Concurrent Progestogen and Cerclage to Reduce Preterm Birth: a multicenter international retrospective cohort.

OBJECTIVE: We aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth (sPTB) in singleton pregnancies METHODS: : This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016-June 2020. Exclusion criteria were: lack of documentation regarding whether progestogen was or was not prescribed, delivery outcome unavailable, and pregnancy termination (spontaneous or induced) prior to 16 weeks' gestation. Exposure of interest was progestogen use with cerclage placement, which included those who were continued on progestogen or who started progestogen after cerclage. Comparator was those without progestogen use after cerclage placement, which included those who had no progestogen use the whole pregnancy, or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. Primary outcome was sPTB <37 weeks. Secondary outcomes were sPTB <34 weeks, gestational age at delivery, composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, Grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, bronchopulmonary dysplasia. There was planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate (17-OHPC)), preterm birth history, and site. Continuous variables compared in adjusted analyses with ANCOVA and categorical variables compared with multivariable logistic regression adjusting for potential confounders with adjusted odds ratio (aOR). Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. RESULTS: During the study period, a total of 699 singletons met inclusion, N=561 in the progestogen with cerclage group, and N=138 with cerclage alone. Baseline characteristics were similar, except those in the progestogen group were more likely to have had a prior sPTB (61% vs 41%, p<0.001). Within the progestogen group, 52% were on 17-OHPC weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of sPTB<37 (31% vs 39% aOR 0.59 (0.39 - 0.89), p=0.01) and <34 weeks (19% vs 27%, aOR 0.55 (0.35 - 0.87), p=0.01), increased latency to spontaneous delivery (Hazard ratio to sPTB <37wk, 0.66 (0.49-0.90), p=0.009), and lower frequency of perinatal death (7% vs 16%, aOR 0.37 (0.20-0.67), p=0.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a prior preterm birth, those with ultrasound or exam-indicated cerclage, those that started progestogen therapy prior to cerclage, and in sites restricted to the United States. CONCLUSION: Use of progestogen with cerclage was associated with reduced rates of sPTB and early sPTB compared to cerclage alone. Although not powered for subgroups, the strength of evidence for benefit appeared greatest for those with ultrasound or exam-indicated cerclage, and with vaginal progesterone.

Screening of triploid banana population under natural and controlled black sigatoka disease for genomic selection.

The black sigatoka disease (BSD) is the most important foliar threat in banana production and breeding efforts against it should take advantage of genomic selection (GS) that has become one of the most explored tools to increase genetic gain, save time and reduce selection costs. In order to evaluate the potential of GS in banana for BSD, 210 triploid accessions were obtained from the African Banana and Plantain Research Center (CARBAP) to constitute a training population (TP). The variability in the population was assessed at the phenotypic level using BSD- and agronomic-related traits and at the molecular level using Single Nucleotide Polymorphism (SNPs). The analysis of variance showed a significant difference between accessions for almost all traits measured, while at the genomic group level; there was no significant difference for BSD-related traits. The Index of Non spotted leave among accessions ranged from 0.11 to 0.8. The accessions screening in controlled conditions confirmed the susceptibility of all genomic groups to BSD. The principal components analysis with phenotypic data revealed no clear diversity partition of the population. However, the structure analysis and the hierarchical clustering analysis with SNPs grouped the population into four (4) clusters and two (2) sub-populations respectively. The field and laboratory screening of the banana genomic selection TP confirmed that all genomic groups are susceptible to BSD but did not reveal any genetic structure while SNPs markers exhibited clear genetic structure and provided useful information in the perspective of applying genomic selection.

Tandem resection of multiple spinal schwannomas.

This video depicts the resection of three separate intradural extramedullary spinal tumors performed under the same anesthetic. Neuromonitoring was used to identify motor nerve roots, and laminoplasty was performed at the thoracolumbar junction to preserve alignment and minimize the risk of postoperative CSF leak.

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Mate selection: A useful approach to maximize genetic gain and control inbreeding in genomic and conventional oil palm (Elaeis guineensis Jacq.) hybrid breeding.

Genomic selection (GS) is an effective method for the genetic improvement of complex traits in plants and animals. Optimization approaches could be used in conjunction with GS to further increase its efficiency and to limit inbreeding, which can increase faster with GS. Mate selection (MS) typically uses a metaheuristic optimization algorithm, simulated annealing, to optimize the selection of individuals and their matings. However, in species with long breeding cycles, this cannot be studied empirically. Here, we investigated this aspect with forward genetic simulations on a high-performance computing cluster and massively parallel computing, considering the oil palm hybrid breeding example. We compared MS and simple methods of inbreeding management (limitation of the number of individuals selected per family, prohibition of self-fertilization and combination of these two methods), in terms of parental inbreeding and genetic progress over four generations of genomic selection and phenotypic selection. The results showed that, compared to the conventional method without optimization, MS could lead to significant decreases in inbreeding and increases in annual genetic progress, with the magnitude of the effect depending on MS parameters and breeding scenarios. The optimal solution retained by MS differed by five breeding characteristics from the conventional solution: selected individuals covering a broader range of genetic values, fewer individuals selected per full-sib family, decreased percentage of selfings, selfings preferentially made on the best individuals and unbalanced number of crosses among selected individuals, with the better an individual, the higher the number of times he is mated. Stronger slowing-down in inbreeding could be achieved with other methods but they were associated with a decreased genetic progress. We recommend that breeders use MS, with preliminary analyses to identify the proper parameters to reach the goals of the breeding program in terms of inbreeding and genetic gain.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial.

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). STUDY DESIGN: We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferred treatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. RESULTS: Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3 and 6.3±2.1 weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. CONCLUSION: In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging.

Adult neurogenesis is reduced during aging and impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections cumulatively across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in an accelerated decline in hippocampal acetylcholine signaling and a slow and progressing emergence of profound working memory deficits. These deficits were accompanied by compensatory reorganization of cholinergic dentate gyrus inputs with increased cholinergic innervation to the ventral hippocampus and recruitment of ventrally projecting neurons by the dorsal projection. While increased cholinergic innervation was dysfunctional and corresponded to overall decreases in cholinergic levels and signaling, it could be recruited to correct the resulting memory dysfunction even in old animals. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal cholinergic circuit across the lifespan.  It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.

An Overview of Mapping Quantitative Trait Loci in Peanut (Arachis hypogaea L.).

Quantitative Trait Loci (QTL) mapping has been thoroughly used in peanut genetics and breeding in spite of the narrow genetic diversity and the segmental tetraploid nature of the cultivated species. QTL mapping is helpful for identifying the genomic regions that contribute to traits, for estimating the extent of variation and the genetic action (i.e., additive, dominant, or epistatic) underlying this variation, and for pinpointing genetic correlations between traits. The aim of this paper is to review the recently published studies on QTL mapping with a particular emphasis on mapping populations used as well as traits related to kernel quality. We found that several populations have been used for QTL mapping including interspecific populations developed from crosses between synthetic tetraploids and elite varieties. Those populations allowed the broadening of the genetic base of cultivated peanut and helped with the mapping of QTL and identifying beneficial wild alleles for economically important traits. Furthermore, only a few studies reported QTL related to kernel quality. The main quality traits for which QTL have been mapped include oil and protein content as well as fatty acid compositions. QTL for other agronomic traits have also been reported. Among the 1261 QTL reported in this review, and extracted from the most relevant studies on QTL mapping in peanut, 413 (~33%) were related to kernel quality showing the importance of quality in peanut genetics and breeding. Exploiting the QTL information could accelerate breeding to develop highly nutritious superior cultivars in the face of climate change.

SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19.

SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.

Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging.

Adult neurogenesis is reduced during aging and impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections cumulatively across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in an accelerated decline in hippocampal acetylcholine signaling and a slow and progressing emergence of profound working memory deficits. These deficits were accompanied by compensatory reorganization of cholinergic dentate gyrus inputs with increased cholinergic innervation to the ventral hippocampus and recruitment of ventrally projecting neurons by the dorsal projection. While increased cholinergic innervation was dysfunctional and corresponded to overall decreases in cholinergic levels and signaling, it could be recruited to correct the resulting memory dysfunction even in old animals. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal cholinergic circuit across the lifespan. It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.

Analysis of genetic diversity and agronomic variation in banana sub-populations for genomic selection under drought stress in southern Benin.

In the perspective of investigating genomic selection (GS) among Musa genotypes in West and Central Africa, banana accessions were phenotyped under natural drought stress in Benin and genotyped using genotyping by sequencing. Sixty-one (61) accessions grouped into three major genomic groups AAA, AAB and ABB and those without genomic affiliation information were used. Variation within the population was determined by phenotypic variables while population structure and clustering analysis were carried out to understand the genetic diversity at the molecular level. Among the genomic groups evaluated, the group AAB showed the best performance for fruit weight at maturity, (3.41 ± 1.99 kg) and for plant height (198.46 ± 12.66 cm). At the accession level, HD 117 S1 and NIA 27 showed the best plant height (263.16 ± 20.98 cm) and the best fruit weight at maturity (9.43 ± 0.0 kg) respectively. Phenotypic data did not reveal clear genetic diversity among accessions; however, the genetic diversity was conspicuous at the molecular level using 5000 markers. The affiliations of local accessions in genomic groups were determined for the first time based on the phenotypic and molecular data obtained in this study. The knowledge generated allows the possibility to apply GS in banana.

Perspective for genomic-enabled prediction against black sigatoka disease and drought stress in polyploid species.

Genomic selection (GS) in plant breeding is explored as a promising tool to solve the problems related to the biotic and abiotic threats. Polyploid plants like bananas (Musa spp.) face the problem of drought and black sigatoka disease (BSD) that restrict their production. The conventional plant breeding is experiencing difficulties, particularly phenotyping costs and long generation interval. To overcome these difficulties, GS in plant breeding is explored as an alternative with a great potential for reducing costs and time in selection process. So far, GS does not have the same success in polyploid plants as with diploid plants because of the complexity of their genome. In this review, we present the main constraints to the application of GS in polyploid plants and the prospects for overcoming these constraints. Particular emphasis is placed on breeding for BSD and drought-two major threats to banana production-used in this review as a model of polyploid plant. It emerges that the difficulty in obtaining markers of good quality in polyploids is the first challenge of GS on polyploid plants, because the main tools used were developed for diploid species. In addition to that, there is a big challenge of mastering genetic interactions such as dominance and epistasis effects as well as the genotype by environment interaction, which are very common in polyploid plants. To get around these challenges, we have presented bioinformatics tools, as well as artificial intelligence approaches, including machine learning. Furthermore, a scheme for applying GS to banana for BSD and drought has been proposed. This review is of paramount impact for breeding programs that seek to reduce the selection cycle of polyploids despite the complexity of their genome.

IL-33 Induces an Antiviral Signature in Mast Cells but Enhances Their Permissiveness for Human Rhinovirus Infection.

Mast cells (MCs) are classically associated with allergic asthma but their role in antiviral immunity is unclear. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and can infect and replicate within MCs. The primary site of HRV infection is the airway epithelium and MCs localise to this site with increasing asthma severity. The asthma susceptibility gene, IL-33, encodes an epithelial-derived cytokine released following HRV infection but its impact on MC antiviral responses has yet to be determined. In this study we investigated the global response of LAD2 MCs to IL-33 stimulation using RNA sequencing and identified genes involved in antiviral immunity. In spite of this, IL-33 treatment increased permissiveness of MCs to HRV16 infection which, from the RNA-Seq data, we attributed to upregulation of ICAM1. Flow cytometric analysis confirmed an IL-33-dependent increase in ICAM1 surface expression as well as LDLR, the receptors used by major and minor group HRVs for cellular entry. Neutralisation of ICAM1 reduced the IL-33-dependent enhancement in HRV16 replication and release in both LAD2 MCs and cord blood derived MCs. These findings demonstrate that although IL-33 induces an antiviral signature in MCs, it also upregulates the receptors for HRV entry to enhance infection. This highlights the potential for a gene-environment interaction involving IL33 and HRV in MCs to contribute to virus-induced asthma exacerbations.

Spatially resolved deconvolution of the fibrotic niche in lung fibrosis.

A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFß/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis.

Towards an artificial human lung: modelling organ-like complexity to aid mechanistic understanding.

Respiratory diseases account for over 5 million deaths yearly and are a huge burden to healthcare systems worldwide. Murine models have been of paramount importance to decode human lung biology in vivo, but their genetic, anatomical, physiological and immunological differences with humans significantly hamper successful translation of research into clinical practice. Thus, to clearly understand human lung physiology, development, homeostasis and mechanistic dysregulation that may lead to disease, it is essential to develop models that accurately recreate the extraordinary complexity of the human pulmonary architecture and biology. Recent advances in micro-engineering technology and tissue engineering have allowed the development of more sophisticated models intending to bridge the gap between the native lung and its replicates in vitro Alongside advanced culture techniques, remarkable technological growth in downstream analyses has significantly increased the predictive power of human biology-based in vitro models by allowing capture and quantification of complex signals. Refined integrated multi-omics readouts could lead to an acceleration of the translational pipeline from in vitro experimental settings to drug development and clinical testing in the future. This review highlights the range and complexity of state-of-the-art lung models for different areas of the respiratory system, from nasal to large airways, small airways and alveoli, with consideration of various aspects of disease states and their potential applications, including pre-clinical drug testing. We explore how development of optimised physiologically relevant in vitro human lung models could accelerate the identification of novel therapeutics with increased potential to translate successfully from the bench to the patient's bedside.

Genome properties of key oil palm (Elaeis guineensis Jacq.) breeding populations.

A good knowledge of the genome properties of the populations makes it possible to optimize breeding methods, in particular genomic selection (GS). In oil palm (Elaeis guineensis Jacq), the world's main source of vegetable oil, this would provide insight into the promising GS results obtained so far. The present study considered two complex breeding populations, Deli and La Mé, with 943 individuals and 7324 single-nucleotide polymorphisms (SNPs) from genotyping-by-sequencing. Linkage disequilibrium (LD), haplotype sharing, effective size (Ne), and fixation index (Fst) were investigated. A genetic linkage map spanning 1778.52 cM and with a recombination rate of 2.85 cM/Mbp was constructed. The LD at r2=0.3, considered the minimum to get reliable GS results, spanned over 1.05 cM/0.22 Mbp in Deli and 0.9 cM/0.21 Mbp in La Mé. The significant degree of differentiation existing between Deli and La Mé was confirmed by the high Fst value (0.53), the pattern of correlation of SNP heterozygosity and allele frequency among populations, and the decrease of persistence of LD and of haplotype sharing among populations with increasing SNP distance. However, the level of resemblance between the two populations over short genomic distances (correlation of r values between populations >0.6 for SNPs separated by <0.5 cM/1 kbp and percentage of common haplotypes >40% for haplotypes <3600 bp/0.20 cM) likely explains the superiority of GS models ignoring the parental origin of marker alleles over models taking this information into account. The two populations had low Ne (<5). Population-specific genetic maps and reference genomes are recommended for future studies.

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

Sequence of visual cortex stimulation affects phosphene brightness in blind subjects.

BACKGROUND: Visual cortical prostheses (VCP) could potentially benefit a majority of the blind population. Feasibility testing of these VCP opens new avenues to characterize stimulation of visual cortex in blind subjects. OBJECTIVE/HYPOTHESIS: To determine if sequential stimulation of visual cortex produces a perception bias in phosphene brightness. METHODS: We stimulated three blind subjects implanted with the Orion array with sequences of two and three electrodes and asked them to determine the brighter phosphene, using interval forced-choice paradigms. We selected a set of reference electrodes as the constant stimuli across sequences and compared across three different amplitude levels keeping all other stimulation parameters fixed across electrodes. RESULTS: For two subjects, we measured a significant increase in the probability of perceiving a lower-level amplitude just as bright or brighter than a higher-level amplitude when stimulated later in the sequence (p < 0.001, Wilcoxon rank sum test). The probability of reference electrodes selected as brighter was also higher during the second phase, across most amplitude comparisons. For the third subject, there were measurable but not significant changes, where the first stimuli were perceived as brighter. The effects were consistent within subjects in the three-electrode sequences, where the probability of the reference electrode selected as brighter was correlated to when it was presented in the sequence. CONCLUSIONS: We showed evidence of temporal interactions in non-overlapping sequences of electrodes, where the direction of the effect was subject specific but consistent across a variety of electrode locations and current amplitude levels.

Improving the accuracy of genomic predictions in an outcrossing species with hybrid cultivars between heterozygote parents: a case study of oil palm (Elaeis guineensis Jacq.).

Genomic selection (GS) is a method of marker-assisted selection revolutionizing crop improvement, but it can still be optimized. For hybrid breeding between heterozygote parents of different populations or species, specific aspects can be considered to increase GS accuracy: (1) training population genotyping, i.e., only genotyping the hybrid parents or also a sample of hybrid individuals, and (2) marker effects modeling, i.e., using population-specific effects of single nucleotide polymorphism alleles model (PSAM) or across-population SNP genotype model (ASGM). Here, this was investigated empirically for the prediction of the performances of oil palm hybrids for yield traits. The GS model was trained on 352 hybrid crosses and validated on 213 independent hybrid crosses. The training and validation hybrid parents and 399 training hybrid individuals were genotyping by sequencing. Despite the small proportion of hybrid individuals genotyped and low parental heterozygosity, GS prediction accuracy increased on average by 5% (range 1.4-31.3%, depending on trait and model) when training was done using genomic data on hybrids and parents compared with only parental genomic data. With ASGM, GS prediction accuracy increased on average by 3% (- 10.2 to 40%, depending on trait and genotyping strategy) compared with PSAM. We conclude that the best GS strategy for oil palm is to aggregate genomic data of parents and hybrid individuals and to ignore the parental origin of marker alleles (ASGM). To gain a better insight into these results, future studies should examine the respective effect of capturing genetic variability within crosses and taking segregation distortion into account when genotyping hybrid individuals, and investigate the factors controlling the relative performances of ASGM and PSAM in hybrid crops.