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Simple Summary: Measurable residual disease monitoring is an important prognostic tool in haematological malignancies commonly performed by two modalities: flow cytometry and molecular methods. In this paper, we studied consecutive adult participants requiring flow cytometric measurable residual disease monitoring. This is one of the largest prospective Australian studies to date, providing a unique insight into the Australian context. We described five distinctive patterns associated with disease relapse and survival and also investigated correlation with molecular methods. Our results provide additional evidence that the correlation between molecular and flow cytometric methods is moderate in B-lymphoblastic leukaemia and poor in acute myeloid leukaemia. There was a strong association between flow cytometry results and relapse in acute myeloid leukaemia but less so for B-lymphoblastic leukaemia. Our novel data indicate that the pattern of change in measurable residual disease over time was associated with the risk of relapse, particularly in acute myeloid leukaemia and highlight the divergent ways measurable residual disease testing can be employed across different leukaemias. Measurable residual disease (MRD) detected by flow cytometry (FC) is well established in paediatric B- lymphoblastic leukaemia (B-ALL) and adult chronic lymphocytic leukaemia (CLL), but its utility in adult B-ALL and adult acute myeloid leukaemia (AML) is less clear. In this prospective MRD study, one of the largest in Australia to date, we examined consecutive bone marrow aspirates from adult participants with B-ALL (n = 47) and AML (n = 87) sent for FC-MRD testing at a quaternary referral hospital in Sydney. FC-MRD results were correlated to corresponding Mol-MRD testing where available and clinical outcomes at three-month intervals over 1 year. B-ALL showed a moderate positive correlation (rs = 0.401, p < 0.001), while there was no correlation between FC-MRD and Mol-MRD for AML (rs = 0.13, p = 0.237). Five FC-MRD patterns were identified which had significant associations with relapse (X2(4) = 31.17(4), p > 0.001) and survival (X2(4) = 13.67, p = 0.008) in AML, but not in B-ALL. The three-month MRD results were also strongly associated with survival in AML, while the association in B-ALL was less evident. There was a moderate correlation between FC-MRD and Mol-MRD in B-ALL but not AML. The association of FC-MRD with relapse and survival was stronger in AML than in B-ALL. Overall, these findings suggest divergent utilities of FC-MRD in AML and B-ALL. [ABSTRACT FROM AUTHOR]

Annual vaccination against influenza is the best tool to prevent deaths and hospitalizations. Regular updates of trivalent inactivated influenza vaccines (TIV) are necessary due to high mutation rates in influenza viruses. TIV effectiveness is affected by antigenic mismatches, age, previous immunity, and other host factors. Studying TIV effectiveness annually in different populations is critical. The serological responses to Southern-Hemisphere TIV and circulating influenza strains were evaluated in 2018–2020 among Brazilian volunteers, using hemagglutination inhibition (HI) assays. Post-vaccination titers were corrected to account for pre-vaccination titers. Our population achieved >83% post-vaccination seroprotection levels, whereas seroconversion rates ranged from 10% to 46%. TIV significantly enhanced antibody titers and seroprotection against all prior and contemporary vaccine and circulating strains tested. Strong cross-reactive responses were detected, especially between H1N1 subtypes. A/Singapore/INFIMH-16-0019/2016, included in the 2018 TIV, induced the poorest response. Significant titer and seroprotection reductions were observed 6 and 12 months after vaccination. Age had a slight effect on TIV response, whereas previous vaccination was associated with lower seroconversion rates and titers. Despite this, TIV induced high seroprotection for all strains, in all groups. Regular TIV evaluations, based on regional influenza strain circulation, should be conducted and the factors affecting response studied. [ABSTRACT FROM AUTHOR]

Background and objective: In 2014, a 6‐week‐long fire at the Hazelwood coal mine exposed residents in the adjacent town of Morwell to high concentrations of fine particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5). The long‐term health consequences are being evaluated as part of the Hazelwood Health Study. Methods: Approximately 3.5–4 years after the mine fire, adults from Morwell (n = 346) and the comparison town Sale (n = 173) participated in the longitudinal Respiratory Stream of the Study. Individual PM2.5 exposure was retrospectively modelled. Lung mechanics were assessed using the forced oscillation technique (FOT), utilizing pressure waves to measure respiratory system resistance (Rrs) and reactance (Xrs). Multivariate linear regression was used to evaluate associations between PM2.5 and transformed Rrs at 5 Hz, area under the reactance curve (AX5) and Xrs at 5 Hz controlling for key confounders. Results: There were clear dose–response relationships between increasing mine fire PM2.5 and worsening lung mechanics, including a reduction in post‐bronchodilator (BD) Xrs5 and an increase in AX5. A 10 μg/m3 increase in mine fire‐related PM2.5 was associated with a 0.015 (95% CI: 0.004, 0.027) reduction in exponential (Xrs5) post‐BD, which was comparable to 4.7 years of ageing. Similarly, the effect of exposure was associated with a 0.072 (0.005, 0.138) increase in natural log (lnAX5) post‐BD, equivalent to 3.9 years of ageing. Conclusion: This is the first study using FOT in adults evaluating long‐term respiratory outcomes after medium‐term ambient PM2.5 exposure to coal mine fire smoke. These results should inform public health policies and planning for future events. [ABSTRACT FROM AUTHOR]

Aims: To characterise the genetic alterations in adult primary uterine rhabdomyosarcomas (uRMSs) and to investigate whether these tumours are genetically distinct from uterine carcinosarcomas (UCSs). Methods and results: Three tumours originally diagnosed as primary adult pleomorphic uRMS were subjected to massively parallel sequencing targeting 468 cancer‐related genes and RNA‐sequencing. Mutational profiles were compared with those of UCSs (n = 57) obtained from The Cancer Genome Atlas. Sequencing data analyses were performed using validated bioinformatic approaches. Pathogenic TP53 mutations and high levels of genomic instability were detected in the three cases. uRMS1 harboured a likely pathogenic YTHDF2–FOXR1 fusion. uRMS2 harboured a PPP2R1A hotspot mutation and amplification of multiple genes, including WHSC1L1, FGFR1, MDM2, and CCNE1, whereas uRMS3 harboured an FBXW7 hotspot mutation and an ANKRD11 homozygous deletion. Hierarchical clustering of somatic mutations and copy number alterations revealed that these tumours initially diagnosed as pleomorphic uRMSs and UCSs were similar. Subsequent comprehensive pathological re‐review of the three uRMSs revealed previously unidentified minute pan‐cytokeratin‐positive atypical glands in one case (uRMS3), favouring its reclassification as UCS with extensive rhabdomyosarcomatous overgrowth. Conclusions: Adult pleomorphic uRMSs harbour TP53 mutations and high levels of copy number alterations. Our findings underscore the challenge in discriminating between uRMS and UCS with rhabdomyosarcomatous differentiation. [ABSTRACT FROM AUTHOR]

We use administrative data from the Internal Revenue Service to examine long-term impacts of childhood Medicaid eligibility expansions on outcomes in adulthood at each age from 19 to 28. Greater Medicaid eligibility increases college enrolment and decreases fertility, especially through age 21. Starting at age 23, females have higher contemporaneous wage income, although male increases are imprecise. Together, both genders have lower mortality. These adults collect less from the earned income tax credit and pay more in taxes. Cumulatively from ages 19 to 28, at a 3% discount rate, the federal government recoups 58 cents of each dollar of its "investment" in childhood Medicaid. [ABSTRACT FROM AUTHOR]

Prior to the subtraction of Section 28 from the 1988 Local Government Act in 2003, a substantial amount of research was published that specifically examined the experiences of lesbian physical education (PE) teachers. This article contributes to the existing academic literature by exploring the lives of lesbian, gay, bisexual and transsexual teachers working in a post-Section 28 school environment. Drawing on life history interviews of two lesbian PE teachers, we offer insights into how the abolition of Section 28 has affected their lives. Comparable to previous studies, both women reported feeling fearful of the consequences of identifying as lesbian and employed various strategies in order to maintain a divide between their public and private lives so as to conceal their sexual identities from colleagues, pupils and parents. However, in contrast to much of the previous literature, we found that the teachers in this study also identified with narratives of resistance. Despite being fearful of coming out at work, they nevertheless remained committed to coming out when the context is appropriate, to challenging the heteronormative symbolic order configured around the heterosexual/homosexual binary and to more proactively promoting sexual diversity and tolerance in schools. [ABSTRACT FROM AUTHOR]

Subjective cognitive decline (SCD) is the self-reported experience of worsening or more frequent confusion or memory loss within the previous 12 months and can be one of the earliest symptoms of Alzheimer's disease. Regular physical activity can contribute to the primary, secondary, and tertiary prevention of cognitive decline. At the national level, prevalence estimates of SCD by physical activity level in the United States are currently unknown. The purpose of this study is to examine the prevalence of SCD and resulting functional limitations by physical activity level among US adults aged ≥45 years. Data from 33 states and the District of Columbia participating in the 2015 Behavioral Risk Factor Surveillance System (N = 128,925) were analyzed. We estimated the prevalence of SCD (a positive response to a question about worsening or more frequent confusion or memory loss within the previous 12 months) and resulting functional limitations overall and by self-reported physical activity level based on current guidelines (i.e., active, insufficiently active, and inactive). Odds ratios were estimated using logistic regression models adjusting for respondent characteristics. Overall, 11.3% of US adults aged ≥45 years reported SCD. Prevalence of SCD increased as physical activity level decreased (active: 8.8%; insufficiently active: 11.4%; inactive: 15.7%). Among those with SCD, the prevalence of functional limitations also increased as physical activity level decreased (active: 40.5%; insufficiently active: 50.0%; inactive: 57.4%). These differences largely remained after adjusting for respondent characteristics. Findings highlight the potential public health impact nationally of efforts to promote physical activity for cognitive health. [ABSTRACT FROM AUTHOR]

Objectives: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators.Design: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process.Participants: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process.Measurements and Main Results: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization.Conclusions: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials. [ABSTRACT FROM AUTHOR]