Are dietary inequalities among Australian adults changing? a nationally representative analysis of dietary change according to socioeconomic position between 1995 and 2011-13

Abstract Background Increasing inequalities in rates of obesity and chronic disease may be partly fuelled by increasing dietary inequalities, however very few nationally representative analyses of socioeconomic trends in dietary inequalities exist. The release of the 2011–13 Australian National Nutrition and Physical Activity Survey data allows investigation of change in dietary intake according to socioeconomic position (SEP) in Australia using a large, nationally representative sample, compared to the previous national survey in 1995. This study examined change in dietary intakes of energy, macronutrients, fiber, fruits and vegetables among Australian adults between 1995 and 2011–13, according to SEP. Methods Cross-sectional data were obtained from the 1995 National Nutrition Survey, and the 2011–13 National Nutrition and Physical Activity Survey. Dietary intake data were collected via a 24-h dietary recall (n = 17,484 adults) and a dietary questionnaire (n = 15,287 adults). SEP was assessed according to educational level, equivalized household income, and area-level disadvantage. Survey-weighted linear and logistic regression models, adjusted for age, sex/gender and smoking status, examined change in dietary intakes over time. Results Dietary intakes remained poor across the SEP spectrum in both surveys, as evidenced by high consumption of saturated fat and total sugars, and low fiber, fruit and vegetable intakes. There was consistent evidence (i.e. according to ≥2 SEP measures) of more favorable changes in dietary intakes of carbohydrate, polyunsaturated and monounsaturated fat in higher, relative to lower SEP groups, particularly in women. Intakes of energy, total fat, saturated fat and fruit differed over time according to a single SEP measure (i.e. educational level, household income, or area-level disadvantage). There were no changes in intake of total sugars, protein, fiber or vegetables according to any SEP measures. Conclusions There were few changes in dietary intakes of energy, most macronutrients, fiber, fruits and vegetables in Australian adults between 1995 and 2011–13 according to SEP. For carbohydrate, polyunsaturated and monounsaturated fat, more favorable changes in intakes occurred in higher SEP groups. Despite the persistence of suboptimal dietary intakes, limited evidence of widening dietary inequalities is positive from a public health perspective. Trial registration Clinical trials registration: ACTRN12617001045303

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis

Objective To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). Study design Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. Results Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. Conclusion Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.Peer reviewe

Parent experience with false-positive newborn screening results for cystic fibrosis

BACKGROUND: The risk of psychosocial harm in families of infants with false-positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF) is a longstanding concern. Whether well designed retrieval and confirmatory testing systems can mitigate risks remains unknown. METHODS: Using a mixed-methods cohort design, we obtained prospective self-report data from mothers of infants with FP CF NBS results 2 to 3 months after confirmatory testing at Ontario\u27s largest follow-up center, and from a randomly selected control sample of mothers of screen negative infants from the same region. Mothers completed a questionnaire assessing experience and psychosocial response. A sample of mothers of FP infants completed qualitative interviews. RESULTS: One hundred thirty-four mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%) completed questionnaires; 54 mothers of FP infants were interviewed. Selected psychosocial response measures did not detect psychosocial distress in newborns or 1 year later (P \u3e .05). Mothers recalled distress during notification of the positive result and in the follow-up testing period related to fear of chronic illness, but valued the screening system of care in mitigating concerns. CONCLUSIONS: Although immediate distress was reported among mothers of FP infants, selected psychometric tools did not detect these concerns. The NBS center from which mothers were recruited minimizes delay between notification and confirmatory testing and ensures trained professionals are communicating results and facilitating follow-up. These factors may explain the presence of minimal psychosocial burden. The screening system reflected herein may be a model for NBS programs working to minimize FP-related psychosocial harm

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Overall survival following mastectomy and breast conserving surgery with adjuvant radiotherapy for early breast cancer:meta-analysis

BackgroundBreast conserving surgery with adjuvant radiotherapy (BCS+RT) and mastectomy are currently offered as equivalent surgical options for early breast cancer based onrandomised trials dating from the 1980s. Breast cancer treatment, however has evolved and recent observational studies suggest a survival advantage for BCS+RT. A systematic review and meta-analysis was undertaken to summarise the contemporary evidence regarding survival following BCS+RT and mastectomy in women with early breast cancer. MethodsA systematic search of Medline, CENTRAL and EMBASE identified studies published 01/01/2000-18/12/2023 comparing overall survival after BCS+RT and mastectomy in patients with unilateral stage I-III breast cancer was undertaken. Studies evaluating neoadjuvant chemotherapy, rare breast cancer subtypes and studies in specific breast cancer populations were excluded. ROBINS-I was used to assess risk of bias with the overall certainty of evidence assessed using GRADE. Studies without critical risk of bias were included in a quantitative meta-analysis. Results From 11,750 abstracts, 110 eligible studies were identified, of which 29 were at critical risk of bias and excluded; 42 were excluded due to overlapping study populations. Thirty-six observational studies reported survival outcomes in 909,077 patients (362,390 mastectomy and 546,687BCS+RT). The pooled hazard ratio was 0.72 (95% 3 confidence interval 0.68–0.75, p<0.001) demonstrating improved overall survival for patients undergoing BCS+RT. The overall certainty of the evidence was very low.ConclusionThis meta-analysis provides evidence to suggest a survival advantage for women undergoing BCS+RT for early breast cancer compared with mastectomy. Although these results should be interpreted with caution, they should be shared with patients to support informed surgical decision-making

Postnatal Prediction of Gestational Age Using Newborn Fetal Hemoglobin Levels

Introduction: In many parts of the developing world procurement of antenatal gestational age estimates is not possible, challenging provision of appropriate perinatal care. This study aimed to develop a model for postnatal gestational age estimation utilizing measures of the newborn hemoglobin levels and other metabolic analyte data derived from newborn blood spot samples. Methods: We conducted a retrospective cohort analysis of 159,215 infants born January 2012–December 2014 in Ontario, Canada. Multivariable linear and logistic regression analyses were used to evaluate the precision of developed models. Results: Models derived from a combination of hemoglobin ratios and birthweight were more precise at predicting gestational age (RMSE1·23 weeks) than models limited to birthweight (RMSE1·34). Models including birthweight, hemoglobin, TSH and 17-OHP levels were able to accurately estimate gestational age to ±2 weeks in 95·3% of the cohort and discriminate ≤34 versus >34 (c-statistic, 0·98). This model also performed well in small for gestational age infants (c-statistic, 0·998). Discussion: The development of a point-of-care mechanism to allow widespread implementation of postnatal gestational age prediction tools that make use of hemoglobin or non-mass spectromietry-derived metabolites could serve areas where antenatal gestational age dating is not routinely available