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Background: Concussion and communication researchers have yet to study how post-concussion communication changes affect youths' daily lives. The lack of attention paid to how young people respond to communication changes during concussion recovery constitutes a significant gap in current concussion management research and practices. Aims: To explore how youth respond to the effects of post-concussion communication changes in their daily life, including (1) daily routines, (2) relationships with family members, (3) relationships with peers and (4) participation in school/work and community activities. Methods & Procedures: Five youths (16-25 years) and three family members participated in this arts-based reflexive collective case study. Ecocultural theory provided the theoretical framework for study design, data collection and analysis. Cases consist of (1) pre-interview demographic information, (2) three 60-90-min virtual interviews, (3) optional family member interviews, (4) multi-media arts-based participant-generated materials representing participants' experiences of communication change and concussion, and (5) researcher observations, discussions and reflexive journal entries. Reflexive thematic analysis was used to analyse the data. Outcomes & Results: Analysis yielded four themes that illustrate the ways youth navigated and adapted to post-concussion communication changes: (1) navigating changes in communication tasks, daily roles, and identity; (2) re-negotiating relationships and emotional reactions; (3) seeking control and learning to let go during recovery; and (4) helping youth adapt to post-concussion communication changes. Conclusions & Implications: The study findings deepen our understanding of the impact of post-concussion communication changes on youths' daily lives and underscore considerations critical to the development of communication-focused concussion education programs and interventions tailored specifically for youth.

Abstract Santa Maria and Guadalupe are neighboring cities in northern Santa Barbara County that have a lower socioeconomic profile than the county overall, are >75% Latino, and have up to 32,000 residents who identify as Indigenous, primarily Mixtec-speaking people from southern Mexico. We conducted a mixed-methods community needs assessment to identify unique health challenges and barriers that Latinx and Mixtec individuals faced. From January to April 2021, targeted and general recruitment approaches were used to recruit a convenience sample of 159 participants (74% Latinx, 72% female, mean age 41.3 years) to complete modified long- and short-form versions of a community health concerns survey. Fifty-four completed the 40-item form and 102 completed the 19-item form. Of these, 24 individuals who expressed interest in further participation took part in structured, open-ended interviews. Among the key issues raised in surveys and interviews were housing, healthcare, and access to recreational resources. However, perspectives and priorities differed depending on the form of data collection (closed-ended survey vs. open-ended interview). For example, interviews echoed survey respondents’ dissatisfaction regarding lack of safe and affordable housing but added perspective on housing conditions and vulnerability to landlords’ decisions. In interviews, expanding existing resources and mobilizing as a community were noted as potential solutions; existing policies, language, and lack of interest by those in power were raised as significant barriers. Our assessment suggests that Santa Maria and Guadalupe communities face concerns about housing, healthcare, and access to recreational resources. Government, community, and healthcare sectors should focus on addressing these basic health needs.

Abstract Tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global public health problem, resulting in > 1 million deaths each year. Drug resistance (DR), including the multi-drug form (MDR-TB), is challenging control of the disease. Whilst many DR mutations in the Mtb genome are known, analysis of large datasets generated using whole genome sequencing (WGS) platforms can reveal new variants through the assessment of genotype-phenotype associations. Here, we apply tree-based ensemble methods to a dataset comprised of 35,777 Mtb WGS and phenotypic drug-susceptibility test data across first- and second-line drugs. We compare model performance across models trained using mutations in drug-specific regions and genome-wide variants, and find high predictive ability for both first-line (area under ROC curve (AUC); range 88.3–96.5) and second-line (AUC range 84.1–95.4) drugs. To aggregate information from low-frequency variants, we pool mutations by functional impact and observe large improvements in predictive accuracy (e.g., sensitivity: pyrazinamide + 25%; ethionamide + 10%). We further characterise loss-of-function mutations observed in resistant phenotypes, uncovering putative markers of resistance (e.g., ndh 293dupG, Rv3861 78delC). Finally, we profile the distribution of known DR-associated single nucleotide polymorphisms across discretised minimum inhibitory concentration (MIC) data generated from phenotypic testing (n = 12,066), and identify mutations associated with highly resistant phenotypes (e.g., inhA − 779G > T and 62T > C). Overall, our work demonstrates that applying machine learning to large-scale WGS data is useful for providing insights into predicting Mtb binary drug resistance and MIC phenotypes, thereby potentially assisting diagnosis and treatment decision-making for infection control.

Abstract Tuberculosis (TB) remains one of the leading infectious disease killers in the world. The ongoing development of novel anti-TB medications has yielded potent compounds that often target single sites with well-defined mechanisms of action. However, despite the identification of resistance-associated mutations through target deconvolution studies, comparing these findings with the diverse Mycobacterium tuberculosis populations observed in clinical settings is often challenging. To address this gap, we constructed an open-access database encompassing genetic variations from > 50,000 clinical isolates, spanning the entirety of the M. tuberculosis protein-encoding genome. This resource offers a valuable tool for investigating the prevalence of target-based resistance mutations in any drug target within clinical contexts. To demonstrate the practical application of this dataset in drug discovery, we focused on drug targets currently undergoing phase II clinical trials. By juxtaposing genetic variations of these targets with resistance mutations derived from laboratory-adapted strains, we identified multiple positions across three targets harbouring resistance-associated mutations already present in clinical isolates. Furthermore, our analysis revealed a discernible correlation between genetic diversity within each protein and their predicted essentiality. This meta-analysis, openly accessible via a dedicated dashboard, enables comprehensive exploration of genetic diversity pertaining to any drug target or resistance determinant in M. tuberculosis.

Abstract Background Anopheles melas is an understudied malaria vector with a potential role in malaria transmission on the Bijagós Archipelago of Guinea-Bissau. This study presents the first whole-genome sequencing and population genetic analysis for this species from the Bijagós. To our knowledge, this also represents the largest population genetic analysis using WGS data from non-pooled An. melas mosquitoes. Methods WGS was conducted for 30 individual An. melas collected during the peak malaria transmission season in 2019 from six different islands on the Bijagós Archipelago. Bioinformatics tools were used to investigate the population structure and prevalence of insecticide resistance markers in this mosquito population. Results Insecticide resistance mutations associated with pyrethroid resistance in Anopheles gambiae s.s. from the Bijagós were absent in the An. melas population, and no signatures of selective sweeps were identified in insecticide resistance-associated genes. Analysis of structural variants identified a large duplication encompassing the cytochrome-P450 gene cyp9k1. Phylogenetic analysis using publicly available mitochondrial genomes indicated that An. melas from the Bijagós split into two phylogenetic groups because of differentiation on the mitochondrial genome attributed to the cytochrome C oxidase subunits COX I and COX II and the NADH dehydrogenase subunits 1, 4, 4L and 5. Conclusions This study identified an absence of insecticide-resistant SNPs common to An. gambiae in the An. melas population, but did identify structural variation over insecticide resistance-associated genes. Furthermore, this study presents novel insights into the population structure of this malaria vector using WGS analysis. Additional studies are required to further understand the role of this vector in malaria transmission. Graphical abstract

Abstract. Background. Upper tract urothelial carcinoma (UTUC) is an aggressive disease with a high progression rate. The standardmanagement for this disease is nephroureterectomy. Nephron sparing nonradical surgery is an alternative therapeutic approach. In men with limited life expectancy, the potential harm of UTUC progression must be weighed against surgical morbidity and mortality, and thus, more conservative approaches may be selected. This study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized UTUC. Materials and methods. A search was conducted in the Surveillance, Epidemiology, and End Results database for patients older than 80 years who were diagnosed with localized (T1–2N0M0) cancer in the renal pelvis or ureter as the only malignancy from 2004 to 2015. Patients were divided into 3 therapeutic groups: no surgery, local intervention (ie, local tumor excision or segmented ureterectomy), and radical surgery (nephroureterectomy). Demographic and cancer-related parameter data were collected. Logistic regression analysis was conducted to investigate predictors for surgical treatment. Kaplan-Meier curves and Cox regression were used to analyze survival outcomes. Results. Data from 774 patients were analyzed, including 205 in the no-surgery group, 181 in the local intervention group, and 388 in the radical surgery group. Older, African American patients with T1 stage disease were less likely to receive surgical treatment. Among surgically treated patients, renal pelvic tumors, and high-grade and T2 stage disease were associated with radical resection. Surgically treated patients had a longer median overall survival (OS) than in those treated nonsurgically (13, 35, and 47 months in no-surgery, local intervention, and radical surgery groups, respectively; p < 0.001). Although surgically treated patients demonstrated higher 5-year OS (8.8% [no surgery], 23.2% [local intervention], and 23.5% [radical surgery], p < 0.001) and 5-year disease-specific survival (DSS) (41.0%[no surgery], 69.1%[local intervention], and 72.9%[radical surgery]; p < 0.001) than in those treated nonsurgically, no significant differences were found between the local intervention and radical surgery groups (p > 0.05). Based on multivariate Cox regression analysis, surgical treatments, including both nonradical and radical resection, were independently associated with improved OS and DSS after controlling for age, marital status, tumor grade, and radiation status. Conclusions. Patients older than 80 years with localized UTUC who undergo surgery demonstrate longer survival. Radical and nonradical resections seemto have similar OS and DSS outcomes. Thus, when clinically indicated in this population, a more conservative surgical approach may be reasonable.

Abstract The Philippines is a high-incidence country for tuberculosis, with the increasing prevalence of multi- (MDR-TB) and extensively-drug (XDR-TB) resistant Mycobacterium tuberculosis strains posing difficulties to disease control. Understanding the genetic diversity of circulating strains can provide insights into underlying drug resistance mutations and transmission dynamics, thereby assisting the design of diagnostic tools, including those using next generation sequencing (NGS) platforms. By analysing genome sequencing data of 732 isolates from Philippines drug-resistance survey collections spanning from 2011 to 2019, we found that the majority belonged to lineages L1 (531/732; 72.5%) and L4 (European-American; n = 174; 23.8%), with the Manila strain (L1.2.1.2.1) being the most prominent (475/531). Approximately two-thirds of isolates were found to be at least MDR-TB (483/732; 66.0%), and potential XDR-TB genotypic resistance was observed (3/732; 0.4%), highlighting an emerging problem in the country. Genotypic resistance was highly concordant with laboratory drug susceptibility testing. By finding isolates with (near-)identical genomic variation, five major clusters containing a total of 114 isolates were identified: all containing either L1 or L4 isolates with at least MDR-TB resistance and spanning multiple years of collection. Closer inspection of clusters revealed transmission in prisons, some involving isolates with XDR-TB, and mutations linked to third-line drug bedaquiline. We have also identified previously unreported mutations linked to resistance for isoniazid, rifampicin, ethambutol, and fluoroquinolones. Overall, this study provides important insights into the genetic diversity, transmission and circulating drug resistance mutations of M. tuberculosis in the Philippines, thereby informing clinical and surveillance decision-making, which is increasingly using NGS platforms.

Abstract Background Addressing Patient Reported Outcomes (PROs) is essential for patient-centred care, shared decision making and improved health outcomes. Value-based health care systems in New South Wales (NSW) have a growing focus on collecting and using PROs that matter most to patients to improve their healthcare outcomes. Developing oral health patient reported outcomes measures (OH-PROM) is a first step towards value-based oral health care. This paper describes the development process of an adult and child OH-PROM tool that can be piloted for NSW public dental patients. Methods An expert panel was assembled to undertake a systematic process of developing OH-PROMs for NSW Health. Key methodological considerations included: (1) forming an expert panel to specify the target population and context of implementation, (2) rapid literature review and environmental scan to identify existing validated OH-PROM tools for adults and children. (3) consensus gathering with the expert panel (4) consumer feedback, and (5) finalisation of the tool for electronic oral health record (eOHR) integration to establish a set of questions, that were relevant, context-appropriate, and important to oral healthcare outcomes for patients using public dental services. Results The panel considered a total of 59 questions from two child (15), and four adult (44) Oral Health Related Quality of Life (OHRQoL) questionnaires used to collect OH-PROMs. These questions were mapped to the four key dimensions of OHRQoL for OH-PROMs: Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact. The consensus resulted in seven questions that aligned with these four dimensions to form two new NSW OH-PROM tools: one for adults and one for children. The tools were tested with consumers for understandability and usefulness before being incorporated into the electronic oral health record system, in readiness for future pilot testing. Conclusion The process for developing new OH-PROMs for NSW public dental services took a pragmatic approach that combined literature appraisal, expert consensus, and consumer consultation. Future work will assess the implementation of the OH-PROM tool and test its validity for broader use as an outcome measure for value-based oral healthcare.

Purpose: The aim of this paper is to outline the collaborative approach used to craft national learning standards for tertiary programs in the field of environment and sustainability in Australia. The field of environment and sustainability is broad and constituted by diverse stakeholders. As such, articulating a common set of learning standards presents challenges. Design/methodology/approach: The authors developed and used a staged collaborative curriculum design methodology to engage more than 250 stakeholders in tertiary environmental education, including discipline scholars, students, professional associations and employers and other environmental educators. The approach was adaptive, to ensure underrepresented stakeholders' perspectives were welcomed and recognised. The project was commissioned by the Australian Council of Environmental Deans and Directors (ACEDD) and funded by the Federal Government's Office for Learning and Teaching. Findings: The collaborative approach developed and used for this work facilitated an inclusive process that valued diversity of perspectives, rather than marginalise diversity in favour of a perspective representing a minimum level of agreement. This is reflected in the standards themselves, and is evidenced by participant feedback, piloting of the standards and their subsequent application at multiple universities. Achieving this required careful planning and facilitation, to ensure a democratisation of the stakeholder consultation process, and to build consensus in support of the standards. Endorsement by ACEDD formalised the standards' status. Originality/value: Collaborative curriculum design offered the opportunity to foster a shared sense of common purpose amongst diverse environmental education stakeholders. This approach to curriculum design is intensive and generative but uncommon and may be usefully adapted and applied in other contexts. The authors note one subsequent instance where the approach has been further developed and applied in transforming a generalist science program, suggesting the methodology used in this case may be applied across other contexts, albeit with appropriate adjustments: the authors offer it here in the spirit of supporting others in their own complex curriculum design challenges.

Transparency in the reporting of empirical studies is foundational to a credible knowledge base. Higher levels of transparency, in addition to clarity in writing, also make research more accessible to a diverse readership. Previous research reviewed how transparently reported qualitative, interview-based, studies were in contemporary technology education research (Buckley et al. in Int J Technol Des Educ, 2021a. https://doi.org/10.1007/s10798-021-09695-1). The results illustrated that no article was fully transparent and that authors tended to be less transparent in some areas, such as the management of power imbalances and a saturation point, than in others, such as the methodology adopted and research setting. This article presents a similar study, however the focus of the investigation was on contemporary quantitative technology education research. An analysis of 46 articles revealed again that no article was fully transparent and that authors tended to be more transparent in some areas than others. Interestingly, the areas where authors or quantitative research tended to be more or less transparent were similar to the areas in which authors of qualitative research tended to be more or less transparent. These results have use in supporting researchers in the clear and transparent reporting of the empirical work and could be useful in the development of guides or support material for academic writing.

To help guide school mental health policy and practice, we evaluated patterns of mental health help-seeking across lifetime adversity among sixth-grade adolescents. An ethnically/socioeconomically diverse sample of sixth-graders (N = 751) self-completed assessments of help-seeking and indicators of lifetime adversities: violence victimization, poverty, parent loss/divorce, mental illness/substance abuse at home, and stressors related to social identity. Logistic regression models adjusting for family/personal factors examined adversity factors on help-seeking outcomes overall and across subgroups with mental health perceived problems and high-symptoms. Overall, odds increased between perceived problem and formal service use, poverty and formal service/school counselor use, and high-symptoms/victimization and talking to a friend (p < 0.05). Among those with perceived problems, odds increased between mental illness/substance abuse at home and formal service use, victimization and talking to a friend, and poverty and school counselor use (p < 0.05). Among those with no mental health problems, odds increased between victimization and formal service/school counselor use, and poverty and formal service use (p < 0.05). No significant patterns were observed in the high-symptom subgroup. Understanding how adversity shapes help-seeking can help guide school mental health policies and practices. Study findings point to areas for expansion of supports for students with adversity to create a mental health safety net and help mitigate future risk.

Airway macrophages (AM) are the predominant immune cell in the lung and play a crucial role in preventing infection, making them a target for host directed therapy. Macrophage effector functions are associated with cellular metabolism. A knowledge gap remains in understanding metabolic reprogramming and functional plasticity of distinct human macrophage subpopulations, especially in lung resident AM. We examined tissue-resident AM and monocyte-derived macrophages (MDM; as a model of blood derived macrophages) in their resting state and after priming with IFN-γ or IL-4 to model the Th1/Th2 axis in the lung. Human macrophages, regardless of origin, had a strong induction of glycolysis in response to IFN-γ or upon stimulation. IFN-γ significantly enhanced cellular energetics in both AM and MDM by upregulating both glycolysis and oxidative phosphorylation. Upon stimulation, AM do not decrease oxidative phosphorylation unlike MDM which shift to ‘Warburg’-like metabolism. IFN-γ priming promoted cytokine secretion in AM. Blocking glycolysis with 2-deoxyglucose significantly reduced IFN-γ driven cytokine production in AM, indicating that IFN-γ induces functional plasticity in human AM, which is mechanistically mediated by glycolysis. Directly comparing responses between macrophages, AM were more responsive to IFN-γ priming and dependent on glycolysis for cytokine secretion than MDM. Interestingly, TNF production was under the control of glycolysis in AM and not in MDM. MDM exhibited glycolysis-dependent upregulation of HLA-DR and CD40, whereas IFN-γ upregulated HLA-DR and CD40 on AM independently of glycolysis. These data indicate that human AM are functionally plastic and respond to IFN-γ in a manner distinct from MDM. These data provide evidence that human AM are a tractable target for inhalable immunomodulatory therapies for respiratory diseases.

Despite marked advancements in the recognition and diagnosis of spontaneous coronary artery dissection (SCAD) over the past decade, knowledge of the basic pathophysiologic mechanisms of disease, contributing factors, and treatment continue to be poorly understood. We describe significant research gaps in our knowledge of SCAD and introduce strategies including the role of patient advocacy, independent registries, and creation of diverse centers of excellence to bridge the gap in clinical care, research, and outcomes. Lastly, we introduce an innovative patient-centered clinical care and research framework established through the SCAD Alliance and International Spontaneous Coronary Artery Dissection registry as a model for advancing knowledge of SCAD.

Atmospheric deposition of nitrogen (N) and sulfur (S) alter tree demographic processes via changes in nutrient pools, soil acidification, and biotic interactions. Previous work established tree growth and survival response to atmospheric N and S deposition in the conterminous United States (CONUS) data by species; however, it was not possible to evaluate regional variation in response using that approach. In this study, we develop species- and region-specific relationships for growth and survival responses to N and S deposition for roughly 140 species within spatially demarcated regions of the U.S. We calculated responses to N and S deposition separately for 11 United States Forest Service (USFS) Divisions resulting in a total of 241 and 268 species × Division combinations for growth and survival, respectively. We then assigned these relationships into broad categories of vulnerability and used ordinal logistic regressions to explore the covariates associated with vulnerability in growth and survival to N and S deposition. As with earlier studies, we found growth and survival responses to air pollution differed by species; but new to this study, we found 45%−70% of species responses also varied spatially across regions. The regional variation in species responses was not simply related to atmospheric N and S deposition, but was also associated with regional effects from precipitation, soil pH, mycorrhizal association, and deciduousness. A large amount of the variance remained unexplained (total variation explained ranged from 6.8%−13.8%), suggesting that these or additional factors may operate at finer spatial scales. Taken together, our results demonstrate that regional variation in tree species' response has significant implications for setting critical load targets, as critical loads can now be tailored for specific species at management-relevant scales.

Objective Protocol to explore what is known about communication between critical care providers and patients and families from culturally and linguistically diverse backgrounds (defined as people who are either from minority ethnic groups, non-English-speaking backgrounds who may have diverse cultural, linguistic, spiritual and religious affiliations and opinions) about death, dying, end-of-life care and organ donation in the intensive care unit (ICU).Introduction Patients from culturally and linguistically diverse backgrounds experience barriers to optimised care when admitted to the ICU. These barriers appear to derive from differences in language, cultural, societal and ethical expectations between patients, their families and healthcare professionals. These barriers may significantly impact the delivery of end-of-life care to patients from culturally and linguistically diverse backgrounds. Therefore, this has the potential for inadequate management of medical, psychological and existential distress.Inclusion criteria Studies of all designs reporting for adult (age ≥18 years) patients and family members from culturally and linguistically diverse backgrounds at end-of-life in the ICU setting will be included. Studies that report results for patients aged

In this paper, we analyse the introduction of peer mentors into timetabled classes to understand how in-class mentoring supports students' learning. The peer mentors in this study are high-achieving students who previously completed the same course and who were hired and trained to facilitate Peer Assisted Study Sessions (PASS). PASS gives students the opportunity to deepen their understanding through revision and active learning and are typically held outside of class time. In contrast, our trial embedded peer mentors into classes for a large ([approximately]250 students) first-year workshop-based course. We employed a participatory action research methodology to facilitate the peer mentors' cocreation of the research process. Data sources include peer mentors' journal entries, student cohort data, and a focus group with teaching staff. We found that during face-to-face workshops, peer mentors role-modelled ideal student behaviour (e.g., asking questions) rather than acting as additional teachers, and this helped students to better understand how to interact effectively in class. The identity of embedded peer mentors is neither that of teachers nor of students, and it instead spans aspects of both as described using a three-part schema comprising (i) identity, (ii) associated roles, and (iii) associated practices. As we moved classes online mid-semester in response to the COVID-19 pandemic, mentors' identities remained stable, but mentors adjusted their associated roles and practices, including through the technical aspects of their engagement with students. This study highlights the benefits of embedding mentors in classrooms on campus and online.