A randomised trial of early palliative care for maternal stress in infants prenatally diagnosed with single-ventricle heart disease

AbstractChildren with single-ventricle disease experience high mortality and complex care. In other life-limiting childhood illnesses, paediatric palliative care may mitigate maternal stress. We hypothesised that early palliative care in the single-ventricle population may have the same benefit for mothers. In this pilot randomised trial of early palliative care, mothers of infants with prenatal single-ventricle diagnoses completed surveys measuring depression, anxiety, coping, and quality of life at a prenatal visit and neonatal discharge. Infants were randomised to receive early palliative care – structured evaluation, psychosocial/spiritual, and communication support before surgery – or standard care. Among 56 eligible mothers, 40 enrolled and completed baseline surveys; 38 neonates were randomised, 18 early palliative care and 20 standard care; and 34 postnatal surveys were completed. Baseline Beck Depression Inventory-II and State-Trait Anxiety Index scores exceeded normal pregnant sample scores (mean 13.76±8.46 versus 7.0±5.0 and 46.34±12.59 versus 29.8±6.35, respectively; p=0.0001); there were no significant differences between study groups. The early palliative care group had a decrease in prenatal to postnatal State-Trait Anxiety Index scores (−7.6 versus 0.3 in standard care, p=0.02), higher postnatal Brief Cope Inventory positive reframing scores (p=0.03), and a positive change in PedsQL Family Impact Module communication and family relationships scores (effect size 0.46 and 0.41, respectively). In conclusion, these data show that mothers of infants with single-ventricle disease experience significant depression and anxiety prenatally. Early palliative care resulted in decreased maternal anxiety, improved maternal positive reframing, and improved communication and family relationships.</jats:p

BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery

Single-nucleotide variation and gene expression of disease samples represent important resources for biomarker discovery. Many databases have been built to host and make available such data to the community, but these databases are frequently limited in scope and/or content. BioMuta, a database of cancer-associated single-nucleotide variations, and BioXpress, a database of cancer-associated differentially expressed genes and microRNAs, differ from other disease-associated variation and expression databases primarily through the aggregation of data across many studies into a single source with a unified representation and annotation of functional attributes. Early versions of these resources were initiated by pilot funding for specific research applications, but newly awarded funds have enabled hardening of these databases to production-level quality and will allow for sustained development of these resources for the next few years. Because both resources were developed using a similar methodology of integration, curation, unification, and annotation, we present BioMuta and BioXpress as allied databases that will facilitate a more comprehensive view of gene associations in cancer. BioMuta and BioXpress are hosted on the High-performance Integrated Virtual Environment (HIVE) server at the George Washington University at https://hive.biochemistry.gwu.edu/biomuta and https://hive.biochemistry.gwu.edu/bioxpress, respectively

BioXpress: an integrated RNA-seq-derived gene expression database for pan-cancer analysis.

BioXpress is a gene expression and cancer association database in which the expression levels are mapped to genes using RNA-seq data obtained from The Cancer Genome Atlas, International Cancer Genome Consortium, Expression Atlas and publications. The BioXpress database includes expression data from 64 cancer types, 6361 patients and 17 469 genes with 9513 of the genes displaying differential expression between tumor and normal samples. In addition to data directly retrieved from RNA-seq data repositories, manual biocuration of publications supplements the available cancer association annotations in the database. All cancer types are mapped to Disease Ontology terms to facilitate a uniform pan-cancer analysis. The BioXpress database is easily searched using HUGO Gene Nomenclature Committee gene symbol, UniProtKB/RefSeq accession or, alternatively, can be queried by cancer type with specified significance filters. This interface along with availability of pre-computed downloadable files containing differentially expressed genes in multiple cancers enables straightforward retrieval and display of a broad set of cancer-related genes

An Empirical reionization history model inferred from the low-redshift Lyman continuum survey and the star-forming galaxies at z>8z>8

We present a new analysis of the rest-frame UV and optical spectra of a sample of three $z>8$ galaxies discovered behind the gravitational lensing cluster RX\,J2129.4+0009. We combine these observations with $z>7.5$ galaxies from the literature, for which similar measurements are available. As already pointed out in other studies, the high [\oiii]$\lambda$5007/[\oii]$\lambda$3727 ratios ($O_{32}$) and steep UV continuum slopes ($\beta$) are consistent with the values observed for low redshift Lyman continuum emitters, suggesting that such galaxies contribute to the ionizing budget of the intergalactic medium. We construct a logistic regression model to estimate the probability of a galaxy being a Lyman continuum emitter based on the measured \MUV, $\beta$, and $O_{32}$. Using this probability and the UV luminosity function, we construct an empirical model that estimates the contribution of high redshift galaxies to reionization. The preferred scenario in our analysis shows that at $z\sim8$, the average escape fraction of the galaxy population (i.e., including both LyC emitters and non-emitters) varies with \MUV, with intermediate UV luminosity ($-19<M_{UV}<-16$) galaxies having larger escape fraction. Galaxies with faint UV luminosity ($-16<M_{UV}<-13.5$) contribute most of the ionizing photons. The relative contribution of faint versus bright galaxies depends on redshift, with the intermediate UV galaxies becoming more important over time. UV bright galaxies, although more likely to be LCEs at a given log($O_{32}$) and $\beta$, contribute the least of the total ionizing photon budget.Comment: 10 pages, 7 figures, accepted by MNRA

Effects of COVID-19 vaccination and previous SARS-CoV-2 infection on omicron infection and severe outcomes in children under 12 years of age in the USA: an observational cohort study

Background Data on the protection conferred by COVID-19 vaccination and previous SARS-CoV-2 infection against omicron (B.1.1.529) infection in young children are scarce. We aimed to estimate the time-varying effects of primary and booster COVID-19 vaccination and previous SARS-CoV-2 infection on subsequent omicron infection and severe illness (hospital admission or death) in children younger than 12 years of age. Methods In this observational cohort study, we obtained individual-level records on vaccination with the BNT162b2 and mRNA-1273 vaccines and clinical outcomes from the North Carolina COVID-19 Surveillance System and the COVID-19 Vaccine Management System for 1 368 721 North Carolina residents aged 11 years or younger from Oct 29, 2021 (Oct 29, 2021 for children aged 5–11 years and June 17, 2022 for children aged 0–4 years), to Jan 6, 2023. We used Cox regression to estimate the time-varying effects of primary and booster vaccination and previous infection on the risks of omicron infection, hospital admission, and death. Findings For children 5–11 years of age, the effectiveness of primary vaccination against infection, compared with being unvaccinated, was 59·9% (95% CI 58·5–61·2) at 1 month, 33·7% (32·6–34·8) at 4 months, and 14·9% (95% CI 12·3–17·5) at 10 months after the first dose. Compared with primary vaccination only, the effectiveness of a monovalent booster dose after 1 month was 24·4% (14·4–33·2) and that of a bivalent booster dose was 76·7% (45·7–90·0). The effectiveness of omicron infection against reinfection was 79·9% (78·8–80·9) after 3 months and 53·9% (52·3–55·5) after 6 months. For children 0–4 years of age, the effectiveness of primary vaccination against infection, compared with being unvaccinated, was 63·8% (57·0–69·5) at 2 months and 58·1% (48·3–66·1) at 5 months after the first dose, and the effectiveness of omicron infection against reinfection was 77·3% (75·9–78·6) after 3 months and 64·7% (63·3–66·1) after 6 months. For both age groups, vaccination and previous infection had better effectiveness against severe illness as measured by hospital admission or death as a composite endpoint than against infection. Interpretation The BNT162b2 and mRNA-1273 vaccines were effective against omicron infection and severe outcomes in children younger than 12 years, although the effectiveness decreased over time. Bivalent boosters were more effective than monovalent boosters. Immunity acquired via omicron infection was high and waned gradually over time. These findings can be used to develop effective prevention strategies against COVID-19 in children younger than 12 years

Association of Primary and Booster Vaccination and Prior Infection With SARS-CoV-2 Infection and Severe COVID-19 Outcomes

Data about the association of COVID-19 vaccination and prior SARS-CoV-2 infection with risk of SARS-CoV-2 infection and severe COVID-19 outcomes may guide prevention strategies.To estimate the time-varying association of primary and booster COVID-19 vaccination and prior SARS-CoV-2 infection with subsequent SARS-CoV-2 infection, hospitalization, and death.Cohort study of 10.6 million residents in North Carolina from March 2, 2020, through June 3, 2022.COVID-19 primary vaccine series and boosters and prior SARS-CoV-2 infection.Rate ratio (RR) of SARS-CoV-2 infection and hazard ratio (HR) of COVID-19–related hospitalization and death.The median age among the 10.6 million participants was 39 years; 51.3% were female, 71.5% were White, and 9.9% were Hispanic. As of June 3, 2022, 67% of participants had been vaccinated. There were 2 771 364 SARS-CoV-2 infections, with a hospitalization rate of 6.3% and mortality rate of 1.4%. The adjusted RR of the primary vaccine series compared with being unvaccinated against infection became 0.53 (95% CI, 0.52-0.53) for BNT162b2, 0.52 (95% CI, 0.51-0.53) for mRNA-1273, and 0.51 (95% CI, 0.50-0.53) for Ad26.COV2.S 10 months after the first dose, but the adjusted HR for hospitalization remained at 0.29 (95% CI, 0.24-0.35) for BNT162b2, 0.27 (95% CI, 0.23-0.32) for mRNA-1273, and 0.35 (95% CI, 0.29-0.42) for Ad26.COV2.S and the adjusted HR of death remained at 0.23 (95% CI, 0.17-0.29) for BNT162b2, 0.15 (95% CI, 0.11-0.20) for mRNA-1273, and 0.24 (95% CI, 0.19-0.31) for Ad26.COV2.S. For the BNT162b2 primary series, boosting in December 2021 with BNT162b2 had the adjusted RR relative to primary series of 0.39 (95% CI, 0.38-0.40) and boosting with mRNA-1273 had the adjusted RR of 0.32 (95% CI, 0.30-0.34) against infection after 1 month and boosting with BNT162b2 had the adjusted RR of 0.84 (95% CI, 0.82-0.86) and boosting with mRNA-1273 had the adjusted RR of 0.60 (95% CI, 0.57-0.62) after 3 months. Among all participants, the adjusted RR of Omicron infection compared with no prior infection was estimated at 0.23 (95% CI, 0.22-0.24) against infection, and the adjusted HRs were 0.10 (95% CI, 0.07-0.14) against hospitalization and 0.11 (95% CI, 0.08-0.15) against death after 4 months.Receipt of primary COVID-19 vaccine series compared with being unvaccinated, receipt of boosters compared with primary vaccination, and prior infection compared with no prior infection were all significantly associated with lower risk of SARS-CoV-2 infection (including Omicron) and resulting hospitalization and death. The associated protection waned over time, especially against infection

Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina

Background The duration of protection afforded by coronavirus disease 2019 (Covid-19) vaccines in the United States is unclear. Whether the increase in postvaccination infections during the summer of 2021 was caused by declining immunity over time, the emergence of the B.1.617.2 (delta) variant, or both is unknown. Methods We extracted data regarding Covid-19–related vaccination and outcomes during a 9-month period (December 11, 2020, to September 8, 2021) for approximately 10.6 million North Carolina residents by linking data from the North Carolina Covid-19 Surveillance System and the Covid-19 Vaccine Management System. We used a Cox regression model to estimate the effectiveness of the BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), and Ad26.COV2.S (Johnson & Johnson–Janssen) vaccines in reducing the current risks of Covid-19, hospitalization, and death, as a function of time elapsed since vaccination. Results For the two-dose regimens of messenger RNA (mRNA) vaccines BNT162b2 (30 μg per dose) and mRNA-1273 (100 μg per dose), vaccine effectiveness against Covid-19 was 94.5% (95% confidence interval [CI], 94.1 to 94.9) and 95.9% (95% CI, 95.5 to 96.2), respectively, at 2 months after the first dose and decreased to 66.6% (95% CI, 65.2 to 67.8) and 80.3% (95% CI, 79.3 to 81.2), respectively, at 7 months. Among early recipients of BNT162b2 and mRNA-1273, effectiveness decreased by approximately 15 and 10 percentage points, respectively, from mid-June to mid-July, when the delta variant became dominant. For the one-dose regimen of Ad26.COV2.S (5×1010 viral particles), effectiveness against Covid-19 was 74.8% (95% CI, 72.5 to 76.9) at 1 month and decreased to 59.4% (95% CI, 57.2 to 61.5) at 5 months. All three vaccines maintained better effectiveness in preventing hospitalization and death than in preventing infection over time, although the two mRNA vaccines provided higher levels of protection than Ad26.COV2.S. Conclusions All three Covid-19 vaccines had durable effectiveness in reducing the risks of hospitalization and death. Waning protection against infection over time was due to both declining immunity and the emergence of the delta variant. (Funded by a Dennis Gillings Distinguished Professorship and the National Institutes of Health.

Disorder Dynamics in Battery Nanoparticles During Phase Transitions Revealed by Operando Single-Particle Diffraction

Structural and ion-ordering phase transitions limit the viability of sodium-ion intercalation materials in grid scale battery storage by reducing their lifetime. However, the combination of phenomena in nanoparticulate electrodes creates complex behavior that is difficult to investigate, especially on the single nanoparticle scale under operating conditions. In this work, operando single-particle x-ray diffraction (oSP-XRD) is used to observe single-particle rotation, interlayer spacing, and layer misorientation in a functional sodium-ion battery. oSP-XRD is applied to Na$_{2/3}$[Ni$_{1/3}$Mn$_{2/3}$]O$_{2}$, an archetypal P2-type sodium-ion positive electrode material with the notorious P2-O2 phase transition induced by sodium (de)intercalation. It is found that during sodium extraction, the misorientation of crystalline layers inside individual particles increases before the layers suddenly align just prior to the P2-O2 transition. The increase in the long-range order coincides with an additional voltage plateau signifying a phase transition prior to the P2-O2 transition. To explain the layer alignment, a model for the phase evolution is proposed that includes a transition from localized to correlated Jahn-Teller distortions. The model is anticipated to guide further characterization and engineering of sodium-ion intercalation materials with P2-O2 type transitions. oSP-XRD therefore opens a powerful avenue for revealing complex phase behavior in heterogeneous nanoparticulate systems.Comment: 23 pages, 4 main figures, 9 supplemental figure