High-dose influenza vaccine in older adults by age and seasonal characteristics: Systematic review and meta-analysis update.

This updated systematic review and meta-analysis of randomized and observational studies published up to April 2023 assessed the relative performance of high-dose inactivated influenza vaccine (HD-IIV) and standard-dose influenza vaccines (SD-IIV) against influenza-associated outcomes in older adults (≥65 years). The analysis included studies conducted over 12 influenza seasons (2009/2010 to 2019/2020, 2021/2022), including over 45 million individuals aged ≥ 65 years, and showed that HD-IIV provided significantly better protection than SD-IIV against influenza-like illness and influenza-related hospitalizations, as well as cardiovascular, cardiorespiratory, and all-cause hospitalizations. Subgroup analyses showed HD-IIV consistently provided better protection than SD-IIV against influenza outcomes across the age range (65+, 75+ 85+ years), and regardless of the predominantly circulating influenza strain and vaccine antigenic match/mismatch. Randomized studies continue to drive high-quality evidence on the effectiveness of high-dose inactivated influenza vaccine relative to SD-IIV against severe influenza outcomes in adults aged ≥ 65 years, supported by observational data.

A Systematic Narrative Review of Implementation, Processes, and Outcomes of Human Library.

First started in Denmark in 2000, Human Library (HL) has been adopted by different communities around the world. It is an innovative approach that engages "readers" from the general public to have collaborative conversations with "books" from minority or marginalized communities to learn about their lived experiences and reduce public stigma and stereotypes. While the HL is popularized, its research base and implementation structure remain limited. This systematic narrative review aims to review the HL literature to (1) summarize the design, implementation, processes, and outcomes of existing HL programs and (2) synthesize recommendations for future implementation of more effective, ethical, and sensible HL. A systematic search in eight electronic databases yielded 23 journal articles and book chapters about HL published from 2010 to 2022. The identified literature demonstrated variations in format, venue, scale, preparation, and recruitment. A wide range of books with different social identities and from different cultural groups were reported, while readers were mostly from university and school communities. Reduced prejudices and improved attitudes were reported in readers, while both readers and books reported various facets of personal growth. Future HL using implementation guidelines with clearly articulate ethical considerations and diverse rigorous research methodologies are recommended.

Efficacy and effectiveness of high-dose influenza vaccine in older adults by circulating strain and antigenic match: An updated systematic review and meta-analysis.

BACKGROUND: Influenza vaccine efficacy/effectiveness can vary from season to season due in part to the dominant circulating strains and antigenic matching. This study reviews the relative vaccine efficacy/effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared to standard-dose influenza vaccines (SD-IIV) in adults aged ≥ 65 years against influenza-associated outcomes. Additional sub-analyses of HD-IIV3 rVE were performed by the predominantly circulating influenza strain and the antigenic match or mismatch of the vaccine against the predominant circulating strains. METHODS: An updated systematic review and meta-analysis was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults aged ≥ 65 years. Results from individual seasons were extracted from the studies, and viral surveillance data were used to determine the dominant circulating strains and antigenic match for each season. Results were then stratified based on clinical outcomes and seasonal characteristics and meta-analyzed to estimate pooled rVEs of HD-IIV3. RESULTS: 15 publications were meta-analyzed after screening 1,293 studies, providing data on 10 consecutive influenza seasons and over 22 million individuals receiving HD-IIV3 in randomized and observational settings. Across all influenza seasons, HD-IIV3 demonstrated improved protection against ILI compared to SD-IIV (rVE = 15.9%, 95% CI: 4.1-26.3%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 8.4%, 95% CI: 5.7-11.0%), as well as influenza (rVE = 11.7%, 95% CI: 7.0-16.1%), pneumonia (rVE = 27.3%, 95% CI: 15.3-37.6%), combined pneumonia/influenza (rVE = 13.4%, 95% CI: 7.3-19.2%) and cardiorespiratory events (rVE = 17.9%, 95% CI: 15.0-20.8%). Reductions in mortality due to pneumonia/influenza (rVE = 39.9%, 95% CI: 18.6-55.6%) and cardiorespiratory causes (rVE = 27.7%, 95% CI: 13.2-32.0%) were also observed. Similar pooled rVEs were observed in both matched and mismatched seasons and in seasons where A/H3N2 or A/H1N1 strains were predominantly circulating. CONCLUSIONS: Evidence over 10 consecutive influenza seasons and in more than 34 million individuals aged ≥ 65 years suggests that HD-IIV3 is consistently more effective than SD-IIV at reducing influenza cases as well as influenza-associated clinical complications irrespective of circulating strain and antigenic match. A video summary of the article can be accessed via the Supplementary data link at the end of this article.

A Critical Review of Academic Literature Constructing Well-Being in Autistic Adults.

The emergence of critical autism studies has fueled efforts to interrogate how autistic people are studied and described in academic literature. While there is a call for research that promotes better well-being for autistic people, little attention has been paid to the concept of well-being itself. Just as the medical model limits critical understandings of autism in the academic literature, so too may psychological accounts of well-being limit, rather than expand, possibilities of living a good life for autistic people. The purpose of this critical review was to identify and critique how well-being in autistic adults is constructed in research. Based on a systematic search of peer-reviewed empirical research published from 2013 to 2020, we identified 63 articles that involved direct data collection with autistic adults and focused on well-being constructs such as quality of life, life satisfaction, and happiness. We examined the articles using the techniques of critical discourse analysis to discern assumptions underlying constructions of autistic well-being, with special attention to the axiological and teleological contributions of autistic perspectives in the research and writing processes. We identified several approaches through which the literature constructed autistic well-being: (1) well-being as an objective uncontested variable, (2) well-being as personal and not fixed, (3) well-being that warrants a specific measure for the autistic population, and (4) well-being as a situated account that privileges and centers autistic people's perspectives. We subject these accounts to critical analysis, pointing to how they limit and open life possibilities for autistic people. We recommend that researchers and practitioners critically reflect on how they engage autistic adults and use their input to create works that support well-being in ways that are meaningful and ethical to autistic adults, as well as do justice to changing broader narratives of autism in research and society. Lay summary: Why was this study done?: More autistic people and researchers have advocated to study autism in critical and positive ways. While it is important to promote better well-being for autistic people, little is known about what well-being actually means to them.What was the purpose of this study?: The purpose of our critical review was to identify how the concept of well-being in autistic people is understood and described in academic literature. We also critiqued how well-being research considers the input and perspectives of autistic adults.What did we do?: We systematically searched for research articles published between 2013 and 2020. We identified 63 articles that involved direct data collection with autistic adults and focused on well-being and related concepts such as quality of life, life satisfaction, and happiness. We analyzed the articles by focusing on how they used language to describe well-being in autistic adults and how they valued the data collected from these adults.What did we find?: We identified several ways that article authors described their understanding of autistic well-being: (1) well-being as an objective and uncontested object, (2) well-being is personal and can vary in nature, (3) well-being warrants a measure that considers opinions of autistic people, and (4) well-being as very specific to autistic people's subjective perspectives. We critically analyzed how these different understandings limit or open life possibilities for autistic people's well-being.How will this work help autistic people?: We recommend that researchers critically reflect on how they engage autistic adults and use their input in research. Promoting well-being needs to be meaningful and ethical to autistic adults. Research also needs to advocate for social justice to challenge how the majority in society understands or misunderstands autistic people.

"Different but connected": Participatory action research using Photovoice to explore well-being in autistic young adults.

LAY ABSTRACT: Past research has mainly focused on autistic people's deficits and poor outcomes compared to other groups of people. Little is known about their positive life experiences, and how to support them to achieve a higher quality of life. It is important to include autistic individuals in research so that they can influence how their voices are represented in a meaningful way and how the research results will be useful to them. In this study, a university researcher collaborated with 14 autistic young adults in a post-school transition program to design and run the research, collect and analyze the data, and use the results to create a presentation to the community. Specifically, the participants took photos in daily life and discussed their ideas about what a good life means to them. Results showed that these young adults described themselves as uniquely and different, but they were eager to learn and adapt. They also valued their relationships with their families, friends, and animals around them, as well as the community at large. This research shows that autistic individuals have important perspectives to share and knowledge to contribute when they are given the opportunities to participate in different aspects of research. The findings will be useful in developing services and influencing policies that promote well-being among autistic adults.

Meaning in Measurement: Evaluating Young Autistic Adults' Active Engagement and Expressed Interest in Quality-of-Life Goals.

The need for support programs and meaningful measurement of outcomes with autistic adults is growing. To date, success in autism intervention has been defined based on changes in discretely defined, observable behaviors with limited consideration of the person's experience, motivations, or the complex contexts in which these skills are used. Behavioral skill-building interventions are effective at increasing or decreasing specific behaviors, but a purely behavioral focus is not enough for meaningful improvements in adult quality of life (QoL). To reflect real-life impact, intervention and measurement must go beyond quantitative estimates of changes in skills regardless of context of use and focus on enhancing and evaluating functional outcomes and adult QoL that includes active engagement with the adult and provides rigor in qualitative evaluation. This article reports on efforts to assess active engagement of verbally fluent young autistic adults in a supported university-based residential pilot program built around self-set wellness goals for healthy, engaged, responsible, and empowered adult living. Program evaluation used an exploratory process for evaluating QoL learning, while also being open to how future work can discern participant meanings in measurement. The pilot used a mixed-methods approach to measure entry skills and interests, codetermine personal wellness goals, inform program content with participants, and measure QoL learning in terms of active engagement, expressed interest, and changes in self-appraisal of competence, confidence, and identity. Participants' QoL learning, replication of QoL learning measurement methods, and further exploration of strategies to put participant meanings in QoL learning measurement are discussed. Lay summary: Why was this study done?: This study piloted a measurement strategy for deciding what to measure and support in real-world contexts of independent living and on-campus experiences in a 3-week residential program for young autistic adults.What was the purpose of this study?: The study aimed to measure and support autistic adults' quality of life (QoL) learning in terms of the extent to which pursuing self-set wellness goals, with supports, positively impacted autistic adults' active engagement (e.g., participation in wellness activities), and expressed interest (e.g., willingness to participate).Why was this program developed?: The program was developed because more young adults on the spectrum are aging into adulthood without personalized, respectful, and meaningful supports to promote engaged adult living. We wanted to build on our experience and feedback from autistic adults, family, and partners who have engaged in weekly social engagement groups on a university campus and called for more comprehensive transition programs.What did the program do?: The project was a pilot of an on-campus program aimed at facilitating personally meaningful improvements in QoL through empowering autistic adults to act on their personal motivations, interests, and goals. It also emphasized learning through experiences in real-life contexts, in collaboration with other participants, campus resources, community members, and program staff.How did the researchers evaluate the new program?: The program team used both quantitative and qualitative methods. Quantitative methods included standard self-report tools that autistic adults used to rate their safety needs, adult self-direction skills, autism-related self-concept, priority of self-set wellness goals, and confidence in abilities to achieve and learn more about one's own wellness goals. Predetermined qualitative methods included analysis of themes from participants' narrative data from their wellness interviews with participants and open-response items from self-report tools. The program was also responsive through a preprogram wellness interview with parents, staff's field notes about of participants' behaviors, conversational interactions with participants, and team discussions. Researchers contextualized and synthesized the data into narrative case studies about each participant's wellness journey.What were the early findings and what do they add to what was already known?: Results showed that the program was able to facilitate participants' QoL learning in personal wellness goals in collaboration with campus and community resources. Participants expressed meaningful changes in their expressed interests, active engagement, and self-concept through participating in this brief residential on-campus program.What are potential weaknesses of this pilot?: Weaknesses included a short time period of 3 weeks, a small participant count of 5, and the resource-intense supports needed for the program.What are the next steps?: The next steps are to adjust the program based on participant feedback and pursue creation of a multiyear program to continue piloting the measurement and support strategies for facilitating autistic adults' active wellness engagement and self-determined independent living.How will these findings and this work help autistic adults now or in the future?: This work informs future wellness interventions for measuring and supporting autistic adults' efforts to self-determine meaningful changes to their QoL.

Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis.

BACKGROUND: Influenza is responsible for a significant disease burden annually, especially in older adults. This study reviews the relative vaccine efficacy or effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared to standard-dose influenza vaccines (SD-IIV3) in adults ≥65 against influenza-associated outcomes to inform evidence-based decision-making to shift clinical practice and standard of care in this population. METHODS: A systematic review was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults ≥65. Results from individual seasons were meta-analyzed and a random-effects model was used to estimate pooled rVEs. RESULTS: After screening 992 studies, seven studies were meta-analyzed. HD-IIV3 demonstrated better protection against ILI compared to SD-IIV3 (rVE = 19.5%; 95% CI: 8.6-29.0%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 9.1%; 95% CI: 2.4-15.3%), as well as from influenza (rVE = 17.8%; 95% CI: 8.1-26.5%), pneumonia (rVE = 24.3%, 95% CI: 13.9-33.4%), and cardiorespiratory events (rVE = 18.2%; 95% CI: 6.8-28.1%). rVE against post-influenza mortality was 22.2% (95% CI: -18.2-48.8%) and 2.5% (95% CI: -5.2-9.5%) against all-cause mortality. CONCLUSIONS: Available evidence suggests HD-IIV3 is more effective than SD-IIV3 at reducing the clinical outcomes associated with influenza infection in older adults and should be considered for routine use in the 65+ population.

ALV Integration-Associated Hypomethylation at the TERT Promoter Locus.

Avian leukosis virus (ALV) is a simple retrovirus that can induce B-cell lymphoma in chicken(s) and other birds by insertional mutagenesis. The promoter region of telomerase reverse transcriptase (TERT) has been identified as an important integration site for tumorigenesis. Tumors with TERT promoter integrations are associated with increased TERT expression. The mechanism of this activation is still under investigation. We asked whether insertion of proviral DNA perturbs the epigenome of the integration site and, subsequently, impacts the regulation of neighboring genes. DNA cytosine methylation, which generally acts to suppress transcription, is one major form of epigenetic regulation. In this study, we examine allele-specific methylation patterns of genomic DNA from chicken tumors by bisulfite sequencing. We observed that alleles with TERT promoter integrations are associated with decreased methylation in the host genome near the site of integration. Our observations suggest that insertion of ALV in the TERT promoter region may induce expression of TERT through inhibition of maintenance methylation in the TERT promoter region.

Selection for avian leukosis virus integration sites determines the clonal progression of B-cell lymphomas.

Avian leukosis virus (ALV) is a simple retrovirus that causes a wide range of tumors in chickens, the most common of which are B-cell lymphomas. The viral genome integrates into the host genome and uses its strong promoter and enhancer sequences to alter the expression of nearby genes, frequently inducing tumors. In this study, we compare the preferences for ALV integration sites in cultured cells and in tumors, by analysis of over 87,000 unique integration sites. In tissue culture we observed integration was relatively random with slight preferences for genes, transcription start sites and CpG islands. We also observed a preference for integrations in or near expressed and spliced genes. The integration pattern in cultured cells changed over the course of selection for oncogenic characteristics in tumors. In comparison to tissue culture, ALV integrations are more highly selected for proximity to transcription start sites in tumors. There is also a significant selection of ALV integrations away from CpG islands in the highly clonally expanded cells in tumors. Additionally, we utilized a high throughput method to quantify the magnitude of clonality in different stages of tumorigenesis. An ALV-induced tumor carries between 700 and 3000 unique integrations, with an average of 2.3 to 4 copies of proviral DNA per infected cell. We observed increasing tumor clonality during progression of B-cell lymphomas and identified gene players (especially TERT and MYB) and biological processes involved in tumor progression.

Pitch Perception in Tone Language-Speaking Adults With and Without Autism Spectrum Disorders.

Enhanced low-level pitch perception has been universally reported in autism spectrum disorders (ASD). This study examined whether tone language speakers with ASD exhibit this advantage. The pitch perception skill of 20 Cantonese-speaking adults with ASD was compared with that of 20 neurotypical individuals. Participants discriminated pairs of real syllable, pseudo-syllable (syllables that do not conform the phonotactic rules or are accidental gaps), and non-speech (syllables with attenuated high-frequency segmental content) stimuli contrasting pitch levels. The results revealed significantly higher discrimination ability in both groups for the non-speech stimuli than for the pseudo-syllables with one semitone difference. No significant group differences were noted. Different from previous findings, post hoc analysis found that enhanced pitch perception was observed in a subgroup of participants with ASD showing no history of delayed speech onset. The tone language experience may have modulated the pitch processing mechanism in the speakers in both ASD and non-ASD groups.

Lack of TERT Promoter Mutations in Human B-Cell Non-Hodgkin Lymphoma.

Non-Hodgkin lymphomas (NHL) are a heterogeneous group of immune cell neoplasms that comprise molecularly distinct lymphoma subtypes. Recent work has identified high frequency promoter point mutations in the telomerase reverse transcriptase (TERT) gene of different cancer types, including melanoma, glioma, liver and bladder cancer. TERT promoter mutations appear to correlate with increased TERT expression and telomerase activity in these cancers. In contrast, breast, pancreatic, and prostate cancer rarely demonstrate mutations in this region of the gene. TERT promoter mutation prevalence in NHL has not been thoroughly tested thus far. We screened 105 B-cell lymphoid malignancies encompassing nine NHL subtypes and acute lymphoblastic leukemia, for TERT promoter mutations. Our results suggest that TERT promoter mutations are rare or absent in most NHL. Thus, the classical TERT promoter mutations may not play a major oncogenic role in TERT expression and telomerase activation in NHL.

A Randomized Controlled Trial of Two Syntactic Treatment Procedures With Cantonese-Speaking, School-Age Children With Language Disorders.

PURPOSE: In this study, we aimed to evaluate the efficacy of sentence-combining (SC) and narrative-based (NAR) intervention approaches to syntax intervention using a randomized-controlled-trial design. METHOD: Fifty-two Cantonese-speaking, school-age children with language impairment were assigned randomly to either the SC or the NAR treatment arm. Seven children did not receive treatment as assigned. Intervention in both arms targeted the same complex syntactical structures. The SC group focused on sentence combination training, whereas the NAR group made use of narratives in which the target structures were embedded. Pretest and posttest performances measured using a standardized language assessment were subjected to analyses of covariance mixed-effect-model analyses of variance. RESULTS: Children in both treatment arms demonstrated significant growth after 4 months of intervention. The main effect between treatment arms and time was not significant after controlling the pretest performance, suggesting that both treatment approaches showed similar effects. The main effect of time was significant. CONCLUSIONS: This study provided evidence to support language intervention in the school years in Cantonese-speaking children. However, neither approach was shown to be more efficacious than the other. Future researchers could examine the effects of a longer treatment period and include functional outcome measures.

Camper learning and friendship at pediatric oncology camps in North America.

Children with cancer and their families often attend specialized camps (therapeutic recreation) through their cancer treatment journey, yet little is known about the effects of these camps. A qualitative cohort study was used to assess learning and friendship development by campers attending one of four pediatric oncology summer camps during 2010 in North America. Standardized perceived change questionnaires developed by the American Camp Association were administered following camp attendance. Five-hundred and eighteen campers were enrolled: 120 (age 6-9 years) and 398 (age 10 and older). The largest positive response from the younger campers was observed for the question, "At camp did you learn to look forward to trying new activities?" For the older campers' survey, the items "Becoming better at enjoying being with my friends," "Becoming better at helping my friends have a good time when they are with me," and "Becoming better at getting to know more things about my friends" were perceived to increase the most for the majority of campers compared to other questions. Items for which older campers most often perceived little change were "Becoming better at choosing people who would be good friends to be with" and "Becoming better at understanding friends' emotions." Camp helps children learn new activities as well as enjoy good times with friends. Dealing with one's own mistakes and understanding others' emotions are areas for improvement. Ultimately it is hoped that these skills gained at camp will help build coping and resiliency for children/siblings affected by pediatric cancers.

Genetic ablation of epidermal EGFR reveals the dynamic origin of adverse effects of anti-EGFR therapy.

Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs often develop a dose-limiting pruritic rash of unknown etiology. The aims of our study were to define causal associations from a clinical study of cutaneous and systemic changes in patients treated with gefitinib and use these to develop and characterize a mouse model that recapitulates the human skin rash syndrome caused by anti-EGFR therapy. We examined the patients' plasma before and after treatment with gefitinib and documented changes in chemokines and leukocyte counts associated with the extent of rash or the presence of pruritus. We established a parallel mouse model by ablating EGFR in the epidermis. These mice developed skin lesions similar to the human rash. Before lesion development, we detected increased mRNA expression of chemokines in the skin associated with early infiltration of macrophages and mast cells and later infiltration of eosinophils, T cells, and neutrophils. As the skin phenotype evolved, changes in blood counts and circulating chemokines reproduced those seen in the gefitinib-treated patients. Crossing the mutant mice with mice deficient for tumor necrosis factor-α (TNF-α) receptors, MyD88, NOS2, CCR2, T cells, or B cells failed to reverse the skin phenotype. However, local depletion of macrophages provided partial resolution, suggesting that this model can identify targets that may be effective in preventing the troublesome and dose-limiting skin response to anti-EGFR drugs. These results highlight the importance of EGFR signaling in maintaining skin immune homeostasis and identify a macrophage contribution to a serious adverse consequence of cancer chemotherapy.

Role of sentence-final particles and prosody in irony comprehension in Cantonese-speaking children with and without Autism Spectrum Disorders.

English-speaking children with Autism Spectrum Disorders (ASD) are less capable of using prosodic cues such as intonation for irony comprehension. Prosodic cues, in particular intonation, in Cantonese are relatively restricted while sentence-final particles (SFPs) may be used for this pragmatic function. This study investigated the use of prosodic cues and SFPs in irony comprehension in Cantonese-speaking children with and without ASD. Thirteen children with ASD (8;3-12;9) were language-matched with 13 typically developing (TD) peers. By manipulating prosodic cues and SFPs, 16 stories with an ironic remark were constructed. Participants had to judge the speaker's belief and intention. Both groups performed similarly well in judging the speaker's belief. For the speaker's intention, the TD group relied more on SFPs. The ASD group performed significantly poorer and did not rely on either cue. SFPs may play a salient role in Cantonese irony comprehension. The differences between the two groups were discussed by considering the literature on theory of mind.

The effects of removing the GAT domain from E. coli GMP synthetase.

E. coli GMP synthetase (GMPS) catalyzes the conversion of XMP to GMP. Ammonia, generated in the amino-terminal glutamine amidotransferase (GAT) domain, is transferred by an unknown mechanism to the ATP-pyrophosphatase (ATPP) domain, where it attacks a highly reactive adenyl-XMP intermediate, leading to GMP formation. To study the structural requirements for the activity of E. coli GMPS, we used PCR to generate a protein expression construct that contains the ATPP domain as well as the predicted dimerization domain (DD). The ATPP/DD protein is active in solution, utilizing NH (4) (+) as an NH(3) donor. Size-exclusion chromatography demonstrates a dimeric mass for the ATPP/ DD protein, providing the first evidence in solution for the structural organization of the intact GMPS. Kinetic characterization of the ATPP/DD domain protein provides evidence that the presence of the GAT domain can regulate the activity of the ATPP domain.