Differential transcript usage analysis incorporating quantification uncertainty via compositional measurement error regression modeling.

Differential transcript usage (DTU) occurs when the relative expression of multiple transcripts arising from the same gene changes between different conditions. Existing approaches to detect DTU often rely on computational procedures that can have speed and scalability issues as the number of samples increases. Here we propose a new method, CompDTU, that uses compositional regression to model the relative abundance proportions of each transcript that are of interest in DTU analyses. This procedure leverages fast matrix-based computations that make it ideally suited for DTU analysis with larger sample sizes. This method also allows for the testing of and adjustment for multiple categorical or continuous covariates. Additionally, many existing approaches for DTU ignore quantification uncertainty in the expression estimates for each transcript in RNA-seq data. We extend our CompDTU method to incorporate quantification uncertainty leveraging common output from RNA-seq expression quantification tool in a novel method CompDTUme. Through several power analyses, we show that CompDTU has excellent sensitivity and reduces false positive results relative to existing methods. Additionally, CompDTUme results in further improvements in performance over CompDTU with sufficient sample size for genes with high levels of quantification uncertainty, while also maintaining favorable speed and scalability. We motivate our methods using data from the Cancer Genome Atlas Breast Invasive Carcinoma data set, specifically using RNA-seq data from primary tumors for 740 patients with breast cancer. We show greatly reduced computation time from our new methods as well as the ability to detect several novel genes with significant DTU across different breast cancer subtypes.

An HIV-1 risk assessment tool for women aged 15-49 in African countries: A pooled analysis across 15 nationally representative surveys.

BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.

Evidence of bacterial biofilms within acute wounds: a systematic review.

OBJECTIVE: The prevalence and role of biofilm formation in acute wounds has seldom been investigated. Understanding the presence of biofilm in acute wounds would allow earlier, biofilm-targeted management, thus decreasing the morbidity and mortality associated with wound infection, improving patient experience and potentially reducing healthcare costs. The purpose of this study was to summarise the evidence for biofilm formation within acute wounds. METHOD: We conducted a systematic literature review for studies which reported evidence of bacterial biofilm formation in acute wounds. An electronic search of four databases was carried out, without restrictions on date. The search terms included 'bacteria', 'biofilm', 'acute' and 'wound'. RESULTS: A total of 13 studies met the inclusion criteria. Of the studies, 69.2% showed evidence of biofilm formation within 14 days of acute wound formation, with 38.5% showing evidence of biofilm 48 hours after wound formed. CONCLUSION: The evidence from this review suggests that biofilm formation plays a greater role within acute wounds than previously considered.

Real-time detection of volatile metabolites enabling species-level discrimination of bacterial biofilms associated with wound infection.

AIMS: The main aim of this study was to investigate the real-time detection of volatile metabolites for the species-level discrimination of pathogens associated with clinically relevant wound infection, when grown in a collagen wound biofilm model. METHODS AND RESULTS: This work shows that Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes produce a multitude of volatile compounds when grown as biofilms in a collagen-based biofilm model. The real-time detection of these complex volatile profiles using selected ion flow tube mass spectrometry and the use of multivariate statistical analysis on the resulting data can be used to successfully differentiate between the pathogens studied. CONCLUSIONS: The range of bacterial volatile compounds detected between the species studied vary and are distinct. Discrimination between bacterial species using real-time detection of volatile metabolites and multivariate statistical analysis was successfully demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: Development of rapid point-of-care diagnostics for wound infection would improve diagnosis and patient care. Such technological approaches would also facilitate the appropriate use of antimicrobials, minimizing the emergence of antimicrobial resistance. This study further develops the use of volatile metabolite detection as a new diagnostic approach for wound infection.

Knowledge and decisions about maternal immunisation by pregnant women in Aotearoa New Zealand.

BACKGROUND: Maternal vaccinations for influenza and pertussis are recommended in New Zealand to protect mothers and their infant from infection. However, maternal immunisation coverage in New Zealand is suboptimal. Furthermore, there is unacceptable inequitable maternal immunisation rates across the country with Maori and Pacific women having significantly lower maternal immunisation rates than those of other New Zealanders. METHODS: This research set out to explore what pregnant/recently pregnant Maori and Pacific women knew about immunisation during pregnancy and what factors influenced their decision to be vaccinated. A semi-structured interview guide was developed with questions focusing on knowledge of pertussis and influenza vaccination during pregnancy and decision-making. Maori and Pacific women aged over 16 years were purposively sampled and interviewed in Dunedin and Gisborne, New Zealand between May and August 2021. Interviews were analysed following a directed qualitative content approach. Data were arranged into coding nodes based on the study aims (deductive analysis) informed by previous literature and within these participant experiences were inductively coded into themes and subthemes. RESULTS: Not all women were aware of maternal vaccine recommendations or they diseases they protected against. Many underestimated how dangerous influenza and pertussis could be and some were more concerned about potential harms of the vaccine. Furthermore, understanding potential harms of infection and protection provided by vaccination did not necessarily mean women would choose to be vaccinated. Those who decided to vaccinate felt well-informed, had vaccination recommended by their healthcare provider, and did so to protect their and their infant's health. Those who decided against vaccination were concerned about safety of the vaccines, lacked the information they needed, were not offered the vaccine, or did not consider vaccination a priority. CONCLUSIONS: There is a lack of understanding about vaccine benefits and risks of vaccine-preventable diseases which can result in the reinforcement of negative influences such as the fear of side effects. Furthermore, if vaccine benefits are not understood, inaccessibility of vaccines and the precedence of other life priorities may prevent uptake. Being well-informed and supported to make positive decisions to vaccinate in pregnancy is likely to improve vaccine coverage in Maori and Pacific Island New Zealanders.

Assessment of mutations induced by cold atmospheric plasma jet treatment relative to known mutagens in Escherichia coli.

The main bactericidal components of cold atmospheric plasma (CAP) are thought to be reactive oxygen and nitrogen species (RONS) and UV-radiation, both of which have the capacity to cause DNA damage and mutations. Here, the mutagenic effects of CAP on Escherichia coli were assessed in comparison to X- and UV-irradiation. DNA damage and mutagenesis were screened for using a diffusion-based DNA fragmentation assay and modified Ames test, respectively. Mutant colonies obtained from the latter were quantitated and sequenced. CAP was found to elicit a similar mutation spectrum to X-irradiation, which did not resemble that for UV implying that CAP-produced RONS are more likely the mutagenic component of CAP. CAP treatment was also shown to promote resistance to the antibiotic ciprofloxacin. Our data suggest that CAP treatment has mutagenic effects that may have important phenotypic consequences.

Hospitalisations related to systemic sclerosis and the impact of interstitial lung disease. Analysis of patients hospitalised at the University of Michigan, USA.

OBJECTIVES: To determine the primary reason for hospitalisations in systemic sclerosis (SSc) and impact of underlying interstitial lung disease (ILD) in a tertiary scleroderma centre. METHODS: A retrospective analysis on a subset of a scleroderma cohort from 2011-2019 was performed to assess causes for hospitalisations and mortality. A chart review was performed to extract demographics, primary reason for hospitalisation and inpatient mortality. Admissions were classified as SSc (if hospitalisation reason was related to primary organ dysfunction) and non-SSc related causes. RESULTS: The mean age of the cohort was 53.1 years, 78% were women, and the mean disease duration was 5.2 years. Among 484 patients, 182 (37.6%) were admitted for a total of 634 admissions. In 382 SSc-related admissions, pulmonary hypertension (12.0%) and gastrointestinal dysmotility (11.0%), were major causes of urgent admissions; management of digital vasculopathy (26.1%) was the major reason for elective admissions. In 252 non-SSc related admissions, infection (respiratory:11.5%, skin and soft tissue: 6.3%) was the major reason for urgent admissions, and elective surgery (21.4%) was the major reason for elective admissions. We found 65% of all patients had underlying ILD and a greater proportion of patients with ILD were hospitalised (122 patients). Overall inpatient mortality was 9.3% and the leading cause for mortality was progressive pulmonary hypertension. CONCLUSIONS: Among a large cohort of SSc patients who are followed at a tertiary scleroderma centre, 37.6 % had hospital admissions, while worsening pulmonary hypertension, ILD, cardiac involvement and infectious complications were the major cause of mortality and morbidity.

Performance of Anti-Topoisomerase I Antibody Testing by Multiple-Bead, Enzyme-Linked Immunosorbent Assay and Immunodiffusion in a University Setting.

BACKGROUND/OBJECTIVE: The criterion standard for anti-topoisomerase I antibody (anti-topo I antibody) testing in systemic sclerosis (SSc) uses immunodiffusion (ID) techniques, but enzyme-linked immunosorbent assay (ELISA) and multiple-bead technology are often used in current settings to save time and cost. Our aim was to assess the performance of the multiple-bead assay, ELISA, and ID testing methods. METHODS: We conducted a retrospective study of patients at the University of Michigan whose extractable nuclear antigen 10 autoantibody panel tested positive for the anti-topo I antibody by multiple-bead technology during a 1-year period. All samples positive by multiple-bead assay were sent to the RDL Laboratories and reflexed for ELISA, and all anti-topo I antibodies positive by ELISA were further tested by ID. Clinical data were reviewed by a rheumatologist and assessed for presence of SSc. Data were analyzed via frequency tables. RESULTS: Approximately 9500 extractable nuclear antigen 10 panels were ordered by physicians at the University of Michigan. Of these, 129 patients were positive for the anti-topo I antibody by multiple-bead assay, 51 were positive by multiple-bead assay and ELISA, and 21 were positive by multiple-bead assay, ELISA, and ID. We found that 26.4% of patients positive by multiple-bead assay, 47.1% positive by multiple-bead assay and ELISA, and 95.2% positive by multiple-bead assay, ELISA, and ID had SSc. CONCLUSIONS: Multiple-bead assays have a high rate of false-positive results for the anti-topo I antibody in patients without clinical evidence of SSc. A stepwise approach of confirmation of positive multiple-bead assay results using both ELISA and ID improves the predictive value of antibody testing for the diagnosis of SSc.

Impact of the revised haemodynamic definition on the diagnosis of pulmonary hypertension in patients with systemic sclerosis.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in systemic sclerosis (SSc). We explored the impact of the updated haemodynamic definition of pulmonary hypertension (PH), as proposed by the 6th World Symposium on Pulmonary Hypertension. METHODS: In this single-centre retrospective analysis, patients with SSc who had right heart catheterisation (RHC) were included. We compared the prior PH definition to the updated PH definition. The prior definition classified PH as mean pulmonary arterial pressure (mPAP) ≥25 mmHg and further divided into pre-capillary PH (PAH and PH due to lung disease and/or hypoxia), post-capillary PH, and combined pre- and post-capillary PH groups. For the updated definition, PH was classified as mPAP >20 mmHg and further divided into the different groups. We validated our findings in the DETECT cohort. RESULTS: Between 2005 and March 2019, 268 RHCs were performed in this single-centre cohort. Using the prior definition, 137 (51%) were diagnosed with PH, with 89 classified as pre-capillary PH (56 with PAH and 33 with PH due to lung disease and/or hypoxia), 29 as post-capillary PH, and 19 as combined pre- and post-capillary PH. When the updated definition was applied to the cohort, seven out of 131 (5%) with no PH were reclassified to pre-capillary PH (PAH (n=1), PH due to lung disease (n=3) and post-capillary PH (n=3)). In those with mPAP 21-24 mmHg, with no left heart or significant lung disease, one out of 28 (4%) in our cohort and four out of 36 (11%) in the DETECT cohort were reclassified as PAH. CONCLUSION: The updated PH definition does not appear to have a significant impact on the diagnosis of PH in two different screening cohorts.

An in vitro collagen perfusion wound biofilm model; with applications for antimicrobial studies and microbial metabolomics.

BACKGROUND: The majority of in vitro studies of medically relevant biofilms involve the development of biofilm on an inanimate solid surface. However, infection in vivo consists of biofilm growth on, or suspended within, the semi-solid matrix of the tissue, whereby current models do not effectively simulate the nature of the in vivo environment. This paper describes development of an in vitro method for culturing wound associated microorganisms in a system that combines a semi-solid collagen gel matrix with continuous flow of simulated wound fluid. This enables culture of wound associated reproducible steady state biofilms under conditions that more closely simulate the dynamic wound environment. To demonstrate the use of this model the antimicrobial kinetics of ceftazidime, against both mature and developing Pseudomonas aeruginosa biofilms, was assessed. In addition, we have shown the potential application of this model system for investigating microbial metabolomics by employing selected ion flow tube mass spectrometry (SIFT-MS) to monitor ammonia and hydrogen cyanide production by Pseudomonas aeruginosa biofilms in real-time. RESULTS: The collagen wound biofilm model facilitates growth of steady-state reproducible Pseudomonas aeruginosa biofilms under wound like conditions. A maximum biofilm density of 1010 cfu slide- 1 was achieved by 30 h of continuous culture and maintained throughout the remainder of the experiment. Treatment with ceftazidime at a clinically relevant dose resulted in a 1.2-1.6 log reduction in biofilm density at 72 h compared to untreated controls. Treatment resulted in loss of complex biofilm architecture and morphological changes to bacterial cells, visualised using confocal microscopy. When monitoring the biofilms using SIFT-MS, ammonia and hydrogen cyanide levels peaked at 12 h at 2273 ppb (±826.4) and 138 ppb (±49.1) respectively and were detectable throughout experimentation. CONCLUSIONS: The collagen wound biofilm model has been developed to facilitate growth of reproducible biofilms under wound-like conditions. We have successfully used this method to: (1) evaluate antimicrobial efficacy and kinetics, clearly demonstrating the development of antimicrobial tolerance in biofilm cultures; (2) characterise volatile metabolite production by P. aeruginosa biofilms, demonstrating the potential use of this method in metabolomics studies.

Reliability, construct validity and responsiveness to change of the PROMIS-29 in systemic sclerosis-associated interstitial lung disease.

OBJECTIVES: PROMIS-29 is a generic health-related quality of life instrument. Our objective was to assess the reliability, construct validity, and responsiveness to change of PROMIS-29 in systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: Seventy-three participants with SSc-ILD were administered patient reported outcomes (PROs) at baseline and follow-up visits which included PROMIS-29 and other measures of generic health, dyspnea, and cough instruments. We assessed internal consistency reliability using Cronbach's α, an alpha of ≥ 0.70 was considered satisfactory. We assessed the responsiveness to change using linear regression models. RESULTS: Mean age of the participants was 51.9 years and the mean disease duration was 7.9 years after first non-Raynaud's symptom. Of the 73 participants, 56.2% were classified as diffuse SSc and 26% limited SSc. The baseline (mean ± SD) FVC % predicted was 73.9±15.5 with a DLCO % predicted of 57.7±21.1; 95.9% had fibrotic NSIP pattern on HRCT. PROMIS-29 scores were 0.2 to 0.9 SD below the US population. Cronbach's α reliability was acceptable for all domains (ranged from 0.77 to 0.98). All scales showed statistically significant correlations with hypothesised PROMIS-29 domains (p≤0.05 for all comparisons). PROMIS-29 showed none-to-small discriminatory ability in comparison with physiologic measures (FVC and DLCO). There was no significant relationship between the change in FVC versus the change in PROMIS-29 measures over time. CONCLUSIONS: PROMIS-29 has adequate reliability and construct validity for evaluation in SSc-ILD. It has moderate-to-large correlations with other PROs. The PROMIS-29 domains were not found to change over time in this cohort, likely due to stable nature of the observational cohort.

A data-driven approach to predicting diabetes and cardiovascular disease with machine learning.

BACKGROUND: Diabetes and cardiovascular disease are two of the main causes of death in the United States. Identifying and predicting these diseases in patients is the first step towards stopping their progression. We evaluate the capabilities of machine learning models in detecting at-risk patients using survey data (and laboratory results), and identify key variables within the data contributing to these diseases among the patients. METHODS: Our research explores data-driven approaches which utilize supervised machine learning models to identify patients with such diseases. Using the National Health and Nutrition Examination Survey (NHANES) dataset, we conduct an exhaustive search of all available feature variables within the data to develop models for cardiovascular, prediabetes, and diabetes detection. Using different time-frames and feature sets for the data (based on laboratory data), multiple machine learning models (logistic regression, support vector machines, random forest, and gradient boosting) were evaluated on their classification performance. The models were then combined to develop a weighted ensemble model, capable of leveraging the performance of the disparate models to improve detection accuracy. Information gain of tree-based models was used to identify the key variables within the patient data that contributed to the detection of at-risk patients in each of the diseases classes by the data-learned models. RESULTS: The developed ensemble model for cardiovascular disease (based on 131 variables) achieved an Area Under - Receiver Operating Characteristics (AU-ROC) score of 83.1% using no laboratory results, and 83.9% accuracy with laboratory results. In diabetes classification (based on 123 variables), eXtreme Gradient Boost (XGBoost) model achieved an AU-ROC score of 86.2% (without laboratory data) and 95.7% (with laboratory data). For pre-diabetic patients, the ensemble model had the top AU-ROC score of 73.7% (without laboratory data), and for laboratory based data XGBoost performed the best at 84.4%. Top five predictors in diabetes patients were 1) waist size, 2) age, 3) self-reported weight, 4) leg length, and 5) sodium intake. For cardiovascular diseases the models identified 1) age, 2) systolic blood pressure, 3) self-reported weight, 4) occurrence of chest pain, and 5) diastolic blood pressure as key contributors. CONCLUSION: We conclude machine learned models based on survey questionnaire can provide an automated identification mechanism for patients at risk of diabetes and cardiovascular diseases. We also identify key contributors to the prediction, which can be further explored for their implications on electronic health records.

Establishing clinical severity for PROMIS® measures in adult patients with rheumatic diseases.

PURPOSE: Different patient-reported outcome (PRO) measures are used for rheumatic diseases (RD). The aims of this study are-(1) Identify PROMIS® domains most relevant to care of patients with RD, (2) Collect T-Score metrics in patients with RD, and (3) Identify clinically meaningful cut-points for these domains. METHODS: A convenience sample of RD patients was recruited consecutively during clinic visits, and asked to complete computer-adaptive tests on thirteen Patient-Reported Outcomes Measurement Information System (PROMIS®) instruments. Based on discussion with clinical providers, four measures were chosen to be relevant and actionable (from rheumatologists' perspective) in RD patients. Data from RD patients were used to develop clinical vignettes across a range of symptom severity. Vignettes were created based on most likely item responses at different levels on the T-score metric (mean = 50; SD = 10) and anchored at 5-point intervals (0.5 SDs). Patients with RD (N = 9) and clinical providers (N = 10) participated as expert panelists in separate one-day meetings using a modified educational standard setting method. RESULTS: Four domains (physical function, pain interferences, sleep disturbance, depression) that are actionable at the point-of-care were selected. For all domains, patients endorsed cut-points at lower levels of impairment than providers by 0.5 to 1 SD (e.g., severe impairment in physical function was defined as a T-score of 35 by patients and 25 by providers). CONCLUSIONS: We used a modified educational method to estimate clinically relevant cut-points to classify severity for PROMIS measures This allows for meaningful interpretation of PROMIS® measures in a clinical setting of RD population.

Evaluation of a family camp intervention for children with a heart transplant and their families.

Given the arduous course of heart transplantation and follow-up care, recipients and their families face complex challenges and stressors warranting supportive interventions. This study explored the impact of a family camp as an intervention of education and social support for pediatric transplant recipients and their families. A total of 49 individuals participated in this evaluation, including eight children and nine youth with heart transplants, five siblings, 19 parents, and 13 health care providers. Participants ranked and described the 3-day family camp experience. Analysis of pre/post intervention measures on knowledge, social support, and coping revealed statistically significant improvements in knowledge, social support, self-esteem, and psychological stability. Satisfaction surveys revealed the camp to be an important resource for education, family fun, and peer support among transplant recipients, their families, and the health care team. Implications and recommendations are offered for clinical and community practice.

Systemic sclerosis: a systematic review on therapeutic management from 2011 to 2014.

PURPOSE OF REVIEW: To review pharmacologic and nonpharmacologic therapies in the treatment of systemic sclerosis (SSc) from 2011 to 2014 through a systematic review. RECENT FINDINGS: Our systematic review identifies randomized controlled trials, meta-analyses, systematic reviews, case series, and observational studies which support organ-based therapy with known immunosuppressive agents, novel agents, and hematopoietic stem cell transplantation, and also includes nonpharmacologic therapies improving visceral and physical function. SUMMARY: SSc is an orphan autoimmune disorder with significant morbidity and mortality. Although there has been significant progress over the years in therapeutic options for SSc, the mainstays of treatment are organ-based and primarily symptom management. Our systematic review of the last 4 years of treatment emphasizes known treatment strategies already in practice, but also identifies new therapeutic approaches with additional biologic agents and hematopoietic stem cell transplantation.

Precision alignment of integrated optics in hybrid microsystems.

We achieve submicrometer precision in the integration of micro-optics with surface electrode ion traps. The high-precision alignment is accomplished using off-axis linear Fresnel zone plates (FZPs). Four pairs of FZPs are fabricated on the optics chip that contains the high numerical aperture microlens, a diffractive optical element (DOE). The four pairs of FZPs enable alignment in six translational and rotational degrees of freedom. Four corresponding alignment rulers are etched in the top metal layer of the ion trap, enabling quantification of misalignment. The integration of optics for efficient light delivery and the collection of fluorescence from trapped ions are key to achieving scalability in quantum information processing. An accurate and precise approach to the integration of DOEs advances the scalability of surface electrode ion traps and many other hybrid microsystems.

Designing a safe and sustainable pediatric neurosurgical practice: the English experience.

The 2001 Report of the Public Inquiry into children's heart surgery at the Bristol Royal Infirmary 1984-1995 stated that there must be standards for hospitals as a whole and that hospitals, which do not meet these standards, should not be able to offer services within the National Health Service (NHS). In 2013, agreed standards for pediatric neurosurgery were produced. Between 2001 and 2013 several key documents were published, which formed the background to the review that produced these standards:, the 'Safe and Sustainable' review. The process had the mission statement, 'Safe, sustainable and world class. Not ordinary, OK or just good enough.' In April 2013, the new commissioning structure of NHS England came into being. Clinical Reference Groups (reporting directly into the new structure) and pediatric neurosurgical operational delivery networks are taking the Safe and Sustainable pediatric neurosurgery standards and models of care into practice in England. Effective outcome data collection will allow us to assess whether these networks will improve equity of access for English children to world-class pediatric neurosurgical care and reduce the variation in outcomes seen at the present time.

Written information about retinopathy of prematurity in Aotearoa New Zealand: identification, review and opportunities for improvement.

AIMS: The aims of this research include adapting a patient information tool for whanau (extended family) Maori needs, identifying and reviewing written information provided for the retinopathy of prematurity eye examination (ROPEE) and identifying improvements to ROPEE written information. METHODS: ROPEE patient information (printed leaflets, website, app) was obtained from all tertiary neonatal intensive care units in Aotearoa New Zealand (Aotearoa). Information was reviewed using an adapted "20 good-design principles" guide and given a star rating and Flesch-Kincaid readability score to identify acceptability and usability for patients. RESULTS: Seven ROPEE information materials were reviewed and varied in alignment with the adapted good-design principles tool. Based on the adapted good-design principles, opportunities were identified in many aspects of the written information for improvement, including words and language, tone and meaning, content and design. The Flesch-Kincaid grade level reading scores ranged from 12-22 years reading age. Written information also did not use te reo Maori (Aotearoa Indigenous language) or extensively use Maori imagery. CONCLUSION: Opportunities exist to improve ROPEE whanau information, including making content more readable, understandable and visually appealing. Optimising the clinical information on ROPEE nationally for Aotearoa will support whanau decision making, and aligning written information with Maori (Indigenous peoples of Aotearoa) is a priority.

Timing of Maternal COVID-19 Vaccine and Antibody Concentrations in Infants Born Preterm.

Importance: COVID-19 vaccine-derived antibodies in pregnant people may protect infants from severe infection in the first 6 months of life via transplacental antibody transfer. Few data exist on maternally derived SARS-CoV-2 antibodies in preterm compared with full-term infants in association with vaccination timing. Objective: To compare SARS-CoV-2 anti-Spike (anti-S) antibody levels in preterm and full-term infants in the context of vaccine dose timing before delivery. Design, Setting, and Participants: This prospective cohort study enrolled pregnant individuals and collected paired maternal and cord blood samples at delivery at the University of Washington between February 1, 2021, and January 31, 2023. Participants who had received at least 2 doses of a messenger RNA COVID-19 vaccine before delivery and did not have a history of prior COVID-19 infection or detectable anti-SARS-CoV-2 nucleocapsid antibodies were included. Exposures: Timing of the last vaccine dose and preterm or full-term gestational age at delivery. Main Outcomes and Measures: Paired maternal and cord samples were tested for anti-S antibody, and linear regression was used to evaluate associations between preterm delivery and anti-S antibody levels. Covariates included timing of last dose, number of doses, insurance status, and immunosuppressing medications. Results: A total of 220 participants (median [IQR] age, 34 [32-37] years; 212 [96.4%] female) with 36 preterm and 184 full-term deliveries were studied. Before delivery, 121 persons received 2 vaccine doses and 99 persons received 3 or more vaccine doses. The geometric mean concentration of maternal anti-S antibodies was 674 (95% CI, 577-787) after 2 doses and 8159 (95% CI, 6636-10 032) after 3 or more doses (P < .001). The cord anti-S antibody geometric mean concentration was 1000 (95% CI, 874-1144) after 2 doses and 9992 (95% CI, 8381-11 914) after 3 or more doses (P < .001). After adjustment for vaccine timing and number of doses before delivery, no association was found between preterm delivery and cord anti-S antibody levels (ß = 0.44; 95% CI, -0.06 to 0.94). Conclusions and Relevance: In this prospective cohort study of pregnant individuals with preterm and full-term deliveries, receipt of 3 or more compared with 2 doses of COVID-19 vaccine before delivery resulted in 10-fold higher cord anti-S antibody levels. Maternal antibody concentration appeared more important than delivery gestational age in determining cord anti-S antibody levels. The number of doses and timing considerations for COVID-19 vaccine in pregnancy should include individuals at risk for preterm delivery.

Chapter 8: Searching for Life Beyond Earth.

The search for life beyond Earth necessitates a rigorous and comprehensive examination of biosignatures, the types of observable imprints that life produces. These imprints and our ability to detect them with advanced instrumentation hold the key to our understanding of the presence and abundance of life in the universe. Biosignatures are the chemical or physical features associated with past or present life and may include the distribution of elements and molecules, alone or in combination, as well as changes in structural components or physical processes that would be distinct from an abiotic background. The scientific and technical strategies used to search for life on other planets include those that can be conducted in situ to planetary bodies and those that could be observed remotely. This chapter discusses numerous strategies that can be employed to look for biosignatures directly on other planetary bodies using robotic exploration including those that have been deployed to other planetary bodies, are currently being developed for flight, or will become a critical technology on future missions. Search strategies for remote observations using current and planned ground-based and space-based telescopes are also described. Evidence from spectral absorption, emission, or transmission features can be used to search for remote biosignatures and technosignatures. Improving our understanding of biosignatures, their production, transformation, and preservation on Earth can enhance our search efforts to detect life on other planets.