SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital.

BACKGROUND: Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection. AIMS: To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia. METHODS: In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT-PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT-PCR/antigen test (<3 months, 3-6 months, >6 months). RESULTS: We included 1021 workers (80% women, median age 34 years (interquartile range 28-42), 73% medical personnel, 23% with previous positive RT-PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6-37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT-PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3-6 months) and 48% (>6 months). In participants with a previous negative RT-PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3-6 months) and 29% (>6 months). CONCLUSIONS: High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT-PCR/antigen status and time elapsed since the diagnostic test.

Clinical phenotypes for risk stratification in small-for-gestational-age fetuses.

OBJECTIVE: To evaluate whether clinical phenotypes of small-for-gestational-age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision-making. METHODS: This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two-step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi-square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age. RESULTS: The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH-21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three-times higher risk of perinatal mortality compared with non-SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17-136.12)) and second- or third-trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23-80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27-72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62-35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21-10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate-for-gestational-age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06-2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non-SGA cases with the same condition (OR, 24.40 (95% CI, 1.31-453.91)). CONCLUSIONS: We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision-making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Could pulmonary low-dose radiation therapy be an alternative treatment for patients with COVID-19 pneumonia? Preliminary results of a multicenter SEOR-GICOR nonrandomized prospective trial (IPACOVID trial).

PURPOSE: To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO2) to fractional inspired oxygen (FiO2) ratio of at least 20% at 24 h with respect to the preirradiation value. RESULTS: Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X­ray. All patients received dexamethasone treatment. Mean SpO2 pretreatment value was 94.28% and the SpO2/FiO2 ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. CONCLUSIONS: LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Fetal cerebellar growth and Sylvian fissure maturation: international standards from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. RESULTS: Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-diameter and Sylvian-fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation, with complete overlap of the mean gestational age and 95% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. CONCLUSION: We present, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Clinical impact of Doppler reference charts on management of small-for-gestational-age fetuses: need for standardization.

OBJECTIVE: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR). METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management. RESULTS: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol. CONCLUSIONS: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

International standards for fetal brain structures based on serial ultrasound measurements from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured using ultrasound, in healthy, well-nourished women at low risk of impaired fetal growth and poor perinatal outcome, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicenter, longitudinal study. The sample analyzed was selected randomly from the overall FGLS population, ensuring an equal distribution among the eight diverse participating sites and of three-dimensional (3D) ultrasound volumes across pregnancy (range: 15-36 weeks' gestation). We measured, in planes reconstructed from 3D ultrasound volumes of the fetal head at different timepoints in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle, atrium of the posterior horn of the lateral ventricle (PV) and cisterna magna (CM). Fractional polynomials were used to construct the standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were selected at random. After exclusions, 3D ultrasound volumes from 442 fetuses born without a congenital malformation were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures, except the PV, showed increasing size with gestational age, and the size of the POF, SF, PV and CM showed increasing variability. The 3rd , 5th , 50th , 95th and 97th smoothed centiles are presented. The 5th centiles for the POF and SF were 3.1 mm and 4.7 mm at 22 weeks' gestation and 4.6 mm and 9.9 mm at 32 weeks, respectively. The 95th centiles for the PV and CM were 8.5 mm and 7.5 mm at 22 weeks and 8.6 mm and 9.5 mm at 32 weeks, respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcome. We recommend these as international standards for the assessment of measurements obtained using ultrasound from fetal brain structures. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

First Results on Dark Matter Annual Modulation from the ANAIS-112 Experiment.

ANAIS is a direct detection dark matter experiment aiming at the testing of the DAMA/LIBRA annual modulation result, which, for about two decades, has neither been confirmed nor ruled out by any other experiment in a model independent way. ANAIS-112, consisting of 112.5 kg of sodium iodide crystals, has been taking data at the Canfranc Underground Laboratory, Spain, since August 2017. This Letter presents the annual modulation analysis of 1.5 years of data, amounting to 157.55 kg yr. We focus on the model independent analysis searching for modulation and the validation of our sensitivity prospects. ANAIS-112 data are consistent with the null hypothesis (p values of 0.67 and 0.18 for [2-6] and [1-6] keV energy regions, respectively). The best fits for the modulation hypothesis are consistent with the absence of modulation (S_{m}=-0.0044±0.0058 cpd/kg/keV and -0.0015±0.0063 cpd/kg/keV, respectively). They are in agreement with our estimated sensitivity for the accumulated exposure, which supports our projected goal of reaching a 3σ sensitivity to the DAMA/LIBRA result in five years of data taking.

Reference ranges for Doppler indices of umbilical and fetal middle cerebral arteries and cerebroplacental ratio: systematic review.

OBJECTIVE: To assess studies reporting reference ranges for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR), using a set of predefined methodological quality criteria for study design, statistical analysis and reporting methods. METHODS: This was a systematic review of observational studies in which the primary aim was to create reference ranges for UA and MCA Doppler indices and CPR in fetuses of singleton gestations. A search for relevant articles was performed in MEDLINE, EMBASE, CINAHL, Web of Science (from inception to 31 December 2016) and references of the retrieved articles. Two authors independently selected studies, assessed the risk of bias and extracted the data. Studies were scored against a predefined set of independently agreed methodological criteria and an overall quality score was assigned to each study. Linear multiple regression analysis assessing the association between quality scores and study characteristics was performed. RESULTS: Thirty-eight studies met the inclusion criteria. The highest potential for bias was noted in the following fields: 'ultrasound quality control measures', in which only two studies demonstrated a comprehensive quality-control strategy; 'number of measurements taken for each Doppler variable', which was apparent in only three studies; 'sonographer experience', in which no study on CPR reported clearly the experience or training of the sonographers, while only three studies on UA Doppler and four on MCA Doppler did; and 'blinding of measurements', in which only one study, on UA Doppler, reported that sonographers were blinded to the measurement recorded during the examination. Sample size estimations were present in only seven studies. No predictors of quality were found on multiple regression analysis. Reference ranges varied significantly with important clinical implications for what is considered normal or abnormal, even when restricting the analysis to the highest scoring studies. CONCLUSIONS: There is considerable methodological heterogeneity in studies reporting reference ranges for UA and MCA Doppler indices and CPR, and the resulting references have important implications for clinical practice. There is a need for the standardization of methodologies for Doppler velocimetry and for the development of reference standards, which can be correctly interpreted and applied in clinical practice. We propose a set of recommendations for this purpose. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Intervalos de referencia para los índices Doppler de la arterias umbilical y cerebral media del feto y la relación cerebroplacentaria: una revisión sistemática OBJETIVO: Evaluar los estudios que informan sobre intervalos de referencia para los índices Doppler y la relación cerebroplacentaria (RCP) de la arteria umbilical (AU) y la arteria cerebral media (ACM) del feto, mediante un conjunto de criterios de calidad metodológica predefinidos para el diseño del estudio, el análisis estadístico y los métodos de notificación. MÉTODOS: Esta fue una revisión sistemática de estudios observacionales en los que el objetivo principal fue crear intervalos de referencia para los índices Doppler de la AU y la ACM y la RCP de fetos de gestaciones con feto único. Se realizó una búsqueda de artículos relevantes en MEDLINE, EMBASE, CINAHL, Web of Science (desde el inicio hasta el 31 de diciembre de 2016) y en las referencias de los artículos recuperados. Dos autores, de forma independiente, seleccionaron los estudios, evaluaron el riesgo de sesgo y extrajeron los datos. Los estudios se calificaron según un conjunto predefinido de criterios metodológicos acordados de forma independiente y se asignó una puntuación de calidad global a cada estudio. Se realizó un análisis de regresión múltiple lineal para evaluar la asociación entre las puntuaciones de calidad y las características del estudio. RESULTADOS: Un total de 38 estudios cumplieron los criterios de inclusión. El mayor potencial de sesgo se observó en los siguientes casos: 'medidas de control de calidad del ultrasonido', donde sólo dos estudios demostraron una estrategia integral de control de calidad; 'número de mediciones tomadas para cada variable Doppler', que solo fue aparente en tres estudios; 'experiencia del ecografista', puesto que ningún estudio sobre la RCP informó claramente sobre la experiencia o la formación de los ecografistas, y tan solo lo hicieron tres estudios sobre el Doppler de la AU y cuatro sobre el Doppler de la ACM; y 'mediciones a ciegas', donde tan sólo un estudio sobre el Doppler de la AU comunicó que los ecografistas no tuvieron acceso a la medición registrada durante el estudio. Las estimaciones del tamaño de la muestra sólo se comunicaron en siete estudios. No se encontraron predictores de calidad en el análisis de regresión múltiple. Los intervalos de referencia variaron significativamente con implicaciones clínicas importantes para lo que se considera normal o anómalo, incluso cuando se restringió el análisis a los estudios con mayor puntuación. CONCLUSIONES: Existe una heterogeneidad metodológica considerable en los estudios que informan sobre los intervalos de referencia para los índices Doppler de la AU y la ACM y la RCP, y las referencias resultantes tienen implicaciones importantes para la práctica clínica. Es necesario estandarizar las metodologías de la velocimetría Doppler y desarrollar estándares de referencia que puedan ser interpretados y aplicados correctamente en la práctica clínica. Se propone una serie de recomendaciones para este fin.

Tracking the origin and dispersal of the Asian chestnut gall wasp Dryocosmus kuriphilus Yasumatsu (Hymenoptera, Cynipidae) in Europe with molecular markers.

The Asian chestnut gall wasp, Dryocosmus kuriphilus, is an invasive pest causing significant damage to chestnut trees (Castanea spp., Fagaceae). Originating from China, it has recently invaded a wide range of regions in Europe and North America. Understanding the population genetic structure of important invasive pests is very useful for improving the knowledge concerning routes of expansion and colonizing capacity. Despite its economic importance, limited attention has been given to D. kuriphilus origin and spread, or to its genetic structure. In this study, D. kuriphilus populations sampled in eight European countries were screened using both mitochondrial (cytochrome c oxidase subunit 1; COI) and nuclear (internal transcribed spacer 2; ITS2) sequences, and Amplified Fragment Length Polymorphism (AFLP) markers. The molecular markers COI and ITS2 highlighted the presence of a single haplotype in all the studied populations. The recorded mitochondrial haplotype was identical to one of the most widespread haplotypes occurring in the native area (China). AFLP results indicated that D. kuriphilus individuals belong to two genetically distinct clusters without any further geographic clustering. These results suggest that D. kuriphilus populations in Europe could be the result of a single introduction of a Chinese founder population characterized by two genetically distinct lineages that subsequently spread rapidly across Europe. However, the possibility that populations originated from multiple introductions of the same Chinese mitochondrial haplotype cannot be excluded. The reported results provide useful information concerning this invasive species, potentially facilitating integrated pest management.

Protein surface roughness accounts for binding free energy of Plasmepsin II-ligand complexes.

The calculation of absolute binding affinities for protein-inhibitor complexes remains as one of the main challenges in computational structure-based ligand design. The present work explored the calculations of surface fractal dimension (as a measure of surface roughness) and the relationship with experimental binding free energies of Plasmepsin II complexes. Plasmepsin II is an attractive target for novel therapeutic compounds to treat malaria. However, the structural flexibility of this enzyme is a drawback when searching for specific inhibitors. Concerning that, we performed separate explicitly solvated molecular dynamics simulations using the available high-resolution crystal structures of different Plasmepsin II complexes. Molecular dynamics simulations allowed a better approximation to systems dynamics and, therefore, a more reliable estimation of surface roughness. This constitutes a novel approximation in order to obtain more realistic values of fractal dimension, because previous works considered only x-ray structures. Binding site fractal dimension was calculated considering the ensemble of structures generated at different simulation times. A linear relationship between binding site fractal dimension and experimental binding free energies of the complexes was observed within 20 ns. Previous studies of the subject did not uncover this relationship. Regression model, coined FD model, was built to estimate binding free energies from binding site fractal dimension values. Leave-one-out cross-validation showed that our model reproduced accurately the absolute binding free energies for our training set (R2  = 0.76; <|error|> =0.55 kcal/mol; SDerror  = 0.19 kcal/mol). The fact that such a simple model may be applied raises some questions that are addressed in the article.

The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH-21st Project.

OBJECTIVES: To identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well-dated pregnancies and access to antenatal care. DESIGN: Population-based, prospective, observational study. SETTING: Eight international urban populations. POPULATION: Pregnant women and their babies enrolled in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. METHODS: Cox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies. MAIN OUTCOME MEASURES: Antepartum stillbirth was defined as any fetal death after 16 weeks' gestation before the onset of labour. RESULTS: Of 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio-economic status, hazard ratio (HR): 1.6 (95% CI, 1.2-2.1); single marital status, HR 2.0 (95% CI, 1.4-2.8); age ≥40 years, HR 2.2 (95% CI, 1.4-3.7); essential hypertension, HR 4.0 (95% CI, 2.7-5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0-9.1); pre-eclampsia, HR 1.6 (95% CI, 1.1-3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0-5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5-4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4-6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6-7.0). The population-attributable risk of antepartum death associated with small-for-gestational-age neonates diagnosed at birth was 11%. CONCLUSIONS: Antepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth. TWEETABLE ABSTRACT: International stillbirth study finds individual risks poor predictors of death but combinations promising.

Predictive accuracy of cerebroplacental ratio for adverse perinatal and neurodevelopmental outcomes in suspected fetal growth restriction: systematic review and meta-analysis.

OBJECTIVE: The cerebroplacental ratio (CPR) has been proposed for the routine surveillance of pregnancies with suspected fetal growth restriction (FGR), but the predictive performance of this test is unclear. The aim of this study was to determine the accuracy of CPR for predicting adverse perinatal and neurodevelopmental outcomes in suspected FGR. METHODS: PubMed, EMBASE, CINAHL and Lilacs were searched from inception to 31 July 2017 for cohort or cross-sectional studies reporting on the accuracy of CPR for predicting adverse perinatal and/or neurodevelopmental outcomes in singleton pregnancies with FGR suspected antenatally based on sonographic parameters. Summary receiver-operating characteristics (ROC) curves, pooled sensitivities and specificities, and summary likelihood ratios (LRs) were generated. RESULTS: Twenty-two studies (including 4301 women) met the inclusion criteria. Summary ROC curves showed that the best predictive accuracy of CPR was for perinatal death and the worst was for neonatal acidosis, with areas under the summary ROC curves of 0.83 and 0.57, respectively. The predictive accuracy of CPR was moderate to high for perinatal death (pooled sensitivity and specificity of 93% and 76%, respectively, and summary positive and negative LRs of 3.9 and 0.09, respectively) and low for composite of adverse perinatal outcomes, Cesarean section for non-reassuring fetal status, 5-min Apgar score < 7, admission to the neonatal intensive care unit, neonatal acidosis and neonatal morbidity, with summary positive and negative LRs ranging from 1.1 to 2.5 and 0.3 to 0.9, respectively. An abnormal CPR result had moderate accuracy for predicting small-for-gestational age at birth (summary positive LR of 7.4). CPR had a higher predictive accuracy in pregnancies with suspected early-onset FGR. No study provided data for assessing the predictive accuracy of CPR for adverse neurodevelopmental outcome. CONCLUSION: CPR appears to be useful in predicting perinatal death in pregnancies with suspected FGR. Nevertheless, before incorporating CPR into the routine clinical management of suspected FGR, randomized controlled trials should assess whether the use of CPR reduces perinatal death or other adverse perinatal outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Impact on Morbidity, Mortality, and Length of Stay of Hospital-Acquired Infections by Resistant Microorganisms.

BACKGROUND: Infections by multidrug-resistant organisms (MDROs) are a global threat and are particularly common in hospitals. This study was performed to assess the impact of hospital-acquired infections caused by MDROs on morbidity, mortality, and length of hospital stay. METHODS: This was a retrospective cohort study. A sample of adults aged ≥18 years with a respiratory, urinary, bloodstream, or surgical site infection caused by a multidrug-resistant (cases) or -sensitive (controls) microorganism was selected. Measurements included hospital mortality from all causes (total and 30 days after infection), length of stay (LOS), and 5 indicators of morbidity: intensive care or surgery admissions, number of diagnostic tests after infection, and hospital readmissions or visits to the emergency department within 30 days of discharge. RESULTS: The sample was composed of 324 cases and 676 control patients. Risk of hospital mortality from all causes (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.25-2.32) and 30 day-mortality after infection (HR, 1.77; 95% CI, 1.29-2.44) were higher in patients with an MDRO infection. Probability of readmission was also higher (odds ratio [OR], 2.17; 95% CI, 1.36-3.46) in the case group. Emergency department visits were only significantly higher in methicillin-resistant Staphylococcus aureus (OR, 2.80; 95% CI, 1.65-4.74) and in Escherichia coli-resistant infections (OR, 2.28; 95% CI, 1.32-3.96). Infections by MDRO were not associated with any other outcome. CONCLUSIONS: Hospital infections caused by MDROs increase mortality, readmissions, and in some cases, visits to the emergency department compared with those produced by susceptible strains. They do not appear to influence LOS nor the need for hospital admission, intensive care, surgery, or diagnostic tests.

A pathway-based association study reveals variants from Wnt signalling genes contributing to asthma susceptibility.

BACKGROUND: Genetic susceptibility to asthma is currently linked to a handful of genes which have a limited ability to predict the overall disease risk, suggesting the existence of many other genes involved in disease development. Accumulated evidence from association studies in genes related by biological pathways could reveal novel asthma genes. OBJECTIVE: To reveal novel asthma susceptibility genes by means of a pathway-based association study. METHODS: Based on summary data from a previous a genomewide association study (GWAS) of asthma, we first identified significant biological pathways using a gene-set enrichment analysis. We then mapped all tested single nucleotide polymorphisms (SNPs) on the genes contributing to significant pathways and prioritized those with a disproportionate number of nominal significant associations for further studies. For those prioritized genes, association studies were performed for selected SNPs in independent case-control samples (n = 1765) using logistic regression models, and results were meta-analysed with those from the GWAS. RESULTS: Two biological processes were significantly enriched: the cytokine-cytokine receptor interaction (P = 0.002) and the Wnt signalling (P = 0.012). From the 417 genes interacting in these two pathways, 10 showed an excess of nominal associations, including a known asthma susceptibility locus (encoding SMAD family member 3) and other novel candidate genes. From the latter, association studies of 14 selected SNPs evidenced replication in a locus near the frizzled class receptor 6 (FZD6) gene (P = 9.90 × 10-4 ), which had a consistent direction of effects with the GWAS findings (meta-analysed odds ratio = 1.49; P = 5.87 × 10-6 ) and was in high linkage disequilibrium with expression quantitative trait loci in lung tissues. CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed the importance of two biological pathways in asthma pathogenesis and identified a novel susceptibility locus near Wnt signalling genes.

International estimated fetal weight standards of the INTERGROWTH-21st Project.

OBJECTIVE: Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH-21st Fetal Growth Standards that are available for use worldwide. METHODS: Women with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study (FGLS) and INTERBIO-21st Fetal Study (FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9-14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference (HC), biparietal diameter, occipitofrontal diameter, abdominal circumference (AC) and femur length (FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models. RESULTS: Of the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0-14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log(EFW) = 5.084820 - 54.06633 × (AC/100)3 - 95.80076 × (AC/100)3 × log(AC/100) + 3.136370 × (HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis-fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data (n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at < 37 weeks' gestation, the EFW centiles were, as expected, higher than those of babies born preterm. Comparing EFW cross-sectional values with the INTERGROWTH-21st Preterm Postnatal Growth Standards confirmed that preterm postnatal growth is a different biological process from intrauterine growth. CONCLUSIONS: We provide an assessment of EFW, as an adjunct to routine ultrasound biometry, from 22 to 40 weeks' gestation. However, we strongly encourage clinicians to evaluate fetal growth using separate biometric measures such as HC and AC, as well as EFW, to avoid the minimalist approach of focusing on a single value. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Brassica aphid (Hemiptera: Aphididae) populations are conditioned by climatic variables and parasitism level: a study case of Triângulo Mineiro, Brazil.

Cosmopolitan pests such as Brevicoryne brassicae, Lipaphis pseudobrassicae, and Myzus persicae (Aphididae) cause significant damage to Brassicaceae crops. Assessment of the important biotic and abiotic factors that regulate these pests is an essential step in the development of effective Integrated Pest Management programs for these aphids. This study evaluated the influence of leaf position, precipitation, temperature, and parasitism on populations of L. pseudobrassicae, M. persicae, and B. brassicae in collard greens fields in the Triângulo Mineiro region (Minas Gerais state), Brazil. Similar numbers of B. brassicae were found on all parts of the collard green plants, whereas M. persicae and L. pseudobrassicae were found in greatest numbers on the middle and lower parts of the plant. While temperature and precipitation were positively related to aphid population size, their effects were not accumulative, as indicated by a negative interaction term. Although Diaeretiella rapae was the main parasitoid of these aphids, hyperparasitism was dominant; the main hyperparasitoid species recovered from plant samples was Alloxysta fuscicornis. Parasitoids seem to have similar distributions on plants as their hosts. These results may help predict aphid outbreaks and gives clues for specific intra-plant locations when searching for and monitoring aphid populations.

Ultrasound-based gestational-age estimation in late pregnancy.

OBJECTIVE: Accurate gestational-age (GA) estimation, preferably by ultrasound measurement of fetal crown-rump length before 14 weeks' gestation, is an important component of high-quality antenatal care. The objective of this study was to determine how GA can best be estimated by fetal ultrasound for women who present for the first time late in pregnancy with uncertain or unknown menstrual dates. METHODS: INTERGROWTH-21st was a large, prospective, multicenter, population-based project performed in eight geographically defined urban populations. One of its principal components, the Fetal Growth Longitudinal Study, aimed to develop international fetal growth standards. Each participant had their certain menstrual dates confirmed by first-trimester ultrasound examination. Fetal head circumference (HC), biparietal diameter (BPD), occipitofrontal diameter (OFD), abdominal circumference (AC) and femur length (FL) were measured every 5 weeks from 14 weeks' gestation until delivery. For each participant, a single, randomly selected ultrasound examination was used to explore all candidate biometric variables and permutations to build models to predict GA. Regression equations were ranked based upon minimization of the mean prediction error, goodness of fit and model complexity. An automated machine learning algorithm, the Genetic Algorithm, was adapted to evaluate > 64 000 potential polynomial equations as predictors. RESULTS: Of the 4607 eligible women, 4321 (94%) had a pregnancy without major complications and delivered a live singleton without congenital malformations. After other exclusions (missing measurements in GA window and outliers), the final sample comprised 4229 women. Two skeletal measures, HC and FL, produced the best GA prediction, given by the equation loge (GA) = 0.03243 × (loge (HC))2 + 0.001644 × FL × loge (HC) + 3.813. When FL was not available, the best equation based on HC alone was loge (GA) = 0.05970 × (loge (HC))2 + 0.000000006409 × (HC)3 + 3.3258. The estimated uncertainty of GA prediction (half width 95% interval) was 6-7 days at 14 weeks' gestation, 12-14 days at 26 weeks' gestation and > 14 days in the third trimester. The addition of FL to the HC model led to improved prediction intervals compared with using HC alone, but no further improvement in prediction was afforded by adding AC, BPD or OFD. Equations that included other measurements (BPD, OFD and AC) did not perform better. CONCLUSIONS: Among women initiating antenatal care late in pregnancy, a single set of ultrasound measurements combining HC and FL in the second trimester can be used to estimate GA with reasonable accuracy. We recommend this tool for underserved populations but considerable efforts should be implemented to improve early initiation of antenatal care worldwide. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Rehabilitation of hemineglect of the left arm using movement detection bracelets activating a visual and acoustic alarm.

BACKGROUND: Hemineglect is frequent after right hemisphere stroke and prevents functional independence, but effective rehabilitation interventions are lacking. Our objective was to determine if a visual-acoustic alarm in the hemineglect arm activated by a certain discrepancy in movement of both hands can enhance neglect arm use in five tasks of daily living. METHODS: In this pre-post intervention study 9 stroke patients with residual hemineglect of the arm were trained for 7 days in five bimanual tasks of daily living: carrying a tray, button fastening, cutting food with knife and fork, washing the face with both hands and arm sway while walking. This was done through motion sensors mounted in bracelets on both wrists that compared movement between them. When the neglect-hand movement was less than a limit established by two fuzzy logic based classifiers, a visual-acoustic alarm in the neglect-hand bracelet was activated to encourage its use in the task. RESULTS: Both motion and function of the neglect hand improved during the seven days of training when visual-acoustic alarms were active but a worsening to baseline values occurred on day 8 and day 30 when alarms where switched off. Improvement was limited to vision-dependent tasks. CONCLUSIONS: Neglect-hand improvement with this approach is limited to bimanual activities in which an object is manipulated under vision control, but no short or long term learning happens.

Unravelling the relationship between protein sequence and low-complexity regions entropies: Interactome implications.

Low-complexity regions are sub-sequences of biased composition in a protein sequence. The influence of these regions over protein evolution, specific functions and highly interactive capacities is well known. Although protein sequence entropy has been largely studied, its relationship with low-complexity regions and the subsequent effects on protein function remains unclear. In this work we propose a theoretical and empirical model integrating the sequence entropy with local complexity parameters. Our results indicate that the protein sequence entropy is related with the protein length, the entropies inside and outside the low-complexity regions as well as their number and average size. We found a small but significant increment in the sequence entropy of hubs proteins. In agreement with our theoretical model, this increment is highly dependent of the balance between the increment of protein length and average size of the low-complexity regions. Finally, our models and proteins analysis provide evidence supporting that modifications in the average size is more relevant in hubs proteins than changes in the number of low-complexity regions.

First- and second-trimester tests to predict stillbirth in unselected pregnant women: a systematic review and meta-analysis.

BACKGROUND: Several biophysical and biochemical tests have been proposed to predict stillbirth but their predictive ability remains unclear. OBJECTIVE: To assess the accuracy of tests performed during the first and/or second trimester of pregnancy to predict stillbirth in unselected women with singleton, structurally and chromosomally normal fetuses through use of formal methods for systematic reviews and meta-analytic techniques. SEARCH STRATEGY: Electronic databases, bibliographies and conference proceedings. SELECTION CRITERIA: Observational studies that evaluated the predictive accuracy for stillbirth of tests performed during the first two trimesters of pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers selected studies, assessed risk of bias and extracted data. Summary receiver operating characteristic curves, pooled sensitivities, specificities and likelihood ratios (LRs) were generated. Data were synthesised separately for stillbirth as a sole category and for specific stillbirth categories. MAIN RESULTS: Seventy-one studies, evaluating 16 single and five combined tests, met the inclusion criteria. A uterine artery pulsatility index >90th centile during the second trimester and low levels of pregnancy-associated plasma protein A (PAPP-A) during the first trimester had a moderate to high predictive accuracy for stillbirth related to placental abruption, small-for-gestational-age or pre-eclampsia (positive and negative LRs from 6.3 to 14.1, and from 0.1 to 0.4, respectively). All biophysical and biochemical tests assessed had a low predictive accuracy for stillbirth as a sole category. CONCLUSIONS: Currently, there is no clinically useful first-trimester or second-trimester test to predict stillbirth as a sole category. Uterine artery pulsatility index and maternal serum PAPP-A levels appeared to be good predictors of stillbirth related to placental dysfunction disorders.