct regions that lead to altered protein dynamics (based on crystallographic B-factors, hydrogen exchange, and molecular dynamics simulations). An anisotropic network model highlights the importance of the conformational flexibility of a loop-helix fragment of Renilla luciferases for ligand binding. Transplantation of this dynamic fragment leads to lower product inhibition and highly stable glow-type bioluminescence. The success of our approach suggests that a strategy comprising (i) constructing a stable and evolvable template, (ii) mapping functional regions by backbone mutagenesis, and (iii) transplantation of dynamic features, can lead to functionally innovative proteins

Circulating estradiol and its biologically active metabolites in endometriosis and in relation to pain symptoms

ObjectivesEndometriosis (EM) is an estrogen-dominant inflammatory disease linked to infertility that affects women of reproductive age. EM lesions respond to hormonal signals that regulate uterine tissue growth and trigger inflammation and pain. The objective of this study was to evaluate whether estradiol (E2) and its biologically active metabolites are differentially associated with EM given their estrogenic and non-estrogenic actions including proliferative and inflammatory properties.DesignWe performed a retrospective study of 209 EM cases and 115 women without EM.MethodsPain-related outcomes were assessed using surveys with validated scales. Preoperative serum levels of estradiol (E2) and estrone (E1), their 2-, 4- and 16- hydroxylated (OH) and methylated (MeO) derivatives (n=16) were measured by mass spectrometry. We evaluated the associations between estrogen levels and EM anatomic sites, surgical stage, risk of EM, and symptoms reported by women. Spearman correlations established the relationships between circulating steroids.ResultsOf the sixteen estrogens profiled, eleven were detected above quantification limits in most individuals. Steroids were positively correlated, except 2-hydroxy 3MeO-E1 (2OH-3MeO-E1). Higher 2OH-3MeO-E1 was linked to an increased risk of EM (Odd ratio (OR)=1.91 (95%CI 1.09-3.34); P=0.025). Ovarian EM cases displayed enhanced 2-hydroxylation with higher 2MeO-E1 and 2OH-E1 levels (P&lt; 0.009). Abdominal, pelvic and back pain symptoms were also linked to higher 2OH-3MeO-E1 levels (OR=1.86; 95%CI 1.06-3.27; P=0.032).ConclusionsThe 2-hydroxylation pathway emerges as an unfavorable feature of EM, and is associated with ovarian EM and pain related outcomes

Household Tobacco Smoke and Admission Weight Predict Severe Bronchiolitis in Infants Independent of Deprivation: Prospective Cohort Study

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors

Engineering the protein dynamics of an ancestral luciferase

Abstract: Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein AncHLD-RLuc which catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of AncHLD-RLuc challenged the scaffold dynamics. Screening for both activities reveals InDel mutations localized in three distinct regions that lead to altered protein dynamics (based on crystallographic B-factors, hydrogen exchange, and molecular dynamics simulations). An anisotropic network model highlights the importance of the conformational flexibility of a loop-helix fragment of Renilla luciferases for ligand binding. Transplantation of this dynamic fragment leads to lower product inhibition and highly stable glow-type bioluminescence. The success of our approach suggests that a strategy comprising (i) constructing a stable and evolvable template, (ii) mapping functional regions by backbone mutagenesis, and (iii) transplantation of dynamic features, can lead to functionally innovative proteins